Science.gov

Sample records for dbcg trial 89b

  1. Cosmetic outcome and breast morbidity in breast-conserving treatment--results from the Danish DBCG-82TM national randomized trial in breast cancer.

    PubMed

    Johansen, Jørgen; Overgaard, Jens; Rose, Carsten; Engelholm, Svend Aage; Gadeberg, Carl C; Kjaer, Mogens; Kamby, Claus; Juul-Christensen, Jens; Blichert-Toft, Mogens; Overgaard, Marie

    2002-01-01

    A total of 266 recurrence-free breast cancer patients from the randomized DBCG-82TM breast conservation trial were called in for a follow-up investigation to study the impact of surgical and radiation treatment factors on the cosmetic and functional outcome after breast conservation. The patients were interviewed and examined after a median follow-up time of 6.6 years, and 194 of them (73%) regarded the cosmetic result as excellent or good. Morbidity assessments showed that breast fibrosis, skin telangiectasia, and breast retraction were significantly associated with a less satisfactory cosmetic result. On univariate analysis, it was found that treatment with a direct anterior electron field produced more morbidity and inferior cosmetic outcomes compared with tangential photon treatment, while increasing breast size was associated with increased breast retraction and breast fibrosis. Treatment characteristics that emerged as independent prognostic factors of a poor cosmetic outcome on multivariate analysis were the use of a direct anterior electron field (OR = 2.15, CI 1.25-3.70) and adjuvant systemic therapy (OR = 2.13, 1.22-3.71). A significant but relatively low level of concordance was found between the patients' and the clinician's evaluations of cosmetic results but self-assessments of breast morbidity and psychological distress were significantly related to the observed treatment-induced side effects after breast-conserving treatment, indicating that subjective perceptions and observations as reported by the patients are relevant for the identification of treatment factors that impact on normal tissue reactions.

  2. Danish Breast Cancer Cooperative Group--DBCG: History, organization, and status of scientific achievements at 30-year anniversary.

    PubMed

    Blichert-Toft, Mogens; Christiansen, Peer; Mouridsen, Henning T

    2008-01-01

    DBCG (Danish Breast Cancer Cooperative Group) constitutes a multidisciplinary organization established in 1975 by the Danish Surgical Society. The purpose involves first and foremost a nation-wide standardization of breast cancer treatment based on novel therapeutic principles, collaboration between experts handling diagnostic work-up, surgery, radiotherapy, medical oncology, and basic research, and, further, complete registration of relevant clinical data in a national data base attached to DBCG. Data are processed by the Secretariat personnel composed of statisticians, data managers, and data secretaries making current analyses of outcome results feasible. DBCG is run by the Executive Committee consisting of expert members appointed by their respective society. From 1978 the DBCG project gained widely accession from participating units, and since then nearly all newly diagnosed breast cancer incident cases are reported and registered in the national data base. Today, the data base includes approximately 80 000 incidents of primary breast cancer. Annually, the Secretariat receives roughly 1.5 million parameters to be entered into the data base. Over time DBCG has generated seven treatment programmes including in situ lesions and primary invasive breast cancer. Probands are subdivided into risk groups based on a given risk pattern and allocated to various treatment programmes accordingly. The scientific initiatives are conducted in the form of register- and cohort analysis or randomized trials in national or international protocolized settings. Yearly, about 4 000 new incident cases of primary invasive breast cancer and about 200 in situ lesions enter the national programmes. Further, about 600 women with hereditary disposition of breast cancer are registered and evaluated on a risk scale. The main achievements resulted in a reduction of relative risk of death amounting up to 20% and increased 5-year overall survival ascending from 60% to roughly 80%. This article

  3. Three WASP-South Transiting Exoplanets: WASP-74b, WASP-83b, and WASP-89b

    NASA Astrophysics Data System (ADS)

    Hellier, Coel; Anderson, D. R.; Collier Cameron, A.; Delrez, L.; Gillon, M.; Jehin, E.; Lendl, M.; Maxted, P. F. L.; Pepe, F.; Pollacco, D.; Queloz, D.; Ségransan, D.; Smalley, B.; Smith, A. M. S.; Southworth, J.; Triaud, A. H. M. J.; Turner, O. D.; Udry, S.; West, R. G.

    2015-07-01

    We report the discovery of three new transiting hot Jupiters by WASP-South together with the TRAPPIST photometer and the Euler/CORALIE spectrograph. WASP-74b orbits a star of V = 9.7, making it one of the brighter systems accessible to southern telescopes. It is a 0.95MJup planet with a moderately bloated radius of 1.5 {R}{Jup} in a 2 day orbit around a slightly evolved F9 star. WASP-83b is a Saturn-mass planet at 0.3 {M}{Jup} with a radius of 1.0 {R}{Jup}. It is in a 5 day orbit around a fainter (V = 12.9) G8 star. WASP-89b is a 6 MJup planet in a 3 day orbit with an eccentricity of e = 0.2. It is thus similar to massive, eccentric planets such as XO-3b and HAT-P-2b, except that those planets orbit F stars whereas WASP-89 is a K star. The V = 13.1 host star is magnetically active, showing a rotation period of 20.2 days, while star spots are visible in the transits. There are indications that the planet’s orbit is aligned with the stellar spin. WASP-89 is a good target for an extensive study of transits of star spots.

  4. Adjuvant chemotherapy in early breast cancer.

    PubMed

    Ejlertsen, Bent

    2016-05-01

    With long-term follow-up, the DBCG 77B trial demonstrates that oral single-agent cyclophosphamide significantly reduces the risk of recurrence and mortality as compared with no systemic therapy in pre-menopausal patients with high-risk early breast cancer. DBCG 77B is the only randomised trial assessing single-agent cyclophosphamide; and a second comparison suggests that its benefits are comparable to what may be achieved by classic CMF. The lack of benefits from adding methotrexate and fluorouracil to cyclophosphamide paved the way for combining cyclophosphamide with anthracyclines and later taxanes. DBCG 89D showed an incremental benefit in DFS and OS from substituting methotrexate with epirubicin. The advantage of anthracycline-containing three-drug combinations over CMF was confirmed by others and in the individual-patient EBCTCG meta-analysis, while standard AC or EC for four cycles not was superior to classic CMF. A further reduction in breast cancer mortality appeared in the EBCTCG meta-analysis from the addition of a taxane to a standard AC, while the substitution of cycles or drugs with a taxane was not associated with a reduction in mortality. No apparent benefit was observed in an early analysis of the DBCG 82C evaluating the addition of CMF to tamoxifen in post-menopausal high-risk breast cancer patients. Apart from menopausal status, the two trials had identical selection criteria, and the differences in outcome warranted a long-term follow-up of the 82C trial. After ten years of follow-up, CMF in the DBCG 82C was associated with a significant improvement in DFS; but even with 24 years of follow-up, mortality was not significantly improved. The diversity in outcome from the 77C and the 82B trials triggered further studies. The 77B trial used classic CMF with oral cyclophospamide, while a four-weekly intravenous CMF regimen was used in the 82B and C trials, and a three-weekly CMF regimen was used in the succeeding 89B and D trials. The outcome following

  5. Does timing of adjuvant chemotherapy influence the prognosis after early breast cancer? Results of the Danish Breast Cancer Cooperative Group (DBCG).

    PubMed

    Cold, S; Düring, M; Ewertz, M; Knoop, A; Møller, S

    2005-09-19

    The purpose of this study was to examine the effect on survival of delaying the start of adjuvant chemotherapy for early breast cancer for up to 3 months after surgery. In the nation-wide clinical trials of the Danish Breast Cancer Cooperative Group, 7501 breast cancer patients received chemotherapy within 3 months of surgery between 1977 and 1999: 352 with classical cyclofosfamide, metotrexate and 5-fluorouracil (CMF); 6065 with CMF i.v. and 1084 with cyclofosfamide, epirubicin and 5-fluorouracil. For the analysis, the time between surgery and the start of chemotherapy was divided into four strata (1-3, 4, 5 and 6-13 weeks). The results show that within the three groups of chemotherapy, there was an even distribution of known prognostic factors across the four strata of initiation of chemotherapy. There was no pattern indicating a benefit from early start of chemotherapy. No significant interactions were found for subgroups of patients with a poorer prognosis (many involved lymph nodes, high-grade malignancies or hormone receptor negative disease). In conclusion, we have found no evidence for a survival benefit due to early initiation of adjuvant chemotherapy within the first 2-3 months after surgery.

  6. Does timing of adjuvant chemotherapy influence the prognosis after early breast cancer? Results of the Danish Breast Cancer Cooperative Group (DBCG)

    PubMed Central

    Cold, S; Düring, M; Ewertz, M; Knoop, A; Møller, S

    2005-01-01

    The purpose of this study was to examine the effect on survival of delaying the start of adjuvant chemotherapy for early breast cancer for up to 3 months after surgery. In the nation-wide clinical trials of the Danish Breast Cancer Cooperative Group, 7501 breast cancer patients received chemotherapy within 3 months of surgery between 1977 and 1999: 352 with classical cyclofosfamide, metotrexate and 5-fluorouracil (CMF); 6065 with CMF i.v. and 1084 with cyclofosfamide, epirubicin and 5-fluorouracil. For the analysis, the time between surgery and the start of chemotherapy was divided into four strata (1–3, 4, 5 and 6–13 weeks). The results show that within the three groups of chemotherapy, there was an even distribution of known prognostic factors across the four strata of initiation of chemotherapy. There was no pattern indicating a benefit from early start of chemotherapy. No significant interactions were found for subgroups of patients with a poorer prognosis (many involved lymph nodes, high-grade malignancies or hormone receptor negative disease). In conclusion, we have found no evidence for a survival benefit due to early initiation of adjuvant chemotherapy within the first 2–3 months after surgery. PMID:16136052

  7. Clinical Trials

    MedlinePlus

    ... Sponsors Why Are They Important How Do They Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites What Are Clinical ...

  8. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study answers scientific ... screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...

  9. Clinical Trials

    MedlinePlus

    ... existing treatments. Some may study new forms of psychotherapy (talk therapy). Others may study a combination of ... period. In trials that test new forms of psychotherapy, one group may be randomly assigned to a ...

  10. Stroke Trials Registry

    MedlinePlus

    ... News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions Sponsors ... a clinical trial near you Welcome to the Stroke Trials Registry Our registry of clinical trials in ...

  11. The Trial

    ERIC Educational Resources Information Center

    Bryant, Jen

    2004-01-01

    Growing up in Flemington, New Jersey, put Jen Bryant in the heart of the lore behind the Lindbergh baby kidnapping. Family stories of the events of the day and extensive research led to "The Trial," a novel in verse. The first several parts of this novel are included here.

  12. Clinical Trials

    MedlinePlus

    ... your information private 5. What happens when the study ends The Possible Risks and Benefits The trial may provide treatments or screenings, but there is no promise that your health will get better. The medicine, test, or treatment may not work for you. 6. The benefits of the treatments ...

  13. Trial Watch

    PubMed Central

    Galluzzi, Lorenzo; Vacchelli, Erika; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zucman-Rossi, Jessica; Zitvogel, Laurence; Kroemer, Guido

    2012-01-01

    Since the advent of hybridoma technology, dating back to 1975, monoclonal antibodies have become an irreplaceable diagnostic and therapeutic tool for a wide array of human diseases. During the last 15 years, several monoclonal antibodies (mAbs) have been approved by FDA for cancer therapy. These mAbs are designed to (1) activate the immune system against tumor cells, (2) inhibit cancer cell-intrinsic signaling pathways, (3) bring toxins in the close proximity of cancer cells, or (4) interfere with the tumor-stroma interaction. More recently, major efforts have been made for the development of immunostimulatory mAbs that either enhance cancer-directed immune responses or limit tumor- (or therapy-) driven immunosuppression. Some of these antibodies, which are thought to facilitate tumor eradication by initiating or sustaining a tumor-specific immune response, have already entered clinical trials. In this Trial Watch, we will review and discuss the clinical progress of the most important mAbs that are have entered clinical trials after January 2008. PMID:22720209

  14. Trial watch

    PubMed Central

    Galluzzi, Lorenzo; Senovilla, Laura; Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido

    2012-01-01

    Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DC-based anticancer vaccines are capable of activating tumor-specific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DC-based therapeutic vaccine (sipuleucel-T, Provenge®) for use in patients with asymptomatic or minimally symptomatic metastatic hormone-refractory prostate cancer. Intense research efforts are currently dedicated to the identification of the immunological features of patients that best respond to DC-based anticancer vaccines. This knowledge may indeed lead to personalized combination strategies that would extend the benefit of DC-based immunotherapy to a larger patient population. In addition, widespread enthusiasm has been generated by the results of the first clinical trials based on in vivo DC targeting, an approach that holds great promises for the future of DC-based immunotherapy. In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating DC-based interventions for cancer therapy. PMID:23170259

  15. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Cremer, Isabelle; Henrik ter Meulen, Jan; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Toll-like receptors (TLRs) are an evolutionarily conserved group of enzymatically inactive, single membrane-spanning proteins that recognize a wide panel of exogenous and endogenous danger signals. Besides constituting a crucial component of the innate immune response to bacterial and viral pathogens, TLRs appear to play a major role in anticancer immunosurveillance. In line with this notion, several natural and synthetic TLR ligands have been intensively investigated for their ability to boost tumor-targeting immune responses elicited by a variety of immunotherapeutic and chemotherapeutic interventions. Three of these agents are currently approved by the US Food and Drug Administration (FDA) or equivalent regulatory agencies for use in cancer patients: the so-called bacillus Calmette-Guérin, monophosphoryl lipid A, and imiquimod. However, the number of clinical trials testing the therapeutic potential of both FDA-approved and experimental TLR agonists in cancer patients is stably decreasing, suggesting that drug developers and oncologists are refocusing their interest on alternative immunostimulatory agents. Here, we summarize recent findings on the use of TLR agonists in cancer patients and discuss how the clinical evaluation of FDA-approved and experimental TLR ligands has evolved since the publication of our first Trial Watch dealing with this topic. PMID:25083332

  16. Trial watch

    PubMed Central

    Vacchelli, Erika; Senovilla, Laura; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    It is now clear that the immune system plays a critical role not only during oncogenesis and tumor progression, but also as established neoplastic lesions respond to therapy. Selected cytotoxic chemicals can indeed elicit immunogenic cell death, a functionally peculiar type of apoptosis that stimulates tumor-specific cognate immune responses. Such immunogenic chemotherapeutics include cyclophosphamide, doxorubicin and oxaliplatin (which are approved by FDA for the treatment of various hematological and solid malignancies), mitoxantrone (which is currently employed both as an anticancer agent and against multiple sclerosis) and patupilone (a microtubular poison in clinical development). One year ago, in the second issue of OncoImmunology, we discussed the scientific rationale behind immunogenic chemotherapy and reviewed the status of recent clinical trials investigating the off-label use of cyclophosphamide, doxorubicin, oxaliplatin and mitoxantrone in cancer patients. Here, we summarize the latest developments in this area of clinical research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of immunogenic chemotherapeutics. PMID:23687621

  17. Trial Watch

    PubMed Central

    Vacchelli, Erika; Aranda, Fernando; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct immunostimulatory effects. These three classes of mAbs exert antineoplastic activity via distinct mechanisms, which may or may not involve immune effectors other than the mAbs themselves. In previous issues of OncoImmunology, we provided a brief scientific background to the use of mAbs, all types confounded, in cancer therapy, and discussed the results of recent clinical trials investigating the safety and efficacy of this approach. Here, we focus on mAbs that primarily target malignant cells or their interactions with stromal components, as opposed to mAbs that mediate antineoplastic effects by activating the immune system. In particular, we discuss relevant clinical findings that have been published during the last 13 months as well as clinical trials that have been launched in the same period to investigate the therapeutic profile of hitherto investigational tumor-targeting mAbs. PMID:24605265

  18. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Fridman, Wolf Hervé; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Immunostimulatory monoclonal antibodies (mAbs) exert antineoplastic effects by eliciting a novel or reinstating a pre-existing antitumor immune response. Most often, immunostimulatory mAbs activate T lymphocytes or natural killer (NK) cells by inhibiting immunosuppressive receptors, such as cytotoxic T lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1 (PDCD1, best known as PD-1), or by engaging co-stimulatory receptors, like CD40, tumor necrosis factor receptor superfamily, member 4 (TNFRSF4, best known as OX40) or TNFRSF18 (best known as GITR). The CTLA4-targeting mAb ipilimumab has been approved by the US Food and Drug Administration for use in patients with unresectable or metastatic melanoma in 2011. The therapeutic profile of ipilimumab other CTLA4-blocking mAbs, such as tremelimumab, is currently being assessed in subjects affected by a large panel of solid neoplasms. In the last few years, promising clinical results have also been obtained with nivolumab, a PD-1-targeting mAb formerly known as BMS-936558. Accordingly, the safety and efficacy of nivolumab and other PD-1-blocking molecules are being actively investigated. Finally, various clinical trials are underway to test the therapeutic potential of OX40- and GITR-activating mAbs. Here, we summarize recent findings on the therapeutic profile of immunostimulatory mAbs and discuss clinical trials that have been launched in the last 14 months to assess the therapeutic profile of these immunotherapeutic agents. PMID:24701370

  19. Trial Watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Adoptive cell transfer (ACT) represents a prominent form of immunotherapy against malignant diseases. ACT is conceptually distinct from dendritic cell-based approaches (which de facto constitute cellular vaccines) and allogeneic transplantation (which can be employed for the therapy of hematopoietic tumors) as it involves the isolation of autologous lymphocytes exhibiting antitumor activity, their expansion/activation ex vivo and their reintroduction into the patient. Re-infusion is most often performed in the context of lymphodepleting regimens (to minimize immunosuppression by host cells) and combined with immunostimulatory interventions, such as the administration of Toll-like receptor agonists. Autologous cells that are suitable for ACT protocols can be isolated from tumor-infiltrating lymphocytes or generated by engineering their circulating counterparts for the expression of transgenic tumor-specific T-cell receptors. Importantly, lymphocytes can be genetically modified prior to re-infusion for increasing their persistence in vivo, boosting antitumor responses and minimizing side effects. Moreover, recent data indicate that exhausted antitumor T lymphocytes may be rejuvenated in vitro by exposing them to specific cytokine cocktails, a strategy that might considerably improve the clinical success of ACT. Following up the Trial Watch that we published on this topic in the third issue of OncoImmunology (May 2012), here we summarize the latest developments in ACT-related research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of this form of cellular immunotherapy. PMID:23762803

  20. Trial watch

    PubMed Central

    Senovilla, Laura; Vacchelli, Erika; Garcia, Pauline; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    The foundation of modern vaccinology dates back to the 1790s, when the English physician Edward Jenner uncovered the tremendous medical potential of prophylactic vaccination. Jenner’s work ignited a wave of nationwide vaccination campaigns abating the incidence of multiple life-threatening infectious diseases and culminating with the eradication of natural smallpox virus, which was definitively certified by the WHO in 1980. The possibility of using vaccines against cancer was first proposed at the end of the 19th century by Paul Ehrlich and William Coley. However, it was not until the 1990s that such a hypothesis began to be intensively investigated, following the realization that the immune system is not completely unresponsive to tumors and that neoplastic cells express immunogenic tumor-associated antigens (TAAs). Nowadays, anticancer vaccines are rapidly moving from the bench to the bedside, and a few prophylactic and therapeutic preparations have already been approved by FDA for use in humans. In this setting, one interesting approach is constituted by DNA vaccines, i.e., TAA-encoding circularized DNA constructs, often of bacterial origin, that are delivered to patients as such or by means of specific vectors, including (but not limited to) liposomal preparations, nanoparticles, bacteria and viruses. The administration of DNA vaccines is most often performed via the intramuscular or subcutaneous route and is expected to cause (1) the endogenous synthesis of the TAA by myocytes and/or resident antigen-presenting cells; (2) the presentation of TAA-derived peptides on the cell surface, in association with MHC class I molecules; and (3) the activation of potentially therapeutic tumor-specific immune responses. In this Trial Watch, we will summarize the results of recent clinical trials that have evaluated/are evaluating DNA vaccines as therapeutic interventions against cancer. PMID:23734328

  1. Trial watch

    PubMed Central

    Vacchelli, Erika; Vitale, Ilio; Eggermont, Alexander; Fridman, Wolf Hervé; Fučíková, Jitka; Cremer, Isabelle; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Dendritic cells (DCs) occupy a privileged position at the interface between innate and adaptive immunity, orchestrating a large panel of responses to both physiological and pathological cues. In particular, whereas the presentation of antigens by immature DCs generally results in the development of immunological tolerance, mature DCs are capable of priming robust, and hence therapeutically relevant, adaptive immune responses. In line with this notion, functional defects in the DC compartment have been shown to etiologically contribute to pathological conditions including (but perhaps not limited to) infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. Thus, the possibility of harnessing the elevated immunological potential of DCs for anticancer therapy has attracted considerable interest from both researchers and clinicians over the last decade. Alongside, several methods have been developed not only to isolate DCs from cancer patients, expand them, load them with tumor-associated antigens and hence generate highly immunogenic clinical grade infusion products, but also to directly target DCs in vivo. This intense experimental effort has culminated in 2010 with the approval by the US FDA of a DC-based preparation (sipuleucel-T, Provenge®) for the treatment of asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer. As an update to the latest Trial Watch dealing with this exciting field of research (October 2012), here we summarize recent advances in DC-based anticancer regimens, covering both high-impact studies that have been published during the last 13 mo and clinical trials that have been launched in the same period to assess the antineoplastic potential of this variant of cellular immunotherapy. PMID:24286020

  2. Trial watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    During the past 20 years, dozens—if not hundreds—of monoclonal antibodies have been developed and characterized for their capacity to mediate antineoplastic effects, either as they activate/enhance tumor-specific immune responses, either as they interrupt cancer cell-intrinsic signal transduction cascades, either as they specifically delivery toxins to malignant cells or as they block the tumor-stroma interaction. Such an intense research effort has lead to the approval by FDA of no less than 14 distinct molecules for use in humans affected by hematological or solid malignancies. In the inaugural issue of OncoImmunology, we briefly described the scientific rationale behind the use of monoclonal antibodies in cancer therapy and discussed recent, ongoing clinical studies investigating the safety and efficacy of this approach in patients. Here, we summarize the latest developments in this exciting area of clinical research, focusing on high impact studies that have been published during the last 15 months and clinical trials launched in the same period to investigate the therapeutic profile of promising, yet hitherto investigational, monoclonal antibodies. PMID:23482847

  3. Trial Watch

    PubMed Central

    Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonella minnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of OncoImmunology, we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists. PMID:24083080

  4. Trial Watch

    PubMed Central

    Bloy, Norma; Pol, Jonathan; Manic, Gwenola; Vitale, Ilio; Eggermont, Alexander; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    During the past two decades, it has become increasingly clear that the antineoplastic effects of radiation therapy do not simply reflect the ability of X-, β- and γ-rays to damage transformed cells and directly cause their permanent proliferative arrest or demise, but also involve cancer cell-extrinsic mechanisms. Indeed, among other activities, radiotherapy has been shown to favor the establishment of tumor-specific immune responses that operate systemically, underpinning the so-called ‘out-of-field’ or ‘abscopal’ effect. Thus, ionizing rays appear to elicit immunogenic cell death, a functionally peculiar variant of apoptosis associated with the emission of a particularly immunostimulatory combination of damage-associated molecular patterns. In line with this notion, radiation therapy fosters, and thus exacerbates, the antineoplastic effects of various treatment modalities, including surgery, chemotherapy and various immunotherapeutic agents. Here, we summarize recent advances in the use of ionizing rays as a means to induce or potentiate therapeutically relevant anticancer immune responses. In addition, we present clinical trials initiated during the past 12 months to test the actual benefit of radioimmunotherapy in cancer patients. PMID:25941606

  5. Trial Watch

    PubMed Central

    Pol, Jonathan; Bloy, Norma; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Hervé Fridman, Wolf; Cremer, Isabelle; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    During the past 2 decades, the possibility that preparations capable of eliciting tumor-specific immune responses would mediate robust therapeutic effects in cancer patients has received renovated interest. In this context, several approaches to vaccinate cancer patients against their own malignancies have been conceived, including the administration of DNA constructs coding for one or more tumor-associated antigens (TAAs). Such DNA-based vaccines conceptually differ from other types of gene therapy in that they are not devised to directly kill cancer cells or sensitize them to the cytotoxic activity of a drug, but rather to elicit a tumor-specific immune response. In spite of an intense wave of preclinical development, the introduction of this immunotherapeutic paradigm into the clinical practice is facing difficulties. Indeed, while most DNA-based anticancer vaccines are well tolerated by cancer patients, they often fail to generate therapeutically relevant clinical responses. In this Trial Watch, we discuss the latest advances on the use of DNA-based vaccines in cancer therapy, discussing the literature that has been produced around this topic during the last 13 months as well as clinical studies that have been launched in the same time frame to assess the actual therapeutic potential of this intervention. PMID:24800178

  6. Trial Watch

    PubMed Central

    Semeraro, Michaela; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Lenalidomide is a synthetic derivative of thalidomide currently approved by the US Food and Drug Administration for use in patients affected by multiple myeloma (in combination with dexamethasone) and low or intermediate-1 risk myelodysplastic syndromes that harbor 5q cytogenetic abnormalities. For illustrative purposes, the mechanism of action of lenalidomide can be subdivided into a cancer cell-intrinsic, a stromal, and an immunological component. Indeed, lenalidomide not only exerts direct cell cycle-arresting and pro-apoptotic effects on malignant cells, but also interferes with their physical and functional interaction with the tumor microenvironment and mediates a robust, pleiotropic immunostimulatory activity. In particular, lenalidomide has been shown to stimulate the cytotoxic functions of T lymphocytes and natural killer cells, to limit the immunosuppressive impact of regulatory T cells, and to modulate the secretion of a wide range of cytokines, including tumor necrosis factor α, interferon γ as well as interleukin (IL)-6, IL-10, and IL-12. Throughout the last decade, the antineoplastic and immunostimulatory potential of lenalidomide has been investigated in patients affected by a wide variety of hematological and solid malignancies. Here, we discuss the results of these studies and review the status of clinical trials currently assessing the safety and efficacy of this potent immunomodulatory drug in oncological indications. PMID:24482747

  7. Trial Watch

    PubMed Central

    Aranda, Fernando; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-01-01

    Throughout the past 3 decades, along with the recognition that the immune system not only influences oncogenesis and tumor progression, but also determines how established neoplastic lesions respond therapy, renovated enthusiasm has gathered around the possibility of using vaccines as anticancer agents. Such an enthusiasm quickly tempered when it became clear that anticancer vaccines would have to be devised as therapeutic, rather than prophylactic, measures, and that malignant cells often fail to elicit (or actively suppress) innate and adaptive immune responses. Nonetheless, accumulating evidence indicates that a variety of anticancer vaccines, including cell-based, DNA-based, and purified component-based preparations, are capable of circumventing the poorly immunogenic and highly immunosuppressive nature of most tumors and elicit (at least under some circumstances) therapeutically relevant immune responses. Great efforts are currently being devoted to the identification of strategies that may provide anticancer vaccines with the capacity of breaking immunological tolerance and eliciting tumor-associated antigen-specific immunity in a majority of patients. In this sense, promising results have been obtained by combining anticancer vaccines with a relatively varied panels of adjuvants, including multiple immunostimulatory cytokines, Toll-like receptor agonists as well as inhibitors of immune checkpoints. One year ago, in the December issue of OncoImmunology, we discussed the biological mechanisms that underlie the antineoplastic effects of peptide-based vaccines and presented an abundant literature demonstrating the prominent clinical potential of such an approach. Here, we review the latest developments in this exciting area of research, focusing on high-profile studies that have been published during the last 13 mo and clinical trials launched in the same period to evaluate purified peptides or full-length proteins as therapeutic anticancer agents. PMID:24498550

  8. How Do Clinical Trials Work?

    MedlinePlus

    ... Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites How Do Clinical Trials Work? If you take part in a clinical trial, ...

  9. Clinical Trials - Multiple Languages

    MedlinePlus

    ... Tiếng Việt) Arabic (العربية) Expand Section Clinical Trials - English Clinical Trials - العربية (Arabic) PDF American Cancer Society ... Traditional (Cantonese dialect) (繁體中文) Expand Section Clinical Trials - English Clinical Trials - 繁體中文 (Chinese, Traditional (Cantonese dialect)) PDF ...

  10. Clinical trials of homoeopathy.

    PubMed Central

    Kleijnen, J; Knipschild, P; ter Riet, G

    1991-01-01

    OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

  11. Managing clinical trials

    PubMed Central

    2010-01-01

    Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation. PMID:20626885

  12. Remune trial will stop; new trials planned.

    PubMed

    James, J S

    1999-05-21

    A clinical trial using remune, the anti-HIV vaccine developed by the late Dr. Jonas Salk, has been ended. The study is a clinical-endpoint trial which looks for statistically significant differences in AIDS sickness or death between patients who add remune to their treatment regimens versus those who use a placebo. Agouron Pharmaceuticals and the Immune Response Corporation who were conducting the trial announced their decision to stop it after an analysis by the Data Safety Monitoring Board. No differences in clinical endpoints were found and it was projected that continuing the trial would likely not find any. The companies are now planning two new Phase III trials using viral load testing rather than clinical endpoints as study criteria.

  13. Teaching Drama Via Trials.

    ERIC Educational Resources Information Center

    Mansour, Wisam

    1998-01-01

    Suggests using a court trial as an activity for teaching drama to English-as-a-foreign-language (EFL) students. Describes use of a court trial for teaching Macbeth to EFL students in Jordan. (Author/VWL)

  14. Research Areas - Clinical Trials

    Cancer.gov

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  15. ClinicalTrials.gov

    MedlinePlus

    ... Content ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ... This Site ClinicalTrials.gov Background About the Results Database History, Policies, and Laws Media/Press Resources Linking ...

  16. Salem Witch Trials.

    ERIC Educational Resources Information Center

    Ray, Benjamin

    2003-01-01

    Presents a lesson plan that focuses on the Salem (Massachusetts) witchcraft trials. Explains that the first section of the lesson has students learn about the trials as described in the court records. The second section asks students to interpret various images of the trials. (CMK)

  17. Salem Witch Trials.

    ERIC Educational Resources Information Center

    Ray, Benjamin

    2003-01-01

    Presents a lesson plan that focuses on the Salem (Massachusetts) witchcraft trials. Explains that the first section of the lesson has students learn about the trials as described in the court records. The second section asks students to interpret various images of the trials. (CMK)

  18. Cholesterol trials and mortality.

    PubMed

    Warren, John B; Dimmitt, Simon B; Stampfer, Hans G

    2016-07-01

    An overview of clinical trials can reveal a class effect on mortality that is not apparent from individual trials. Most large trials of lipid pharmacotherapy are not powered to detect differences in mortality and instead assess efficacy with composite cardiovascular endpoints. We illustrate the importance of all-cause mortality data by comparing survival in three different sets of the larger controlled lipid trials that underpin meta-analyses. These trials are for fibrates and statins. Fibrate treatment in five of the six main trials was associated with a decrease in survival, one fibrate trial showed a non-significant reduction in mortality that can be explained by a different target population. In secondary prevention, statin treatment increased survival in all five of the main trials, absolute mean increase ranged from 0.43% to 3.33%, the median change was 1.75%, which occurred in the largest trial. In primary prevention, statin treatment increased survival in six of the seven main trials, absolute mean change in survival ranged from -0.09% to 0.89%, median 0.49%. Composite safety endpoints are rare in these trials. The failure to address composite safety endpoints in most lipid trials precludes a balanced summary of risk-benefit when a composite has been used for efficacy. Class effects on survival provide informative summaries of the risk-benefit of lipid pharmacotherapy. We consider that the presentation of key mortality/survival data adds to existing meta-analyses to aid personal treatment decisions.

  19. [CLINICAL TRIAL DESIGN].

    PubMed

    Morita, Satoshi

    2016-01-01

    Clinical trials/research are conducted to examine the clinical questions of practicing physicians. It is important to design trials appropriately in advance, taking their feasibility into account. A randomized, controlled trial is the ultimate design for treatment comparisons at the final confirmatory stage. However, randomized trials do not necessarily provide all answers to clinical questions. This article summarizes fundamental points of clinical trial design and the important role of randomization and contrasts superiority and noninferiority trials. In addition, it focuses on propensity score matching, a useful method to compare two treatment arms, especially in the context where randomization is infeasible. The propensity score-matching method is increasingly used in surgical clinical research.

  20. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports.

  1. Beyond trial types.

    PubMed

    Dyrholm, Mads; Vangkilde, Signe; Bundesen, Claus

    2015-05-01

    Conventional wisdom on psychological experiments has held that when one or more independent variables are manipulated it is essential that all other conditions are kept constant such that confounding factors can be assumed negligible (Woodworth, 1938). In practice, the latter assumption is often questionable because it is generally difficult to guarantee that all other conditions are constant between any two trials. Therefore, the most common way to check for confounding violations of this assumption is to split the experimental conditions in terms of "trial types" to simulate a reduction of unintended trial-by-trial variation. Here, we pose a method which is more general than the use of trial types: use of mathematical models treating measures of potentially confounding factors and manipulated variables as equals on the single-trial level. We show how the method can be applied with models that subsume under the generalized linear item response theory (GLIRT), which is the case for most of the well-known psychometric models (Mellenbergh, 1994). As an example, we provide a new analysis of a single-letter recognition experiment using a nested likelihood ratio test that treats manipulated and measured variables equally (i.e., in exactly the same way) on the single-trial level. The test detects a confounding interaction with time-on-task as a single-trial measure and yields a substantially better estimate of the effect size of the main manipulation compared with an analysis made in terms of trial types.

  2. Clinical trial structures

    PubMed Central

    Evans, Scott R.

    2011-01-01

    Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. The selection of a clinical trial design structure requires logic and creativity. Common structural designs are discussed. PMID:21423788

  3. Strategy trials: the answer?

    PubMed

    James, J S

    1999-02-19

    Although a significant amount of promotional information on drugs was presented at the 6th Conference on Retroviruses and Opportunistic Infections, very little of it was related to practical treatment strategy. Doctors and patients have many options but little guidance on selecting which combination of drugs will be most beneficial in long-term use. There is a growing call for "strategy trials" designed to answer those questions. Pharmaceutical companies traditionally have not done strategy trials; their testing is designed to promote their own products. Managing patients in strategy trials is also difficult because they have to fail a treatment before another combination of drugs is used. In addition, collecting valid data from a stragety trial takes longer than collecting data from a starting regimen trial.

  4. Clinical trial registration in fertility trials - a case for improvement?

    PubMed

    Farquhar, Cynthia M; Showell, Marian G; Showell, Emily A E; Beetham, Penny; Baak, Nora; Mourad, Selma; Jordan, Vanessa M B

    2017-09-01

    What is the prevalence and source of prospectively and retrospectively registered and unregistered trials in fertility treatments? Trial registration is low and does not appear to be changing over the 5 years studied. Trial registration is associated with lower risk of bias than in unregistered trials. The Cochrane Gynaecology and Fertility Group's specialised register was searched on 5 November 2015 for randomised controlled trials (RCTs) published from January 2010 to December 2014. Eligible trials included randomised women or men for fertility treatments, were published in full text, and written in English. Two reviewers independently assessed trial registration status for each trial, by searching the publication, trial registries, and by contacting the original authors. Of 693 eligible RCTS, only 44% were registered trials. Of 309 registered trials, 21.7% were prospectively registered, 15.8% were registered within 6 months of first patient enrolment and 62.5% were retrospectively registered trials. Prospective trial registration by country varied from 0% to 100%. The highest frequency of prospective trial registration amongst the top 10 publishing countries was 31% in the Netherlands. Only English language trials were included in this review. Prospective trial registration is still low. Journals, funders and ethics committees could have a greater role to increase trial registration. University of Auckland. No competing interests.

  5. [Globalization of clinical trials].

    PubMed

    Akaza, Hideyuki; Fukuoka, Masahiro; Ohtsu, Atsushi; Usami, Michiyuki; Ikeda, Tadashi; Aiba, Keisuke; Isonishi, Seiji; Ohashi, Yasuo; Saijo, Nagahiro; Sone, Saburo; Tsukagoshi, Shigeru; Tsuruo, Takashi; Kato, Masuhiro; Mikami, Osamu; Dong, Rui-Ping; von Euler, Mikael; Blackledge, George; Stribling, Don

    2003-04-01

    Based on reviews of the Japanese clinical trial situation in lung cancer, gastric cancer, prostate cancer and breast cancer, it was clear that much progress has been made in short time. There are considerable differences between Japan and the West and also differences between clinical areas in Japan. For regulatory purposes bridging studies have become increasingly important. Use of identical protocols are required for effective bridging. Participations in global phase III trials is the best way of achieving registration in Japan. For successful global trials in Japan it is important to include Japanese investigators in the preparation of the protocol and to recognise the challenges facing such a project. Clinical practice in diagnosis and treatment have many differences, thus it is recommended to have clear and detailed information in the protocol. Hard end points like survival are important since they are not biased by cultural differences. There are clear difficulties with HE or QOL outcomes. The emergence of focus on evidence based medicine is also happening in Japan and will help to harmonize documentation across the world. For large adjuvant or prevention cancer global trials are essential. To facilitate global studies further development of infrastructure is necessary in Japan. Use of electronic data capture web based communication etc. will help overcome communication difficulties. Other improvements that will make Japanese participation in global trials easier and better include establishment of clinical trial centre at each hospital, introduction of trial coordinators or study nurses and an improved collaboration with company staff. A critical issue that also need addressing is agreement of centre target recruitment. We need to introduce a new flexible system in Japan if participation in global trial is to be optimised. If we can address these issues Japanese investigators and collaborative groups should be able to initiate and lead global trials in the

  6. [Evaluation of clinical trials].

    PubMed

    Ural, Dilek

    2010-03-01

    Women are under-represented in landmark clinical trials that form the basis of evidence based management of cardiovascular diseases. Differences among male and female patients emerged in effectiveness and safety of therapeutics in some diseases. Especially in dyslipidemia, ischemic heart diseases and heart failure, trials in which women are better represented and guidelines that evaluate findings in women more detailed are needed. This article evaluates differences among men and women in some landmark trials that are used among main references in management guidelines.

  7. Polyp Prevention Trial

    Cancer.gov

    The primary objective of the Polyp Prevention Trial (PPT) is to determine whether a low fat, high fiber, high vegetable and fruit eating plan will decrease the recurrence of adenomatous polyps of the large bowel.

  8. Anchor Trial Launch

    Cancer.gov

    NCI has launched a multicenter phase III clinical trial called the ANCHOR Study -- Anal Cancer HSIL (High-grade Squamous Intraepithelial Lesion) Outcomes Research Study -- to determine if treatment of HSIL in HIV-infected individuals can prevent anal canc

  9. TrialNet

    MedlinePlus

    ... If you have T1D in your family, your participation can be the difference. A simple blood test ... through a TrialNet screening and explains how their participation can make a difference in type 1 diabetes ...

  10. Hepatitis C: Clinical Trials

    MedlinePlus

    ... Financial Report (AFR) Budget Submission Recovery Act Resources Business Congressional Affairs Jobs Benefits Booklet Data & Statistics National ... Participation in any clinical trial is voluntary and choosing not to participate will not affect your VA ...

  11. Informed Consent (Clinical Trials)

    MedlinePlus

    ... Credit: National Cancer Institute Informed consent is a process through which you learn details about the trial before deciding whether to take part. This includes learning about the trial’s purpose and possible risks and ...

  12. Monotherapy trials: presurgical studies.

    PubMed

    Pledger, G

    2001-05-01

    Presurgical evaluation of patients with refractory partial seizures provides a unique opportunity to perform a placebo-controlled, monotherapy trial. Some patients undergoing presurgical evaluations must have all of their antiepileptic drugs (AEDs) tapered in order to induce seizures and therefore such patients are possible candidates for a placebo-controlled monotherapy trial. Often, EEG monitoring is continued throughout the trial period, thus patients either receiving placebo or whose seizures do not completely respond to the active drug are still evaluated to determine whether or not surgery is feasible, supporting the validity of a trial in this setting. In addition, all patients are, in general, eligible to receive the study drug after the blinded period of the trial, and can therefore be assured of the possible therapeutic benefits of the study. Presurgical inpatients studies have been carried out using felbamate, gabapentin and oxcarbazepine. All patients randomised in these trials were refractory to previous treatment and the studies themselves were short-term and placebo-controlled. These presurgical studies are designed to elucidate AED activity and show statistically significant differences between active and control treatments during short-term therapy, and are therefore of use in fulfilling regulatory requirements. However, these measures of efficacy are distinctly different from those determined during chronic treatment and are therefore not necessarily predictive of clinical usefulness.

  13. Clinical Trials Corner: September 2017.

    PubMed

    Rodrigues, Filipe B; Wild, Edward J

    2017-01-01

    Clinical Trials Corner of Journal of Huntington's Disease will regularly review ongoing and recently completed clinical trials in Huntington's disease. In this inaugural issue, we list all currently registered and ongoing clinical trials, expand on LEGATO-HD and IONIS-HTTRx, and cover two recently finished trials: Amaryllis and Pride-HD.

  14. Challenges of cluster randomized trials.

    PubMed

    Campbell, Michael J

    2014-05-01

    Cluster randomized trials are trials that randomize clusters of people, rather than individuals. They are becoming increasingly common. A number of innovations have been developed recently, particularly in the calculation of the required size of a cluster trial, the handling of missing data, designs to minimize recruitment bias, the ethics of cluster randomized trials and the stepped wedge design. This article will highlight and illustrate these developments. It will also discuss issues with regards to the reporting of cluster randomized trials.

  15. Ethics and clinical trials.

    PubMed

    Chassany, O; Duracinský, M

    1999-01-01

    The current reference guideline about ethics in clinical trials is the Declaration of Helsinki of human rights in medical research. Three major principles are emphasised: respect of the patient to accept or not to participate in a trial, the constraints and the presumed risks must be acceptable for patients included in a study, and vulnerable subjects should not participate in studies. The investigator is responsible for obtaining a free and well-informed consent from patients before their inclusion in a study. Where possible, a new drug should always first be compared to placebo in order to prove its superiority. Else, a small-sized trial comparing a new drug versus a reference treatment can lead to an erroneous conclusion of absence of difference. Moreover, good results or improvement are obtained in at least 30% of cases with placebo, whatever the disease. The use of placebo is unethical in life-threatening diseases and when an effective proved drug exists. The use of placebo is ethical in severe diseases with no efficient drug, in some severe diseases even when an active reference treatment is available, and in all moderate and functional diseases. In order to detect flawed studies, most journals now ask for any manuscript submitted and reporting results of a randomised clinical trial to join a checklist in order to verify the quality of the trial. Finally, it remains the responsibility of the doctor to decide whether or not a protocol is ethical, to participate or not and to include patients or not.

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-05-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, 101M, AAV-AADC, AGN-201904-Z; Agomelatine, AN-0128, AN-2690, Arginine butyrate, Asenapine maleate; Belinostat, Bortezomib, BQ-123, BQ-788; Bucindolol hydrochloride; Certolizumab pegol; Dasatinib, Denosumab, Desvenlafaxine succinate; Ecogramostim, Esomeprazole magnesium; Homoharringtonine; huN901-DM1, Hyaluronic acid; Incyclinide; L-Arginine hydrochloride; Mepolizumab; Nematode anticoagulant protein c2, Nilotinib; Oblimersen sodium; R-115866, Raltegravir potassium, Retapamulin, Romidepsin, Rusalatide acetate; Sarcosine, SCIO-469, Soblidotin, Sorivudine; Tilarginine hydrochloride, Tipifarnib; Uracil; Vildagliptin. (c) 2007 Prous Science. All rights reserved.

  17. Volunteering for clinical trials.

    PubMed

    Mirken, B

    1999-04-01

    HIV/AIDS researchers are finding it increasingly difficult to recruit volunteers for their studies, and are working on designing studies that are more broadly applicable and palatable to the volunteers. Studies offer both opportunities and risks for people who volunteer. This overview describes the basics of trial design and practice, with the purposes of each trial phase clearly described. Participation requires informed consent, and before entering a study patients should ask, among other things, what side effects they can expect, and who will manage their treatment.

  18. Cereal Rye Performance Trial

    USDA-ARS?s Scientific Manuscript database

    Research performance trials were conducted with an experimental cereal rye (Chason) against check varieties Elbon, Maton, Oklon and wheat under low N conditions (40lbs/ac). Earlier evaluations had identified Chason as a superior and productive cereal rye when evaluated under severe drought or high ...

  19. Clinical Trials: CSDRG Overview

    ERIC Educational Resources Information Center

    Logemann, Jeri A.

    2004-01-01

    Recent importance placed upon efficacy research has spawned the development of the Communication Sciences and Disorders Clinical Trials Research Group (CSDRG). This group, funded by the National Institutes of Health (NIH), was organized by the American Speech Language and Hearing Association to address the need for more treatment efficacy research…

  20. Statistically Valid Planting Trials

    Treesearch

    C. B. Briscoe

    1961-01-01

    More than 100 million tree seedlings are planted each year in Latin America, and at least ten time'that many should be planted Rational control and development of a program of such magnitude require establishing and interpreting carefully planned trial plantings which will yield statistically valid answers to real and important questions. Unfortunately, many...

  1. Adaptive clinical trial design.

    PubMed

    Chow, Shein-Chung

    2014-01-01

    In recent years, the use of adaptive design methods in clinical trials based on accumulated data at interim has received much attention because of its flexibility and efficiency in pharmaceutical/clinical development. In practice, adaptive design may provide the investigators a second chance to modify or redesign the trial while the study is still ongoing. However, it is a concern that a shift in target patient population may occur after significant adaptations are made. In addition, the overall type I error rate may not be preserved. Moreover, the results may not be reliable and hence are difficult to interpret. As indicated by the US Food and Drug Administration draft guidance on adaptive design clinical trials, the adaptive design has to be a prospectively planned opportunity and should be based on information collected within the study, with or without formal statistical hypothesis testing. This article reviews the relative advantages, limitations, and feasibility of commonly considered adaptive designs in clinical trials. Statistical concerns when implementing adaptive designs are also discussed.

  2. Types of Treatment: Clinical Trials

    MedlinePlus

    ... Initiative Grant Finder Therapy Acceleration Program Academic Concierge Biotechnology Accelerator Clinical Trials Division Special Projects Beat AML ... Initiative Grant Finder Therapy Acceleration Program Academic Concierge Biotechnology Accelerator Clinical Trials Division Special Projects Beat AML ...

  3. Clinical Trials in Vision Research

    MedlinePlus

    ... the right choice for you. What are the costs of a clinical trial? All medical care provided ... Clinical trials conducted at other locations may involve costs related to standard medical care. These may or ...

  4. The Trial of Katherine Harrison.

    ERIC Educational Resources Information Center

    Woodward, Walter W.

    2003-01-01

    Presents a lesson plan in which the teacher and students participate in a mock trial of Katherine Harrison, who was accused of witchcraft in the seventeenth century. Provides background information about the trial, as well as primary sources of the testimonies given by witnesses during the trial. (CMK)

  5. Improving transparency of clinical trials.

    PubMed

    Dal-Ré, Rafael

    2015-06-01

    Recent data reveal that subtle selective publication affects critical aspects of trial reporting, in some cases altering the interpretation of results. Timely prospective registration could help deter selective reporting and clinical trial stakeholders from government authorities to journal editors should work together to foster prospective registration of trials.

  6. Bibliography of Mock Trial Materials.

    ERIC Educational Resources Information Center

    National Inst. for Citizen Education in the Law, Washington, DC.

    This catalog lists general articles on mock trials, information for arranging mock trial competitions, mock trial problem sets, and video tapes. The problem sets contain introductory material, applicable law, statements of facts, witness statements, and documents. The cases include issues in family, consumer, criminal, and immigration law. Several…

  7. [PRIMER FOR SURGICAL CLINICAL TRIALS].

    PubMed

    Sakamaki, Kentaro; Yamanaka, Takeharu

    2016-01-01

    Clinical trials are conducted based on the development of surgical technology and are designed to answer specific research questions. In planning clinical trials population, intervention, comparison, and outcome are important elements. Sample size calculation is also central to the design of clinical trials, especially randomized, controlled ones. This article outlines study phases, four important elements of design, and sample size calculation.

  8. Street Law Mock Trial Manual.

    ERIC Educational Resources Information Center

    McGuire, Patricia, Ed.; O'Brien, Edward L.; Arbetman, Lee; Mills, Vivian H.; Pannell, Andrew

    Designed to facilitate the expanded use of mock trials, this manual is divided into two principle sections--a teacher's guide and a student's guide. The teacher's guide contains specific advice to teachers on all aspects of preparing for a mock trial and seven specific lesson plans for a 2- to 3-week mock trial unit. Each lesson contains…

  9. The Trial of Katherine Harrison.

    ERIC Educational Resources Information Center

    Woodward, Walter W.

    2003-01-01

    Presents a lesson plan in which the teacher and students participate in a mock trial of Katherine Harrison, who was accused of witchcraft in the seventeenth century. Provides background information about the trial, as well as primary sources of the testimonies given by witnesses during the trial. (CMK)

  10. Clinical Trials Information for Patients and Caregivers

    MedlinePlus

    ... Trials Phases of Clinical Trials Randomization Use of Placebos Research Team Members Paying for Clinical Trials Insurance ... types of clinical trials. Also, explains phases, randomization, placebo, and members of the research team. Paying for ...

  11. Funding oncology clinical trials: are cooperative group trials sustainable?

    PubMed

    Seow, Hsien-Yeang; Whelan, Patrick; Levine, Mark N; Cowan, Kathryn; Lysakowski, Barbara; Kowaleski, Brenda; Snider, Anne; Xu, Rebecca Y; Arnold, Andrew

    2012-05-01

    Many oncology clinical trials departments (CTDs) are in serious fiscal deficit and their sustainability is in jeopardy. This study investigates whether the payment models used to fund industry versus cooperative group trials contribute to the fiscal deficit of a CTD. We examined the lifetime costs of all cooperative group and industry trials activated in the CTD of a cancer center between 2007 and 2011. A trial's lifetime is defined as being from the date the first patient was accrued until the last patient's actual or projected final follow-up visit. For each trial, we calculated the lifetime monthly net income, which was defined as monthly revenue minus monthly costs. Data sources included study protocols, trial budgets, and accrual data. Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of lifetime net income for cooperative group trials has a positive peak during patient accrual followed by a negative trough during follow-up. In contrast, the pattern for industry trials resembled an "l" shape. The patterns reflect the differing payment models: upfront lump-sum payments (cooperative group) versus milestone payments (industry). The negative trough in the lifetime net income of a cooperative group trial occurs because follow-up costs are typically not funded or are underfunded. CTDs accrue more patients in new trials to offset that deficit. The CTD uses revenue from accrual to existing trials to cross-subsidize past trials in follow-up. As the number of patients on follow-up increases, the fiscal deficit grows larger each year, perpetuating the cycle.

  12. A randomised controlled trial of nurse-managed trial conclusion following early phase cancer trial participation.

    PubMed

    Cox, K; Wilson, E; Arthur, A; Elkan, R; Armstrong, S

    2005-07-11

    The effect of a nurse-managed intervention, for early phase cancer trial participants at trial conclusion, on psychosocial outcomes was evaluated at two cancer centres in the Midlands, England using a randomised controlled trial. It involved 117 patients who were participating in an early phase cancer clinical trial. It was a nurse-managed trial exit, which included a trial exit interview, trial feedback information leaflet and telephone follow-up compared with standard care at trial conclusion. Psychological distress at 1 week and 4-6 weeks post-trial conclusion, patient's knowledge and understanding and patient's satisfaction were assessed. The results showed there was no significant difference between the two groups regarding scores for anxiety and depression at time one and time two. There is some suggestion that the intervention reduced anxiety from trial conclusion to follow-up (P=0.27). Patients in both groups felt they had contributed to cancer research through trial participation. However, intervention patients were more likely to feel that they knew how the trial was going (P<0.001), knew how other people in the trial were doing (P=0.001), had all the feedback they needed about the trial they took part in (P<0.01) and knew how they would be followed up (P=0.02). Patient satisfaction with the intervention was high (median score=4.5 where 5 is greatest satisfaction). In conclusion, nurse-managed trial conclusion led to positive outcomes for patients who had recently completed a clinical trial.

  13. SMi's Conducting Clinical Trials in Europe.

    PubMed

    Jago, Charlotte

    2009-12-01

    The Conducting Clinical Trials in Europe meeting, held in London, included topics covering new developments in the field of clinical trials and recommendations on how to best conduct a trial. This conference report highlights selected presentations on the state of affairs of trials in Europe, conducting trials in emerging markets, strategies for improving trials, trial design options, peri-approval and pediatric trials, and the role of key players, such as physicians. Company perspectives from Pfizer Inc and Nycomed are also included.

  14. CD19-CAR Trials

    PubMed Central

    Ramos, Carlos A.; Savoldo, Barbara; Dotti, Gianpietro

    2014-01-01

    CD19 is a B-lineage specific transmembrane glycoprotein, the expression of which is maintained on more than 95% B-cell malignancies. This strict lineage restriction makes CD19 an ideal target for immune therapies using chimeric antigen receptors (CARs). Here we review published phase I trials of T cells expressing CARs targeting CD19 and describe briefly the biological questions that they addressed. All patients treated in these trials had relapsed B-cell malignancies, which in many cases were chemorefractory. Nonetheless, major responses have been observed, especially in patients with CLL and ALL. Many of these responses were accompanied by a systemic inflammatory reaction syndrome that could be life-threatening but was almost always reversible with adequate medical management. Given their remarkable activity, CD19-CAR T cells are likely to be quickly incorporated into the management of B-cell neoplasms and have become the paradigm for similar strategies targeting other cancers. PMID:24667955

  15. Innovative Clinical Trial Designs

    PubMed Central

    Lavori, Philip W.

    2015-01-01

    Whereas the 20th-century health care system sometimes seemed to be inhospitable to and unmoved by experimental research, its inefficiency and unaffordability have led to reforms that foreshadow a new health care system. We point out certain opportunities and transformational needs for innovations in study design offered by the 21st-century health care system, and describe some innovative clinical trial designs and novel design methods to address these needs and challenges. PMID:26140056

  16. The CYTONOX trial.

    PubMed

    Gade, Christina; Mikus, Gerd; Christensen, Hanne Rolighed; Dalhoff, Kim Peder; Holm, Jens-Christian; Holst, Helle

    2016-05-01

    In Denmark, it is estimated that 3-5% of children are obese. Obesity is associated with pathophysiological alterations that may lead to alterations in the pharmacokinetics of drugs. In adults, obesity was found to influence important drug-metabolising enzyme pathways. The impact of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults. An altered drug metabolism may contribute significantly to therapeutic failure or toxicity. The aim of this trial is to investigate the in vivo activity of CYP3A4, CYP2E1 and CYP1A2 substrates in obese versus non-obese children. The CYTONOX trial is an open-label explorative pharmacokinetic trial. We intend to include 50 obese and 50 non-obese children. The primary end points are: in vivo clearance of CYP3A4, CYP2E1 and CYP1A2 substrates, which will be defined by using well-tested probes; midazolam, chlorzoxazone and caffeine. Each of the probes will be administered as a single dose. Subsequently, blood and urine samples will be collected at pre-specified times. The aim of the CYTONOX trial is to investigate the in vivo activity of CYP3A4, CYP2E1 and CYP1A2 in obese and non-obese children. The results are expected to be used in the future as a basis for drug dosing recommendations in obese children. The study was funded by the Danish Regions' "Medicinpuljen". The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. EudraCT: 2014-004554-34.

  17. Evidence and Clinical Trials.

    NASA Astrophysics Data System (ADS)

    Goodman, Steven N.

    1989-11-01

    This dissertation explores the use of a mathematical measure of statistical evidence, the log likelihood ratio, in clinical trials. The methods and thinking behind the use of an evidential measure are contrasted with traditional methods of analyzing data, which depend primarily on a p-value as an estimate of the statistical strength of an observed data pattern. It is contended that neither the behavioral dictates of Neyman-Pearson hypothesis testing methods, nor the coherency dictates of Bayesian methods are realistic models on which to base inference. The use of the likelihood alone is applied to four aspects of trial design or conduct: the calculation of sample size, the monitoring of data, testing for the equivalence of two treatments, and meta-analysis--the combining of results from different trials. Finally, a more general model of statistical inference, using belief functions, is used to see if it is possible to separate the assessment of evidence from our background knowledge. It is shown that traditional and Bayesian methods can be modeled as two ends of a continuum of structured background knowledge, methods which summarize evidence at the point of maximum likelihood assuming no structure, and Bayesian methods assuming complete knowledge. Both schools are seen to be missing a concept of ignorance- -uncommitted belief. This concept provides the key to understanding the problem of sampling to a foregone conclusion and the role of frequency properties in statistical inference. The conclusion is that statistical evidence cannot be defined independently of background knowledge, and that frequency properties of an estimator are an indirect measure of uncommitted belief. Several likelihood summaries need to be used in clinical trials, with the quantitative disparity between summaries being an indirect measure of our ignorance. This conclusion is linked with parallel ideas in the philosophy of science and cognitive psychology.

  18. NATO SOCMET trials

    NASA Astrophysics Data System (ADS)

    Jenden, C. M.

    1993-11-01

    During 1993, Canada, France, Germany and the United Kingdom will be participating in the Smoke and Obscurants Countermeasures Materials Evaluation Tests (SOCMET). The tests will be carried out under the auspices of the NATO Army Armaments Group, AC/225, Panel VI, Sub-Panel 7 whose interests include multispectral smoke screening systems. The tests will comprise two sets of trials; one under cold climate conditions in Quebec, Canada, during February/March 1993 and the other in temperate conditions in Bourges, France during September 1993. This paper provides an insight into the management and aims of SOCMET. The evaluations will be seeking to identify candidate materials which create effective obscurant screens in the visible, infrared and millimetric bands of the electromagnetic spectrum. These materials will be disseminated through a range area dispersal. A key element of the trials will be the evaluation of field test instrumentation which may eventually lead to the development of standardized evaluation techniques. Following the trials, a scientific workshop will be held to review the results. A final report will be presented to NATO which will form the basis of future collaborative developments on multispectral screening systems leading towards standard NATO documentation on smoke and obscurant systems.

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. Copyright 2005 Prous Science. All rights reserved.

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: 4'-Thio-ara-C, 5-methyltetrahydrofolate; ABT-089, AD-237, AF-37702, alvocidib hydrochloride, apricitabine, armodafinil, atrasentan, AVE-5883, avian influenza vaccine, azimilide hydrochloride; Banoxantrone, BIBF-1120; CD34+ cells, certolizumab pegol, CHIR-258, cilansetron, CoFactor, CX-3543, cystemustine; D-003, dexloxiglumide, DMXB-anabaseine; Ecogramostim, elcometrine, elcometrine/ethinylestradiol, etravirine; Fenretinide, fingolimod hydrochloride, fospropofol disodium; Gaboxadol, gestodene, glutamine; Human insulin, hyaluronic acid; Incyclinide, indacaterol, ispronicline, istradefylline; Labradimil, lamifiban, lapatinib, L-arginine hydrochloride, liposomal cisplatin, liposome encapsulated paclitaxel, LY-517717; Manidipine hydrochloride/delapril hydrochloride, maraviroc, MBP(82-98), MD-0727, MDX-214, melanotan I, MMR vaccine; Nacystelyn, nalfurafine hydrochloride, nibentan, nilotinib, NK-105; OBI-1, oblimersen sodium, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, oregovomab; Pexelizumab, PG-116800, PG-CPT, PHA-794428, prasugrel; RC-3095, rDNA insulin, RFB4(dsFv)-PE38, rhEndostatin, rhenium Re-186 etidronate, rhGM-CSF, roflumilast, romidepsin; Sarcosine, SGLU1, SGN-40, succinobucol; TAU, teduglutide, telatinib, tesofensine, tipifarnib, tirapazamine, TKA-731, tolvaptan, trabectedin; Vaccimel, vatalanib succinate, velafermin, vildagliptin, vinflunine; XP-19986; YM-155.

  1. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  2. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  3. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  5. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-10-01

    Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar

  6. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  7. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5-Methyltetrahydrofolate, 9-aminocamptothecin; AdPEDF.11, AE-37, albumin interferon alfa, alicaforsen sodium, alvocidib hydrochloride, AMG-706, arginine butyrate, avanafil, axitinib, azimilide hydrochloride; BAY-579352, belagenpumatucel-L, beta-lapachone, BHT-3009, BIBW-2992, bremelanotide, BX-471; Casopitant mesylate, cediranib, certolizumab pegol, CH-1504, ChimeriVax-West Nile, clofazimine, CpG-7909, curcumin, Cypher; Dapoxetine hydrochloride, darusentan, diflomotecan, D-methionine, dnaJP1, D-serine, DTPw-HB Hib-MenAC, DTPw-HepB-Hib; E-7010, ecogramostim, edodekin alfa, EGFRvlll peptide vaccine, elcometrine, elcometrine/ethinylestradiol, elsilimomab, enrasentan, ertumaxomab, etalocib sodium, exisulind; Fenretinide, fesoterodine, fingolimod hydrochloride, fontolizumab; Gefitinib, gemtuzumab ozogamicin, ghrelin (human), GV-1001; HTU-PA, human papillomavirus vaccine; Indacaterol, indiplon, interleukin-21, intranasal insulin, irinotecan hydrochloride/floxuridine, ISIS-301012, ispinesib mesylate, ixabepilone; K562/GM-CSF; Lapatinib, L-BLP-25, linezolid, liposome encapsulated paclitaxel, LY-2124275; MC-1, MC-1/lisinopril, MDX-066, melanoma vaccine, MMR-V, multivalent (ACYW) meningitis vaccine; Nilotinib, nobori, nociceptin; Oblimersen sodium, orbofiban acetate, ospemifene; Paliperidone, panitumumab, PEG-filgrastim, PEGylated interferon alfacon-1, perflubutane, pertuzumab, phenserine tartrate, phVEGF-A165, pleconaril, prasugrel, prednisolone sodium metasulfobenzoate; R-411, recombinant malaria vaccine, rhGM-CSF, roflumilast, romidepsin, ruboxistaurin mesilate hydrate; Sirolimus-eluting stent, SR-4554, St. John

  8. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide

  9. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  10. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    2008-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir

  11. The trials of Galileo

    NASA Astrophysics Data System (ADS)

    Gingerich, Owen

    2009-12-01

    There are so many books about Galileo, author Dan Hofstadter remarks, so why another? Given that 2009 marks the 400th anniversary of the first astronomical use of the telescope, where Galileo's role was paramount, the answer may seem obvious. But that is not where the strength of Hofstadter's book lies. In The Earth Moves: Galileo and the Roman Inquisition, he instead advances the clock to 1633, towards the end of the Italian scientist's career and the year of the infamous trial that resulted after Galileo's Dialogue on the Two Great World Systems was published in 1632.

  12. Likelihood and clinical trials.

    PubMed

    Hill, G; Forbes, W; Kozak, J; MacNeill, I

    2000-03-01

    The history of the application of statistical theory to the analysis of clinical trials is reviewed. The current orthodoxy is a somewhat illogical hybrid of the original theory of significance tests of Edgeworth, Karl Pearson, and Fisher, and the subsequent decision theory approach of Neyman, Egon Pearson, and Wald. This hegemony is under threat from Bayesian statisticians. A third approach is that of likelihood, stemming from the work of Fisher and Barnard. This approach is illustrated using hypothetical data from the Lancet articles by Bradford Hill, which introduced clinicians to statistical theory.

  13. Failed Pediatric Drug Development Trials.

    PubMed

    Momper, J D; Mulugeta, Y; Burckart, G J

    2015-09-01

    Pediatric product development initiatives have stimulated the development of therapies for children, resulting in improved product labeling, increased identification of adverse events, and development of new pediatric formulations. However, 42% of recently completed pediatric trials have failed to establish either safety or efficacy, leading to an inability to label the product for use in children.(1) Characterizing these failed trials, including common contributing factors, is imperative to designing better pediatric trials in the future. © 2015 American Society for Clinical Pharmacology and Therapeutics.

  14. The Styx field trial

    PubMed Central

    Gemmell, M. A.

    1968-01-01

    An assessment was made of the effectiveness of the generally accepted methods recommended for controlling hydatid disease during the course of a field-trial, initiated in 1943 in an isolated region of New Zealand. The results obtained during the first 21 years are described. Basically, the trial was an attempt to compare the effectiveness of a general public health educational programme and an anthelmintic programme using arecoline hydrobromide for treatment of dogs with that of a specific educational programme using this compound as a diagnostic agent. Arecoline hydrobromide was found to be too uncertain in its action to be of practical value as an anthelmintic. The development of diagnostic techniques, described in this paper, made it possible to use the compound for diagnostic purposes and thus for educational purposes, since each dog could be examined for tapeworms in the presence of the owner. Using changes in the annual prevalence rate in sheep of the cysts of E. granulosus and those of T. hydatigena as the principal indicators, the conclusion has been reached that the specific diagnostic approach achieved more success than the general educational and treatment programme. The principal reason for this appears to be that the former approach induced a greater awareness in owners of the need for strict management to prevent dogs gaining access to infective raw offal than that stimulated in the community when the dogs were dosed but not examined. ImagesFIG. 2FIG. 4FIG. 5 PMID:5303843

  15. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran.

  16. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adalimumab, alefacept, alemtuzumab, almotriptan, AMGN-0007, anakinra, anti-CTLA-4 Mab, L-arginine hydrochloride, arzoxifene hydrochloride, astemizole, atazanavir sulfate, atlizumab; Belimumab, BG-9928, binodenoson, bosentan, botulinum toxin type B, bovine lactoferrin, BufferGel; Caspofungin acetate, ciclesonide,cilomilast, ciluprevir, clofarabine, CVT-3146; Darbepoetin alfa, desloratadine, diflomotecan, doripenem, dronedarone hydrochloride, drotrecogin alfa (activated), DT388-GM-CSF, duloxetine hydrochloride, E-5564, efalizumab, enfuvirtide, esomeprazole magnesium, estradiol acetate, ETC-642, exenatide, exisulind, ezetimib; Febuxostat; Gallium maltolate, ganirelix acetate, garenoxacin mesilate, gefitinib; H11, HuMax; IL-15, IDD-1, IGIV-C, imatinib mesylate, ISIS-14803, ITF-1697, ivabradine hydrochloride; KRN-5500; L-365260, levetiracetam, levosimendan, licofelone, linezolid, LJP-1082, lopinavir lumiracoxib; MCC-478, melatonin, morphine hydrochloride, morphine-6-glucuronide, moxidectin; N-Acetylcarnosine, natalizumab, NM-702, NNC-05-1869, NSC-703940; Ocinaplon OM-89, omalizumab, omeprazole/ sodium bicarbonate, OPC-28326, ospemifene; PEG-filgrastim peginterferon alfa-2a, pegsunercept, pirfenidone, pralmorelin, pregabalin; Recombinant glucagon-like peptide-1 (7-36) amide, repifermin, RSD-1235; S-8184, selodenoson, sodium dichloroacetate, suberanilohydroxamic acid; TAS-102, terfenadine, teriparatide, tipranavir troxacitabine; Ximelagatran; YM-337. (c) 2003 Prous Science

  18. Gateways to Clinical Trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2003-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 2F5, 2G12, abetimus sodium, ABI-007, adalimumab, adefovir dipivoxil, AE-941, alefacept, altropane, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminopterin, anakinra, aprinocarsen sodium, atazanavir, atlizumab, atomoxetine hydrochloride; B7-1 vaccine, bevacizumab, biricodar dicitrate, BMS-188667, brasofensine sulfate, bryostatin 1; cantuzumab mertansine, CHS-828, cinacalcet hydrochloride, cipamfylline, creatine, CVT-3146; darbepoetin alfa, DITPA, drotrecogin alfa (activated), duloxetine hydrochloride; edatrexate, efalizumab, ENMD-0997, epoetin, erlosamide, esomeprazole magnesium, etiprednol dicloacetate, etoricoxib, everolimus, ezetimibe; fampridine, fenretinide, FTY-720; IGF-I/IGFBP-3, IL-1 cytokine trap, ilodecakin, interferon beta, ISIS-104838, ISIS-2503, ISIS-5132, ivabradine hydrochloride; lafutidine, lanthanum carbonate, l-Arginine hydrochloride, LEA29Y, lerdelimumab, levetiracetam, levobupivacaine hydrochloride, levosimendan, lopinavir; melagatran, mibefradil hydrochloride, miglustat, morphine-6-glucuronide; nesiritide; omalizumab, omapatrilat; p24-VLP, parecoxib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pitavastatin calcium, plevitrexed, prasterone, pregabalin, PRO-2000, prucalopride; rapacuronium bromide, rebimastat, RGA-0853, rubitecan, ruboxistaurin mesilate hydrate, RWJ-67657; S-16020-2, sarizotan, SLV-306, stiripentol; TA-CIN, tenecteplase, teriparatide, tezacitabine, tipifarnib, trabectedin, troglitazone; valdecoxib, vardenafil; Z-338, ziconotide.

  20. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2003-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AdGVVEGF121.10, anakinra, andolast, anidulafungin, APC-2059, l-arginine hydrochloride, aripiprazole, arzoxifene hydrochloride, asimadoline; Bexarotene, bimatoprost, bimosiamose, bizelesin, BMS-188667, botulinum toxin type B, bromfenac sodium, bryostatin 1; Cannabidiol, cariporide mesilate, CCI-1004, CDP-571, cerivastatin sodium, clevudine; Dalbavancin, darbepoetin alfa, decitabine, deligoparin sodium, diethylnorspermine, drotrecogin alfa (activated), DTaP-HBV-IPV/Hib-vaccine; E-5564, eculizumab, edodekin alfa, emtricitabine, enfuvirtide, (-)-epigallocatechin gallate, eplerenone, esomeprazole magnesium, etaquine, etoricoxib, ezetimibe; Fesoterodine, fipamezole hydrochloride, fondaparinux sodium, fosamprenavir calcium, frovatriptan, fulvestrant; Gadofosveset sodium, galiximab, ghrelin (human), glufosfamide; Homoharringtonine; Idraparinux sodium, imatinib mesylate, INS-37217; KRN-7000; L-651582, lafutidine, lanthanum carbonate, lenercept, levetiracetam, lusupultide; Magnesium sulfate, melatonin, mepolizumab, midostaurin, morphine hydrochloride, mozavaptan; Natalizumab, nesiritide; OPC-51803, oregovomab, oritavancin; Peginterferon alfa-2(a), pleconaril, plevitrexed, prasterone, pregabalin; Ranibizumab, Ro-31-7453, roxifiban acetate, rubitecan; SCV-07, SHL-749, sho-saiko-to, soblidotin, solifenacin succinate; Tegaserod maleate, telithromycin, tenecteplase, theraCIM, tipifarnib, travoprost; Valdecoxib, vardenafil hydrochloride hydrate, voriconazole; Ximelagatran; Ziprasidone hydrochloride, ZYC-00101. (c) 2003 Prous Science. All rights reserved.

  1. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2002-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abciximab, acetylcysteine, adefovir dipivoxil, alfuzosin hydrochloride, aliskiren fumarate, alosetron hydrochloride, amlodipine besilate, apomorphine hydrochloride, atazanavir, atorvastatin, atorvastatin calcium, atrasentan; Basiliximab, beraprost sodium, bevacizumab, bivalirudin, botulinum toxin type A, botulinum toxin type B; Celecoxib, cetuximab, cilansetron, cilomilast; Daclizumab, darbepoetin alfa, docetaxel, duloxetine hydrochloride; Efalizumab, efavirenz, eletriptan,, entecavir, eplerenone, epoetin alfa, eptifibatide, esomeprazole magnesium. ezetimibe; Filgrastim, finasteride, fluvastatin sodium, follitropin alfa; Gemcitabine, gemeprost, ghrelin (human); HE-2000; Infliximab, 111In-Pentetreotide, interferon alfa-2 alpha, interferon alfa-2 beta, interferon beta-1 alpha, irbesartan, irinotecan hydrochloride; Ketamine hydrochloride; L-778123, lafutidine, lamivudine, lamivudine/zidovudine, latanoprost, letrozole, licofelone, lopinavir, losartan potassium, loxiglumide, lubeluzole; Magnesium sulfate, MeGLA, meloxicam, mycophenolate mofetil; NBI-6024, nelfinavir mesilate, nesiritide, nevirapine, niacin, NN-2211; Octreotide, orlistat; PC-515, peginterferon alfa-2 alpha, peginterferon alfa-2b, pemetrexed disodium, pibrozelesin hydrochloride, pimagedine, pirfenidone, pitavastatin calcium, premarin/trimegestone, prucalopride; Rabeprazole sodium; reboxetine, risedronate sodium, ritonavir, rituximab, rofecoxib, roflumilast, rosuvastatin calcium; Sertraline, sibutramine hydrochloride monohydrate, sildenafil citrate, spironolactone, stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride

  2. Bayesian Clinical Trials in Action

    PubMed Central

    Lee, J. Jack; Chu, Caleb T.

    2012-01-01

    Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. The alternative Bayesian paradigm has been greatly enhanced by advancements in computational algorithms and computer hardware. Compared to its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and for studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation, and analysis, and Web-based applications, which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More such trials should be designed and conducted to refine the approach and demonstrate its real benefit in action. PMID:22711340

  3. Bayesian clinical trials in action.

    PubMed

    Lee, J Jack; Chu, Caleb T

    2012-11-10

    Although the frequentist paradigm has been the predominant approach to clinical trial design since the 1940s, it has several notable limitations. Advancements in computational algorithms and computer hardware have greatly enhanced the alternative Bayesian paradigm. Compared with its frequentist counterpart, the Bayesian framework has several unique advantages, and its incorporation into clinical trial design is occurring more frequently. Using an extensive literature review to assess how Bayesian methods are used in clinical trials, we find them most commonly used for dose finding, efficacy monitoring, toxicity monitoring, diagnosis/decision making, and studying pharmacokinetics/pharmacodynamics. The additional infrastructure required for implementing Bayesian methods in clinical trials may include specialized software programs to run the study design, simulation and analysis, and web-based applications, all of which are particularly useful for timely data entry and analysis. Trial success requires not only the development of proper tools but also timely and accurate execution of data entry, quality control, adaptive randomization, and Bayesian computation. The relative merit of the Bayesian and frequentist approaches continues to be the subject of debate in statistics. However, more evidence can be found showing the convergence of the two camps, at least at the practical level. Ultimately, better clinical trial methods lead to more efficient designs, lower sample sizes, more accurate conclusions, and better outcomes for patients enrolled in the trials. Bayesian methods offer attractive alternatives for better trials. More Bayesian trials should be designed and conducted to refine the approach and demonstrate their real benefit in action.

  4. [Critical reading of clinical trials].

    PubMed

    Aptel, F; Cucherat, M; Blumen-Ohana, E; Denis, P

    2011-12-01

    Clinical trials are playing an increasingly crucial role in modern evidence based medicine, allowing for rigorous scientific evaluation of treatment strategies and validation of patient care. The results of clinical trials often form the rational basis from which physicians draw information used to adapt their therapeutic practices. Critical reading and analysis of trials involves the assessment of whether the available data provide enough credible evidence that the treatment will result in a clinically significant and relevant improvement. Evaluating the quality of a clinical trial is a process that draws upon sometimes complex methodological and statistical concepts, with which the reader should nonetheless be familiar in order to come to impartial conclusions regarding the raw data presented in the clinical trials. The goal of the current article is to review the methodological and statistical concepts required for the design and interpretation of clinical trials, so as to allow for a critical analysis of publications or presentations of clinical trials. The first section describes the major methodological principles of clinical trial design required for a rigorous evaluation of the treatment benefit, as well as the various pitfalls or biases that could lead to erroneous conclusions. The second section briefly describes the main statistical tests used in clinical trials, as well as certain situations that may increase the risk of false positive findings (type 1 error), such as multiple, subgroup, intermediate and non-inferiority analysis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  5. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T

  6. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa

  7. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium

  8. Vicarious trial and error

    PubMed Central

    Redish, A. David

    2016-01-01

    When rats come to a decision point, they sometimes pause and look back and forth as if deliberating over the choice; at other times, they proceed as if they have already made their decision. In the 1930s, this pause-and-look behaviour was termed ‘vicarious trial and error’ (VTE), with the implication that the rat was ‘thinking about the future’. The discovery in 2007 that the firing of hippocampal place cells gives rise to alternating representations of each of the potential path options in a serial manner during VTE suggested a possible neural mechanism that could underlie the representations of future outcomes. More-recent experiments examining VTE in rats suggest that there are direct parallels to human processes of deliberative decision making, working memory and mental time travel. PMID:26891625

  9. The FESTER field trial

    NASA Astrophysics Data System (ADS)

    van Eijk, Alexander M. J.; Gunter, Willie H.; February, Faith J.; Maritz, Benita; Vrahimis, George; Koago, Mokete S.; Wainman, Carl; Eisele, Christian; Seiffer, Dirk; Sucher, Erik; Stein, Karin; van Iersel, Miranda; Cohen, Leo H.; Van Binsbergen, Sven A.; Heemskerk, H. J. M. (Eric); Sternberg, A.; Schulte, H.; van Rheenen, Arthur D.; Brenthagen, Erik; Thomassen, Jan B.; Griffith, D.

    2016-09-01

    An overview is given of the First European - South African Transmission ExpeRiment (FESTER), which took place in South Africa, over the False Bay area, centered around Simon's Town. The experiment lasted from April 2015 through February 2016 and involved continuous observations as well as periodic observations that took place during four Intensive Observation Periods (IOPs) of 2 weeks each, which were spread over the year. The continuous observations aimed at a characterization of the electro-optical propagation environment, and included standard meteorology, aerosol, refraction and turbulence measurements. The periodic observations aimed at assessing the performance of electro-optical sensors in VIS / SWIR / MWIR and LWIR wavebands by following a boat sailing outbound and inbound tracks. In addition, dynamic aspects of electro-optical signatures, i.e., the changes induced by variations in the environment and/or target orientation, were studied. The present paper provides an overview of the trial, and presents a few first results.

  10. Dramatization of Salem Witch Trial.

    ERIC Educational Resources Information Center

    Chorak, Elizabeth

    1988-01-01

    Presents a lesson which can provide elementary students with an opportunity to compare fair and unfair trials. Stating that the lesson works best if an attorney is used as a resource person, the plan includes a short play about a Salem, Massachusetts witch trial and follow-up questions to stimulate student discussion. (GEA)

  11. Clinical trials in cancer research.

    PubMed Central

    Gehan, E A

    1979-01-01

    This is a review paper which gives a discussion of various aspects of clinical trials in cancer research. Since the conduct of the first randomized controlled clinical trial in cancer patients in the mid-1950's, substantial progress has been made in the utilization of the clinical trial technique for the evaluation of therapeutic efficiacy. The important elements of a protocol are given with some discussion of items to be considered in designing a protocol. The types of clinical trial (phase I, II, III) are defined, and the place of each phase of study in the context of the search for new treatments is delineated. A comprehensive discussion is given of the elements in the comparative clinical trial (phase III), including objectives, consierations in planning (comparability of treatment groups stratification of patients, feasibility and size of study, and prospective versus retrospective studies). Brief descriptions are given of designs for comparative clinical trials and a trial in oat cell lung carcinoma is discussed in some detail. Finally, some comments and references are given concerning the analysis of clinical trials. PMID:232043

  12. Dramatization of Salem Witch Trial.

    ERIC Educational Resources Information Center

    Chorak, Elizabeth

    1988-01-01

    Presents a lesson which can provide elementary students with an opportunity to compare fair and unfair trials. Stating that the lesson works best if an attorney is used as a resource person, the plan includes a short play about a Salem, Massachusetts witch trial and follow-up questions to stimulate student discussion. (GEA)

  13. Trial Rights of the Accused.

    ERIC Educational Resources Information Center

    Bodenhamer, David J.

    1990-01-01

    Examines the origins of the U. S. Bill of Rights and constitutional guarantees, focusing on trial rights, tracing them to English antecedents and the colonial period. Explains changes in understanding and the application of trial rights, highlighting the U.S. Supreme Court's evolving influence since the nineteenth century. Outlines contemporary…

  14. Defendants' Rights in Criminal Trials.

    ERIC Educational Resources Information Center

    Martin, Ralph C., II; Keeley, Elizabeth

    1997-01-01

    Reviews the protections afforded by the Constitution for defendants in criminal trials. These include the right to a jury trial (in cases of possible incarceration), an impartial jury, and the requirement of a unanimous verdict. Defends the use of plea bargaining as essential to an efficient criminal justice system. (MJP)

  15. LTDNA Evidence on Trial

    PubMed Central

    Roberts, Paul

    2016-01-01

    Adopting the interpretative/hermeneutical method typical of much legal scholarship, this article considers two sets of issues pertaining to LTDNA profiles as evidence in criminal proceedings. The section titled Expert Evidence as Forensic Epistemic Warrant addresses some rather large questions about the epistemic status and probative value of expert testimony in general. It sketches a theoretical model of expert evidence, highlighting five essential criteria: (1) expert competence; (2) disciplinary domain; (3) methodological validity; (4) materiality; and (5) legal admissibility. This generic model of expert authority, highlighting law's fundamentally normative character, applies to all modern forms of criminal adjudication, across Europe and farther afield. The section titled LTDNA Evidence in UK Criminal Trials then examines English and Northern Irish courts' attempts to get to grips with LTDNA evidence in recent cases. Better appreciating the ways in which UK courts have addressed the challenges of LTDNA evidence may offer some insights into parallel developments in other legal systems. Appellate court rulings follow a predictable judicial logic, which might usefully be studied and reflected upon by any forensic scientist or statistician seeking to operate effectively in criminal proceedings. Whilst each legal jurisdiction has its own unique blend of jurisprudence, institutions, cultures and historical traditions, there is considerable scope for comparative analysis and cross-jurisdictional borrowing and instruction. In the spirit of promoting more nuanced and sophisticated international interdisciplinary dialogue, this article examines UK judicial approaches to LTDNA evidence and begins to elucidate their underlying institutional logic. Legal argument and broader policy debates are not confined to considerations of scientific validity, contamination risks and evidential integrity, or associated judgments of legal admissibility or exclusion. They also crucially

  16. LTDNA Evidence on Trial.

    PubMed

    Roberts, Paul

    2016-01-01

    Adopting the interpretative/hermeneutical method typical of much legal scholarship, this article considers two sets of issues pertaining to LTDNA profiles as evidence in criminal proceedings. The section titled Expert Evidence as Forensic Epistemic Warrant addresses some rather large questions about the epistemic status and probative value of expert testimony in general. It sketches a theoretical model of expert evidence, highlighting five essential criteria: (1) expert competence; (2) disciplinary domain; (3) methodological validity; (4) materiality; and (5) legal admissibility. This generic model of expert authority, highlighting law's fundamentally normative character, applies to all modern forms of criminal adjudication, across Europe and farther afield. The section titled LTDNA Evidence in UK Criminal Trials then examines English and Northern Irish courts' attempts to get to grips with LTDNA evidence in recent cases. Better appreciating the ways in which UK courts have addressed the challenges of LTDNA evidence may offer some insights into parallel developments in other legal systems. Appellate court rulings follow a predictable judicial logic, which might usefully be studied and reflected upon by any forensic scientist or statistician seeking to operate effectively in criminal proceedings. Whilst each legal jurisdiction has its own unique blend of jurisprudence, institutions, cultures and historical traditions, there is considerable scope for comparative analysis and cross-jurisdictional borrowing and instruction. In the spirit of promoting more nuanced and sophisticated international interdisciplinary dialogue, this article examines UK judicial approaches to LTDNA evidence and begins to elucidate their underlying institutional logic. Legal argument and broader policy debates are not confined to considerations of scientific validity, contamination risks and evidential integrity, or associated judgments of legal admissibility or exclusion. They also crucially

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  19. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 81C6; Adefovir dipivoxil, Agalsidase alfa, AGM-1470, albumin interferon alfa, alefacept, alosetron hydrochloride, anakinra, anti-CTLA-4 Mab, aprepitant, aripiprazole, atazanavir; BAY-43-9006, BBR-3438, beta-L-Fd4C, bimatoprost, bortezomib, bosentanBR96-doxorubicin; Caspofungin acetate, ciclesonide, cilengitide, cilomilast, COL-1621, COL-3, CpG-7909, cyclosporine; DCVax-Brain, dexmethylphenidate hydrochloride, dexosome vaccine (melanoma), donepezil hydrochloride, drotrecogin alfa (activated), DTI-015, [99Tc]-DTPA-mannosyldextran, duloxetine hydrochloride; Emivirine, emtricitabine, entecavir, epothilone B, estradiol-MNP, etonogestrel/etonogestrel/ethinylestradiol, etoricoxib; Febuxostat, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GVS-111; Heparinase I, HspE7, human alpha-glucosidase, human insulin; Imatinib mesylate, INGN-241, interferon alfa B/D hybrid, interferon alfa Biphasix, ISIS-14803; Lanicemine hydrochloride, 1311-lipiodol, liposome-encapsulated mitoxantrone, lixivaptan, lumiracoxib, lupus-AHP, LY-466700; Marimastat, MEN-10755, micafungin sodium; Nitronaproxen, NSC-683864 Omalizumab, oral insulin; Palonosetron hydrochloride, peginterferon alfa-2a, pimecrolimus, pralnacasan, pramlintide acetate, pregabalin, pyrazoloacridine; R-165335, ranolazine, risperidone, RPR-109881;, RSD-1235, Satraplatin, seocalcitol, sertindole, SMART anti-interferon gamma antibody, sulfasalazine; T-138067, TAK-013, tegaserod maleate, telithromycin, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, TP-38; Valdecoxib, vatalanib succinate, voriconazole; ZD-9331.

  1. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  2. Imaging in Endovascular Stroke Trials

    PubMed Central

    Malhotra, Konark; Liebeskind, David S

    2015-01-01

    Ischemic stroke remains a leading cause of death and disability worldwide. Various endovascular trials have addressed clinical outcomes without elucidating the impact of imaging studies in patient selection. The success of recent endovascular trials was bolstered by the use of advanced imaging techniques for optimal selection of reperfusion candidates. This seminal juncture in the history of stroke trials warrants further consideration on the use of imaging to guide future refinements in the treatment of acute stroke. In this article, we systematically review the imaging methodology and key facets used in all published endovascular stroke trials to date, discuss the success of recent trials using latest advanced imaging techniques and focus on the importance of imaging studies for future patient selection. PMID:26179500

  3. Experimental studies: randomized clinical trials.

    PubMed

    Gjorgov, A N

    1998-01-01

    There are two major approaches to medical investigations: observational studies and experimental trials. The classical application of the experimental design to studies of human populations is the randomized clinical trial of the efficacy of a new drug or treatment. A further application of the experimental studies is to the testing of hypotheses about the etiology of a disease, already tested and corroborated from various forms of observational studies. Ethical considerations and requirements for consent of the experimental subjects are of primary concern in the clinical trials, and those concerns set the first and final limits for implementing a trial. General moral principles in research with human and animal beings, defined by the "Nuremberg Code," deal with strict criteria for approval, endorsement and evaluation of a clinical trial.

  4. Clinical Trials, a Healthier Future for All

    MedlinePlus

    ... Clinical Trials Clinical Trials, A Healthier Future for All Past Issues / Fall 2016 Table of Contents Did ... be harmed by, the treatment. Most, but not all, clinical trials in the U.S. are approved and ...

  5. HIV/AIDS Clinical Trials Fact Sheet

    MedlinePlus

    ... and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help researchers ... to HIV Can anyone participate in an HIV/AIDS clinical trial? It depends on the study. Some ...

  6. Clinical Trials | Division of Cancer Prevention

    Cancer.gov

    Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

  7. Using simulation to aid trial design: Ring-vaccination trials

    PubMed Central

    Hitchings, Matt David Thomas; Grais, Rebecca Freeman

    2017-01-01

    Background The 2014–6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination. Methods and findings We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design. Conclusions Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring

  8. Quality Assurance for Clinical Trials

    PubMed Central

    Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.

    2013-01-01

    Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352

  9. Social media in clinical trials.

    PubMed

    Thompson, Michael A

    2014-01-01

    Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.

  10. Randomized phase II clinical trials.

    PubMed

    Jung, Sin-Ho; Sargent, Daniel J

    2014-01-01

    Traditionally, Phase II trials have been conducted as single-arm trials to compare the response probabilities between an experimental therapy and a historical control. Historical control data, however, often have a small sample size, are collected from a different patient population, or use a different response assessment method, so that a direct comparison between a historical control and an experimental therapy may be severely biased. Randomized Phase II trials entering patients prospectively to both experimental and control arms have been proposed to avoid any bias in such cases. The small sample sizes for typical Phase II clinical trials imply that the use of exact statistical methods for their design and analysis is appropriate. In this article, we propose two-stage randomized Phase II trials based on Fisher's exact test, which does not require specification of the response probability of the control arm for testing. Through numerical studies, we observe that the proposed method controls the type I error accurately and maintains a high power. If we specify the response probabilities of the two arms under the alternative hypothesis, we can identify good randomized Phase II trial designs by adopting the Simon's minimax and optimal design concepts that were developed for single-arm Phase II trials.

  11. Trial analytics--a tool for clinical trial management.

    PubMed

    Bose, Anindya; Das, Suman

    2012-01-01

    Prolonged timelines and large expenses associated with clinical trials have prompted a new focus on improving the operational efficiency of clinical trials by use of Clinical Trial Management Systems (CTMS) in order to improve managerial control in trial conduct. However, current CTMS systems are not able to meet the expectations due to various shortcomings like inability of timely reporting and trend visualization within/beyond an organization. To overcome these shortcomings of CTMS, clinical researchers can apply a business intelligence (BI) framework to create Clinical Research Intelligence (CLRI) for optimization of data collection and analytics. This paper proposes the usage of an innovative and collaborative visualization tool (CTA) as CTMS "add-on" to help overwhelm these deficiencies of traditional CTMS, with suitable examples.

  12. Modeling trial by trial and block feedback in perceptual learning

    PubMed Central

    Liu, Jiajuan; Dosher, Barbara; Lu, Zhong-Lin

    2014-01-01

    Feedback has been shown to play a complex role in visual perceptual learning. It is necessary for performance improvement in some conditions while not others. Different forms of feedback, such as trial-by-trial feedback or block feedback, may both facilitate learning, but with different mechanisms. False feedback can abolish learning. We account for all these results with the Augmented Hebbian Reweight Model (AHRM). Specifically, three major factors in the model advance performance improvement: the external trial-by-trial feedback when available, the self-generated output as an internal feedback when no external feedback is available, and the adaptive criterion control based on the block feedback. Through simulating a comprehensive feedback study (Herzog & Fahle 1997, Vision Research, 37 (15), 2133–2141), we show that the model predictions account for the pattern of learning in seven major feedback conditions. The AHRM can fully explain the complex empirical results on the role of feedback in visual perceptual learning. PMID:24423783

  13. Bayes' postulate for trinomial trials

    NASA Astrophysics Data System (ADS)

    Diniz, M. A.; Polpo, A.

    2012-10-01

    In this paper, we discuss Bayes' postulate and its interpretation. We extend the binomial trial method proposed by de Finetti [1] to trinomial trials, for which we argue that the consideration of equiprobability a priori for the possible outcomes of the trinomial trials implies that the parameter vector has Dirichlet(1,1) as prior. Based on this result, we agree with Stigler [2] in that the notion in Bayes' postulate stating "absolutely know nothing" is related to the possible outcomes of an experiment and not to "non-information" about the parameter.

  14. Designing clinical trials for amblyopia

    PubMed Central

    Holmes, Jonathan M.

    2015-01-01

    Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. PMID:25752747

  15. Designing clinical trials for amblyopia.

    PubMed

    Holmes, Jonathan M

    2015-09-01

    Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Data fraud in clinical trials

    PubMed Central

    George, Stephen L; Buyse, Marc

    2015-01-01

    Highly publicized cases of fabrication or falsification of data in clinical trials have occurred in recent years and it is likely that there are additional undetected or unreported cases. We review the available evidence on the incidence of data fraud in clinical trials, describe several prominent cases, present information on motivation and contributing factors and discuss cost-effective ways of early detection of data fraud as part of routine central statistical monitoring of data quality. Adoption of these clinical trial monitoring procedures can identify potential data fraud not detected by conventional on-site monitoring and can improve overall data quality. PMID:25729561

  17. The ethics of clinical trials.

    PubMed Central

    Wing, J K

    1975-01-01

    In summary, the discussion by Professors Helmchen and Müller-Oerlinghausen of the morality of clinical trials has emphasized a point that is frequently overlooked. It is an essential to consider those situations in which it might be unethical not to conduct a trial as it is to be concerned about the ways in which trials might restrict the rights of the individuals taking part in them. They and I have dealt mainly with the first of these two issues because it has been relatively neglected. The second is, of course, equally important and has rightly received much attention. Both matters deserve further public discussion. PMID:775090

  18. The ethics of clinical trials.

    PubMed

    Wing, J K

    1975-12-01

    In summary, the discussion by Professors Helmchen and Müller-Oerlinghausen of the morality of clinical trials has emphasized a point that is frequently overlooked. It is an essential to consider those situations in which it might be unethical not to conduct a trial as it is to be concerned about the ways in which trials might restrict the rights of the individuals taking part in them. They and I have dealt mainly with the first of these two issues because it has been relatively neglected. The second is, of course, equally important and has rightly received much attention. Both matters deserve further public discussion.

  19. Clinical trials in neonatal sepsis.

    PubMed

    Oeser, Clarissa; Lutsar, Irja; Metsvaht, Tuuli; Turner, Mark A; Heath, Paul T; Sharland, Mike

    2013-12-01

    Antibiotic licensing studies remain a problem in neonates. The classical adult clinical syndrome-based licensing studies do not apply to neonates, where sepsis is the most common infection. The main obstacle to conducting neonatal antibiotic trials is a lack of consensus on the definition of neonatal sepsis itself and the selection of appropriate endpoints. This article describes the difficulties of the clinical and laboratory definitions of neonatal sepsis and reviews the varying designs of previous neonatal sepsis trials. The optimal design of future trials of new antibiotics will need to be based on pharmacokinetic/pharmacodynamic parameters, combined with adequately powered clinical studies to determine safety and efficacy.

  20. Behavioral Therapies Trials

    PubMed Central

    Marcus, Marianne T.; Liehr, Patricia R.; Schmitz, Joy; Moeller, F. Gerald; Swank, Paul; Fine, Micki; Cron, Stanley; Granmayeh, L. Kian; Carroll, Deidra D.

    2008-01-01

    Background: Behavior change is integral to the prevention and treatment of many disorders associated with deleterious lifestyles. Rigorous scientific testing of behavior change interventions is an important goal for nursing research. Approach: The stage model for behavioral therapy development is recommended as a useful framework for evaluating behavior change strategies. The NIH model specifies three stages from initial testing of novel behavioral therapies to their dissemination in community settings. Definitions of each step in a Stage I trial and a case example of Mindfulness-Based Stress Reduction (MBSR) in therapeutic community treatment are provided. Results: It is feasible to adapt a behavioral therapy such as MBSR using the stage model framework. Steps in the process include: (a) determining pilot study design and describing the population; (b) modifying the intervention and developing the manual; (c) training the teachers; (d) implementing a pilot study; and (e) monitoring treatment integrity. Discussion: The development of behavior therapies requires the same scientific rigor used in pharmacotherapy research. Stage I of the model enables consideration of the “dose” of a behavioral intervention necessary to achieve behavior change in a defined population. The stage model offers an excellent approach to achieving rigor in a variety of potentially useful therapies of interest to nurse researchers. PMID:17495577

  1. The Dynamo Clinical Trial

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas R.

    2016-04-01

    The Dynamo Clinical Trial evaluates long-term stellar magnetic health through periodic X-ray examinations (by the Chandra Observatory). So far, there are only three subjects enrolled in the DTC: Alpha Centauri A (a solar-like G dwarf), Alpha Cen B (an early K dwarf, more active than the Sun), and Alpha Canis Majoris A (Procyon, a mid-F subgiant similar in activity to the Sun). Of these, Procyon is a new candidate, so it is too early to judge how it will fare. Of the other two, Alpha Cen B has responded well, with a steady magnetic heartbeat of about 8 years duration. The sickest of the bunch, Alpha Cen A, was in magnetic cardiac arrest during 2005-2010, but has begun responding to treatment in recent years, and seems to be successfully cycling again, perhaps achieving a new peak of magnetic health in the 2016 time frame. If this is the case, it has been 20 years since A's last healthful peak, significantly longer than the middle-aged Sun's 11-year magnetic heartbeat, but perhaps in line with Alpha Cen A's more senescent state (in terms of "relative evolutionary age," apparently an important driver of activity). (By the way, don't miss the exciting movie of the Alpha Cen stars' 20-year X-ray dance.)

  2. The Virtual Trial

    PubMed Central

    de Haan, Willem

    2017-01-01

    Although brain network analysis in neurodegenerative disease is still a fairly young discipline, expectations are high. The robust theoretical basis, the straightforward detection and explanation of otherwise intangible complex system phenomena, and the correlations of network features with pathology and cognitive status are qualities that show the potential power of this new instrument. We expect “connectomics” to eventually better explain and predict that essential but still poorly understood aspect of dementia: the relation between pathology and cognitive symptoms. But at this point, our newly acquired knowledge has not yet translated into practical methods or applications in the medical field, and most doctors regard brain connectivity analysis as a wonderful but exotic research niche that is too technical and abstract to benefit patients directly. This article aims to provide a personal perspective on how brain connectivity research may get closer to obtaining a clinical role. I will argue that network intervention modeling, which unites the strengths of network analysis and computational modeling, is a great candidate for this purpose, as it can offer an attractive test environment in which positive and negative influences on network integrity can be explored, with the ultimate aim to find effective countermeasures against neurodegenerative network damage. The virtual trial approach might become what both dementia and connectivity researchers have been waiting for: a versatile tool that turns our growing connectome knowledge into clinical predictions. PMID:28326011

  3. GAUSS Project Trials Results

    NASA Astrophysics Data System (ADS)

    Di Fazio, Antonella; Vernucci, Antonio; Rossini, Eugenio

    2003-07-01

    the Consortium Partners. The former ones constitute the ground and space segments, the latter ones include the advanced user terminal and the applications. The assembled system was used as test-bed during the trail campaign, to validate and prove the provided services and developed applications.The GAUSS Demonstrator includes the following components:ß The Mobile User Terminal installed on a car (van) or on a boat. An innovative multi-mode user equipment was developed, consisting of the following main components:- An integrated NAV / COM digital receive front-end (DFRE), able to de-multiplex the NAV signals (the current GNSS1 band and the simulated Galileo bands), and the COM signal in the S-UMTS band;- For COM: a transmit front-end, and a baseband & control section operating in CDMA and supporting the upper protocol layers (UMTS packet transmission standard based - for short packet); a RF subsystem, including the L→S bands conversion;- For NAV: a GNSS (GPS, EGNOS) navigation receiver, the GNSS1 System (MTB - Mediterranean Test bed, ESTB / EGNOS System Test Bed) for navigation;* The Communication capacity on the INMARSAT 3F5 Satellite* The Gateway, located in LARIO Telespazio premises* The Lario07 Station* The Service Centre* The Service Provider.The GAUSS Demonstrator reflects all the main elements of a complete user platform for service provisioning: mobility assistance, safety and transport efficient management are the core of the developed applications. Applications were developed, specifically to provide reliable and effective services to the citizens: road info-mobility and fleet management, inland waterways vessel traffic management and information, port/terminals appointment monitoring & control, dangerous goods transhipment supervision, emergency assistance.A trial campaign, run into real environments, was performed in Summer 2002. GAUSS Demonstrator performances and benefits were validated with the direct involvement of an inter-modal transport user

  4. Modelling Trial-by-Trial Changes in the Mismatch Negativity

    PubMed Central

    Lieder, Falk; Daunizeau, Jean; Garrido, Marta I.; Friston, Karl J.; Stephan, Klaas E.

    2013-01-01

    The mismatch negativity (MMN) is a differential brain response to violations of learned regularities. It has been used to demonstrate that the brain learns the statistical structure of its environment and predicts future sensory inputs. However, the algorithmic nature of these computations and the underlying neurobiological implementation remain controversial. This article introduces a mathematical framework with which competing ideas about the computational quantities indexed by MMN responses can be formalized and tested against single-trial EEG data. This framework was applied to five major theories of the MMN, comparing their ability to explain trial-by-trial changes in MMN amplitude. Three of these theories (predictive coding, model adjustment, and novelty detection) were formalized by linking the MMN to different manifestations of the same computational mechanism: approximate Bayesian inference according to the free-energy principle. We thereby propose a unifying view on three distinct theories of the MMN. The relative plausibility of each theory was assessed against empirical single-trial MMN amplitudes acquired from eight healthy volunteers in a roving oddball experiment. Models based on the free-energy principle provided more plausible explanations of trial-by-trial changes in MMN amplitude than models representing the two more traditional theories (change detection and adaptation). Our results suggest that the MMN reflects approximate Bayesian learning of sensory regularities, and that the MMN-generating process adjusts a probabilistic model of the environment according to prediction errors. PMID:23436989

  5. Modelling trial-by-trial changes in the mismatch negativity.

    PubMed

    Lieder, Falk; Daunizeau, Jean; Garrido, Marta I; Friston, Karl J; Stephan, Klaas E

    2013-01-01

    The mismatch negativity (MMN) is a differential brain response to violations of learned regularities. It has been used to demonstrate that the brain learns the statistical structure of its environment and predicts future sensory inputs. However, the algorithmic nature of these computations and the underlying neurobiological implementation remain controversial. This article introduces a mathematical framework with which competing ideas about the computational quantities indexed by MMN responses can be formalized and tested against single-trial EEG data. This framework was applied to five major theories of the MMN, comparing their ability to explain trial-by-trial changes in MMN amplitude. Three of these theories (predictive coding, model adjustment, and novelty detection) were formalized by linking the MMN to different manifestations of the same computational mechanism: approximate Bayesian inference according to the free-energy principle. We thereby propose a unifying view on three distinct theories of the MMN. The relative plausibility of each theory was assessed against empirical single-trial MMN amplitudes acquired from eight healthy volunteers in a roving oddball experiment. Models based on the free-energy principle provided more plausible explanations of trial-by-trial changes in MMN amplitude than models representing the two more traditional theories (change detection and adaptation). Our results suggest that the MMN reflects approximate Bayesian learning of sensory regularities, and that the MMN-generating process adjusts a probabilistic model of the environment according to prediction errors.

  6. Recent landmark trials in cardiology.

    PubMed

    Jain, Peeyush; Bhandari, Suman

    2006-01-01

    This section outlines various recent ongoing /completed trials on use of amiodarone, beta blockers, clopidogrel antiplatelet agents, cardiac resynchronization therapy and drug-eluting stents in management of cardiac complications and morbidity.

  7. Effects of the Scopes Trial

    ERIC Educational Resources Information Center

    Grabiner, Judith V.; Miller, Peter D.

    1974-01-01

    Considered are the effects of the Scopes trial on textbook publishers, textbook writers, and textbooks used in schools. The authors question whether it was a victory for evolutionists or for other groups. (RH)

  8. HIV/AIDS Clinical Trials

    MedlinePlus

    ... Contact Us | En Español OFFERING INFORMATION ON HIV/AIDS TREATMENT, PREVENTION, AND RESEARCH Search Search Search Search Search Menu Home Guidelines Understanding HIV/AIDS Drugs Clinical Trials Apps Home Guidelines Understanding HIV/ ...

  9. Clinical trial design in cancer.

    PubMed

    Mould, R F

    1979-07-01

    The design of clinical trials in cancer is a subject which features reasonably often among FRCR (Part 1) examination questions, and as such should be of more than passing interest to oncologists. It is also a subject which is gaining in relevance since the number of trials is increasing annually due in part to the many chemotherapeutic regimes which are being proposed. This paper which is based on a lecture given in Cambridge at the Hospital Physicists' Association Annual Conference in September 1978, is intended to act as an introduction to clinical trial design. References for further reading are given and, in particular, the extensive report on randomised clinical trials to the Medical Research Council's Leukaemia Steering Committee (Peto et al., 1977, 1978) is recommended.

  10. National Lung Screening Trial (NLST)

    Cancer.gov

    The National Lung Screening Trial (NLST), a research study sponsored by the National Cancer Institute that used low-dose helical CT scans or chest X-ray to screen men and women at risk for lung cancer.

  11. Stopping clinical trials by design.

    PubMed

    Whitehead, John

    2004-11-01

    Before any clinical trial begins, a detailed trial protocol must be prepared. The authority of the trial results will depend on the quality of this document. In many protocols, a key component is a plan for a series of interim analyses of the accumulating trial data, and a 'stopping rule' based on them. Such a rule might be intended to prevent participants from continuing to receive a drug that already seems to be unsafe, or to allow a successful drug to become generally available as soon as sufficient evidence of its advantages has been collected. There has been considerable misunderstanding of these rules, and controversies associated with them. Here, I discuss why this might be, and what can be done to promote their successful and beneficial use in the future.

  12. The ALCHEMIST Lung Cancer Trial

    Cancer.gov

    A collection of material about the ALCHEMIST lung cancer trial that will examine tumor tissue from patients with early-stage, completely resected lung cancer for gene mutations in the EGFR and ALK genes, and a

  13. Video on demand internal trial

    NASA Astrophysics Data System (ADS)

    Sell, Chris

    1993-02-01

    This NYNEX internal trial was designed to test a variety of technical concepts pertaining to a true video on demand system. A three building complex was selected for the trial using coaxial and fiber optic transport systems. The trial period was approximately six weeks long with a total of eighteen movies available twenty four hours a day. A fully automated system was designed at the NYNEX Science and Technology Laboratory that incorporated video equipment and laser disk players. This system is controlled by a pair of Sun Microsystems workstations communicating via a local area network. Valuable knowledge was gained in the area of jukebox design, control systems, and menuing. Fiber optic delivery systems were investigated along with coaxial systems. The user base for this trial consisted of NYNEX employees instead of residential customers. Although the user base was not ideal, we gained insight into how people interact with a fully automated system.

  14. Clinical trials in pulmonary hypertension.

    PubMed

    Badesch, D B

    1997-01-01

    Progress in treatment of pulmonary hypertension has been impaired by the lack of formal clinical trials. This is now beginning to change, and the impact on our approach to treating patients with pulmonary hypertension in substantial. As with other relatively uncommon medical disorders, randomized, controlled, multi-center trials are needed to assess the safety and efficacy of potential therapeutic modalities. Treatments showing promise at the level of small pilot studies within a single center should be studied more rigorously.

  15. Recent trials on hemodiafiltration.

    PubMed

    Locatelli, Francesco; Manzoni, Celestina; Del Vecchio, Lucia; Cavalli, Andrea; Pontoriero, Giuseppe

    2011-01-01

    The theoretical advantages of high-flux hemodialysis (HD) in treating patients with chronic kidney disease (CKD) stage 5 are related to the higher toxin removal (especially 'middle molecules'), including sodium and water, and to the better biocompatibility of the treatment, including membrane and water quality. Several observational studies have shown that high-flux HD has positive effects on the survival and morbidity of uremic patients when compared with low-flux HD. The primary analysis of the prospective randomized HEMO (Hemodialysis Outcomes) study showed that high-flux HD was associated with an 8% nonsignificant reduction of mortality in comparison with low-flux HD. However, a secondary analysis pointed to an advantage for high-flux HD in subgroups of patients. More recently, the MPO (Membrane Permeability Outcome) study found that survival could be significantly improved by using high-flux HD compared with low-flux HD in high-risk patients as identified by serum albumin ≤4 g/dl and, in a post hoc analysis, in diabetic patients as a whole. On-line hemodiafiltration (HDF) is considered the most efficient technique of using high-flux membranes. Clearance of small solutes like urea are higher than in hemofiltration, and clearance of middle solutes like β(2)-microglobulin are higher than in high-flux HD. Since there is only a very limited number of randomized prospective trials comparing HDF and high-flux HD, no conclusive data are available about the effect of increased convection of on-line HDF on survival and morbidity of CKD patients. The suggested advantages of HDF must be confirmed by a large randomized controlled study.

  16. Global warming on trial

    SciTech Connect

    Broeker, W.S.

    1992-04-01

    Jim Hansen, a climatologist at NASA's Goddard Space Institute, is convinced that the earth's temperature is rising and places the blame on the buildup of greenhouse gases in the atmosphere. Unconvinced, John Sununu, former White House chief of staff, doubts that the warming will be great enough to produce serious threat and fears that measures to reduce the emissions would throw a wrench into the gears that drive the Unites States' troubled economy. During his three years at the White House, Sununu's view prevailed, and although his role in the debate has diminished, others continue to cast doubt on the reality of global warming. A new lobbying group called the Climate Council has been created to do just this. Burning fossil fuels is not the only problem; a fifth of emissions of carbon dioxide now come from clearing and burning forests. Scientists are also tracking a host of other greenhouse gases that emanate from a variety of human activities; the warming effect of methane, chlorofluorocarbons and nitrous oxide combined equals that of carbon dioxide. Although the current warming from these gases may be difficult to detect against the background noise of natural climate variation, most climatologists are certain that as the gases continue to accumulate, increases in the earth's temperature will become evident even to skeptics. If the reality of global warming were put on trial, each side would have trouble making its case. Jim Hansen's side could not prove beyond a reasonable doubt that carbon dioxide and other greenhouse gases have warmed the planet. But neither could John Sununu's side prove beyond a reasonable doubt that the warming expected from greenhouse gases has not occurred. To see why each side would have difficulty proving its case, this article reviews the arguments that might be presented in such a hearing.

  17. Malaria Diagnostics in Clinical Trials

    PubMed Central

    Murphy, Sean C.; Shott, Joseph P.; Parikh, Sunil; Etter, Paige; Prescott, William R.; Stewart, V. Ann

    2013-01-01

    Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

  18. Malaria diagnostics in clinical trials.

    PubMed

    Murphy, Sean C; Shott, Joseph P; Parikh, Sunil; Etter, Paige; Prescott, William R; Stewart, V Ann

    2013-11-01

    Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests.

  19. Clinical trials of interventional oncology.

    PubMed

    Arai, Yasuaki

    2012-08-01

    Interventional oncology has great potential to be a good treatment modality in the field of oncology, because its procedures are minimally invasive and fairly quick. However, except for a few procedures such as percutaneous radiofrequency ablation and trans-catheter arterial chemo-embolization that have been recognized as standard treatments for hepatocellular carcinoma, most procedures have not been established as the standard treatment modality due to the limited number of clinical trials with compelling evidence. There are several common problems when performing clinical trials of interventional oncology. The first is that the outcomes of clinical trials are greatly influenced by the level of technical skill of the physicians. The second is that equipment and devices vary widely in countries and regions, and they also influence the outcomes. The third is that the methodology of clinical trials for techniques such as interventional oncology has not yet been established. The fourth is the difficulty of setting appropriate endpoints; quality of life is suitable for evaluating interventional oncology in palliative care, but it is not easy to set as the endpoint. The fifth is the difficulty of employing a blinded design, because the procedure cannot be performed without the physician's awareness. Despite such difficult situations, many multi-institutional clinical trials of interventional oncology have been carried out in Japan, with some challenging results. Establishing evidence is critical to making interventional oncology the standard treatment. Interventional radiologists should know the importance of clinical trials, and should move ahead in this direction in a step-by-step manner.

  20. Birth Control in Clinical Trials

    PubMed Central

    Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.

    2015-01-01

    The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398

  1. 32 CFR 935.105 - Trial.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Trial. 935.105 Section 935.105 National Defense... CODE Criminal Actions § 935.105 Trial. (a) If the accused pleads not guilty, he is entitled to a trial... Court considers practicable and necessary to the ends of justice. There is no trial by jury. (b) All...

  2. 32 CFR 935.105 - Trial.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false Trial. 935.105 Section 935.105 National Defense... CODE Criminal Actions § 935.105 Trial. (a) If the accused pleads not guilty, he is entitled to a trial... Court considers practicable and necessary to the ends of justice. There is no trial by jury. (b) All...

  3. 5 CFR 316.304 - Trial period.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Trial period. 316.304 Section 316.304... Term Employment § 316.304 Trial period. (a) The first year of service of a term employee is a trial... completion of the required trial period in the same manner as prescribed by § 315.802 of this chapter. (b...

  4. 32 CFR 935.105 - Trial.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false Trial. 935.105 Section 935.105 National Defense... CODE Criminal Actions § 935.105 Trial. (a) If the accused pleads not guilty, he is entitled to a trial... Court considers practicable and necessary to the ends of justice. There is no trial by jury. (b) All...

  5. 32 CFR 935.105 - Trial.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Trial. 935.105 Section 935.105 National Defense... CODE Criminal Actions § 935.105 Trial. (a) If the accused pleads not guilty, he is entitled to a trial... Court considers practicable and necessary to the ends of justice. There is no trial by jury. (b) All...

  6. 32 CFR 935.105 - Trial.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Trial. 935.105 Section 935.105 National Defense... CODE Criminal Actions § 935.105 Trial. (a) If the accused pleads not guilty, he is entitled to a trial... Court considers practicable and necessary to the ends of justice. There is no trial by jury. (b) All...

  7. 5 CFR 316.304 - Trial period.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Trial period. 316.304 Section 316.304... Term Employment § 316.304 Trial period. (a) The first year of service of a term employee is a trial... completion of the required trial period in the same manner as prescribed by § 315.802 of this chapter. (b...

  8. 5 CFR 316.304 - Trial period.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Trial period. 316.304 Section 316.304... Term Employment § 316.304 Trial period. (a) The first year of service of a term employee is a trial... completion of the required trial period in the same manner as prescribed by § 315.802 of this chapter. (b...

  9. 47 CFR 5.602 - Market trials.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Market trials. 5.602 Section 5.602... Market Trials § 5.602 Market trials. Unless otherwise stated in the instrument of authorization, experimental radio licenses granted for the purpose of market trials pursuant to § 5.3(k) are subject to...

  10. 47 CFR 5.602 - Market trials.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Market trials. 5.602 Section 5.602... Market Trials § 5.602 Market trials. Unless otherwise stated in the instrument of authorization, experimental radio licenses granted for the purpose of market trials pursuant to § 5.3(k) are subject to...

  11. 5 CFR 316.304 - Trial period.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) The agency may terminate a term employee at any time during the trial period. The employee is entitled... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Trial period. 316.304 Section 316.304... Term Employment § 316.304 Trial period. (a) The first year of service of a term employee is a trial...

  12. The state of infectious diseases clinical trials: a systematic review of ClinicalTrials.gov.

    PubMed

    Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L

    2013-01-01

    There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.

  13. Design, analysis, and presentation of crossover trials

    PubMed Central

    Mills, Edward J; Chan, An-Wen; Wu, Ping; Vail, Andy; Guyatt, Gordon H; Altman, Douglas G

    2009-01-01

    Objective Although crossover trials enjoy wide use, standards for analysis and reporting have not been established. We reviewed methodological aspects and quality of reporting in a representative sample of published crossover trials. Methods We searched MEDLINE for December 2000 and identified all randomized crossover trials. We abstracted data independently, in duplicate, on 14 design criteria, 13 analysis criteria, and 14 criteria assessing the data presentation. Results We identified 526 randomized controlled trials, of which 116 were crossover trials. Trials were drug efficacy (48%), pharmacokinetic (28%), and nonpharmacologic (30%). The median sample size was 15 (interquartile range 8–38). Most (72%) trials used 2 treatments and had 2 periods (64%). Few trials reported allocation concealment (17%) or sequence generation (7%). Only 20% of trials reported a sample size calculation and only 31% of these considered pairing of data in the calculation. Carry-over issues were addressed in 29% of trial's methods. Most trials reported and defended a washout period (70%). Almost all trials (93%) tested for treatment effects using paired data and also presented details on by-group results (95%). Only 29% presented CIs or SE so that data could be entered into a meta-analysis. Conclusion Reports of crossover trials frequently omit important methodological issues in design, analysis, and presentation. Guidelines for the conduct and reporting of crossover trials might improve the conduct and reporting of studies using this important trial design. PMID:19405975

  14. Clinical trials. A pending subject.

    PubMed

    Gil-Extremera, B; Jiménez-López, P; Mediavilla-García, J D

    2017-07-31

    Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  15. Canadian aeronautical mobile data trials

    NASA Technical Reports Server (NTRS)

    Pedersen, Allister; Pearson, Andrea

    1993-01-01

    This paper describes a series of aeronautical mobile data trials conducted on small aircraft (helicopters and fixed wing) utilizing a low-speed store-and-forward mobile data service. The paper outlines the user requirements for aeronautical mobile satellite communications. 'Flight following' and improved wide-area dispatch communications were identified as high priority requirements. A 'proof-of-concept' trial in a Cessna Skymaster aircraft is described. This trial identified certain development work as essential to the introduction of commercial service including antenna development, power supply modifications and doppler software modifications. Other improvements were also proposed. The initial aeronautical mobile data service available for pre-operational (Beta) trials is outlined. Pre-operational field trials commenced in October 1992 and consisted of installations on a Gralen Communications Inc. Cessna 177 and an Aerospatiale Astar 350 series light single engine helicopter. The paper concludes with a discussion of desirable near term mobile data service developments, commercial benefits, current safety benefits and potential future applications for improved safety.

  16. Trials with a new molluscicide

    PubMed Central

    Foster, R.; Teesdale, C.; Poulton, G. F.

    1960-01-01

    A description is given of laboratory and field trials with a new molluscicide, Bayer 73. Following successful laboratory trials at one part per million, a river containing much vegetation and many semi-stagnant pools was treated at this dosage, the application resulting in a complete disappearance of snails and eggs for a minimum distance of 3 miles below the point of application. It is suggested however that caution must be exercised in assessing the results of molluscicide treatments as the usual population sampling techniques may have serious defects at low population densities. The malacological field data are supported by chemical analyses. Further trials are planned as there is evidence that the dosage employed was excessive. PMID:20604060

  17. Economic endpoints in clinical trials.

    PubMed

    Cook, John; Drummond, Michael; Heyse, Joseph F

    2004-04-01

    Healthcare decision makers are increasingly requesting information on the cost and cost-effectiveness of new medicines at the time of product launch. In order to provide this information, data on healthcare resource utilization and, in some cases, costs, may be collected in clinical trials. In this paper, we discuss some of the issues statisticians need to address when it is appropriate to include these economic endpoints in the trial. Several design issues are discussed, including the alternative types of and methods for collecting economic endpoint data, sample size and generalizability. Alternative approaches in the analysis of resource utilization, cost and cost-effectiveness are also presented. Finally, several of the analytic approaches are applied to actual data from a clinical trial.

  18. Basic problems in controlled trials.

    PubMed Central

    Burkhardt, R; Kienle, G

    1983-01-01

    On the basis of critical discussions which have taken place in recent years in the Federal Republic of Germany, certain methodological, ethical and legal problems arising in relation to controlled trials are discussed. Because of methodological inconsistencies inherent in the experimental approach, the efficacy of a drug must in any case be judged by physicians. This leads to major ethical and even--at least in Germany--legal problems which impose considerable limits on the feasibility of controlled trials in Germany. Editor's note: This paper is written at the invitation of the journal, following the considerable controversy on the ethics of clinical trials in the European Journal of Clinical Pharmacology (8-11). A critical commentary follows the paper with a short response from the authors and a further response from the commentator. PMID:6876102

  19. Clinical trials on AIDS start.

    PubMed

    A 6-month clinical trial in the Philippines sought to determine the efficacy of coconut oil and of "monolaurin," a coconut oil byproduct, in killing HIV by breaking down its coating. This research is based on the theory that medium-chain fatty acids, like monolaurin, can have this effect on certain viruses. The trial involves 12 women and 3 men in the early stage of HIV infection. 10 patients will take different doses of monolaurin, and 5 will consume coconut oil. It is hypothesized that the regimen will lead to higher CD4 counts and a lower viral load. The trial was almost abandoned because it received only lukewarm approval from the Health Secretary.

  20. Systematic characterization of gastrointestinal clinical trials.

    PubMed

    Espinoza, Magdalena; Hsieh, Antony; Hsiehchen, David

    2016-05-01

    Clinical guidelines are commonly based on inadequate evidence, suggesting deficiencies in the present portfolio of clinical research. To investigate characteristics of clinical trials examining gastrointestinal (GI) diseases registered in ClinicalTrials.gov. A cross-sectional analysis of 13,647 GI trials and 111,535 non-GI trials initiated between January 1997 and September 2013 was performed. Entries were sorted by operational status, purpose, interventions, trial design, and epochs to identify trends and interactions in trial properties. The global production of GI trials has remained static in recent years and a majority of research efforts are focused on a few diseases. While GI trials are generally produced by highly populated US states and countries, they are also seldom larger than 500 patients. The likelihood of using data monitoring committees, randomization, and double blinding in GI trials has increased over time, though a substantial fraction of GI trials still do not employ rigorous trial designs. While levels of GI trials correlate with disease burden, the explained variance of GI trials by disease burden worldwide is poor. GI trials are chiefly concentrated in few diseases and highly populated regions, exhibit heterogeneous trends and methodologies, and are sensitive to disease burdens, though more so within North America than worldwide. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  1. Data collection in pragmatic trials.

    PubMed

    Meinecke, Anna-Katharina; Welsing, Paco; Kafatos, George; Burke, Des; Trelle, Sven; Kubin, Maria; Nachbaur, Gaelle; Egger, Matthias; Zuidgeest, Mira

    2017-07-14

    Pragmatic trials can improve our understanding of how treatments will perform in routine practice. In a series of eight papers, the GetReal Consortium has evaluated the challenges in designing and conducting pragmatic trials and their specific methodological, operational, regulatory, and ethical implications. The present final paper of the series discusses the operational and methodological challenges of data collection in pragmatic trials. A more pragmatic data collection needs to balance the delivery of highly accurate and complete data with minimizing the level of interference that data entry and verification induce with clinical practice. Furthermore, it should allow for the involvement of a representative sample of practices, physicians, and patients who prescribe/receive treatment in routine care. This paper discusses challenges that are related to the different methods of data collection and presents potential solutions where possible. No one-size-fits-all recommendation can be given for the collection of data in pragmatic trials, although in general the application of existing routinely used data-collection systems and processes seems to best suit the pragmatic approach. However, data access and privacy, the time points of data collection, the level of detail in the data, and the lack of a clear understanding of the data-collection process were identified as main challenges for the usage of routinely collected data in pragmatic trials. A first step should be to determine to what extent existing health care databases provide the necessary study data and can accommodate data collection and management. When more elaborate or detailed data collection or more structured follow-up is required, data collection in a pragmatic trial will have to be tailor-made, often using a hybrid approach using a dedicated electronic case report form (eCRF). In this case, the eCRF should be kept as simple as possible to reduce the burden for practitioners and minimize influence on

  2. Achieving consensus for clinical trials

    PubMed Central

    Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, C. Oliver; Walsh, Karin S.; Wolters, Pamela L.; Widemann, Brigitte C.

    2013-01-01

    The neurofibromatoses (NF)—including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis—are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801

  3. Clinical Trials in a Dish

    PubMed Central

    Strauss, David G.; Blinova, Ksenia

    2017-01-01

    Clinical trials ‘in a dish’ involve testing medical therapies for safety or effectiveness in the laboratory with human tissue. This has become possible owing to recent biotechnology advances including induced pluripotent stem cells, organs-on-a-chip, and whole-genome sequencing. We provide here an overview of the landscape and highlight steps the FDA is taking to advance the science of clinical trials in a dish and to support the development and validation of new regulatory paradigms to assess drug safety using these new technologies. PMID:27876286

  4. [Reading a clinical trial report].

    PubMed

    Bergmann, J F; Chassany, O

    2000-04-15

    To improve medical knowledge by reading clinical trial reports it is necessary to check for the respect of the methodological rules, and to analyze and criticize the results. A control group and a randomisation are always necessary. Double blind assessment, sample size calculation, intention to treat analysis, a unique primary end point are also important. The conclusions of the trial are valid only for the population included and the clinical signification of the results, depending on the control treatment, has to be evaluated. Respect of the reading rules is necessary to assess the reliability of the conclusions, in order to promote evidence-based practice.

  5. [Trial of analgesia by acupuncture].

    PubMed

    Leger, L; Lande, M; Lepoivre, M

    The clinical trial involved 31 cases, 10 in stomatology. Acupuncture may produce analgesia after simple premedication. Of 21 abdominal operations, in 5 completion of effect using local infiltration of a few millilitres of lignocaine or intravenous pentazocine was required. In 7, general anaesthesia was required to complete the operation. All patients not receiving supplementary general anaesthesia were able to eat normally as soon as they were back in bed, passed flactus the same day and had a bowel movement the next day. Ten stomatological operations may be considered to be successful. Further pursual of these trials is justified.

  6. Trials by Juries: Suggested Practices for Database Trials

    ERIC Educational Resources Information Center

    Ritterbush, Jon

    2012-01-01

    Librarians frequently utilize product trials to assess the content and usability of a database prior to committing funds to a new subscription or purchase. At the 2012 Electronic Resources and Libraries Conference in Austin, Texas, three librarians presented a panel discussion on their institutions' policies and practices regarding database…

  7. Trials by Juries: Suggested Practices for Database Trials

    ERIC Educational Resources Information Center

    Ritterbush, Jon

    2012-01-01

    Librarians frequently utilize product trials to assess the content and usability of a database prior to committing funds to a new subscription or purchase. At the 2012 Electronic Resources and Libraries Conference in Austin, Texas, three librarians presented a panel discussion on their institutions' policies and practices regarding database…

  8. 37 CFR 42.4 - Notice of trial.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Notice of trial. 42.4 Section... COMMERCE TRIAL PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Trial Practice and Procedure General § 42.4 Notice of trial. (a) Institution of trial. The Board institutes the trial on behalf of the...

  9. 37 CFR 42.4 - Notice of trial.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Notice of trial. 42.4 Section... COMMERCE TRIAL PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Trial Practice and Procedure General § 42.4 Notice of trial. (a) Institution of trial. The Board institutes the trial on behalf of the...

  10. Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov.

    PubMed

    Lebensburger, Jeffrey D; Hilliard, Lee M; Pair, Lauren E; Oster, Robert; Howard, Thomas H; Cutter, Gary R

    2015-12-01

    The registry ClinicalTrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials. To understand the state of sickle cell disease clinical trials, a comprehensive review of all 174 "closed," "interventional" sickle cell trials registered at ClinicalTrials.gov was completed in January 2015. The majority of registered sickle cell disease clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for sickle cell disease trials focused on pain (23%), bone marrow transplant (BMT) (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). A total of 52 trials were listed as terminated or withdrawn, including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the ClinicalTrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in ClinicalTrials.gov, four acknowledged failure to enroll participants as a reason for trial termination or withdrawal, and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript. ClinicalTrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of sickle cell disease trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results. © The Author(s) 2015.

  11. Clinical Trials in Your Community

    Cancer.gov

    The NCI Community Oncology Research Program (NCORP) is a national network of investigators, cancer care providers, academic institutions, and other organizations. NCORP conducts multi-site cancer clinical trials and studies in diverse populations in community-based healthcare systems across the United States and Puerto Rico.

  12. Sarcopenia: designing phase IIB trials.

    PubMed

    Chumlea, Wm C; Cesari, M; Evans, W J; Ferrucci, L; Fielding, R A; Pahor, M; Studenski, S; Vellas, B

    2011-06-01

    Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x-ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength.

  13. The Trials of Presidential Impeachment.

    ERIC Educational Resources Information Center

    Finkelman, Paul

    1999-01-01

    Compares the impeachment proceedings in the trials of Andrew Johnson, Richard Nixon, and Bill Clinton. Categorizes an impeachable offense as one that threatens the safety of the country, either as treason or bribery. Asserts that President Clinton did not violate the Constitution and therefore should not have been impeached. (CMK)

  14. Fresno County Mock Trial Competition.

    ERIC Educational Resources Information Center

    Fresno City Unified School District, CA.

    THE FOLLOWING IS THE FULL TEXT OF THIS DOCUMENT: The Fresno County Office of Education and the Fresno Unified School District hosted the Mock Trial Competition. The state competition is sponsored by the Constitutional Rights Foundation, with cosponsorship from the California State Bar Association and the California Young Lawyer's Association. This…

  15. Evaluation Using Sequential Trials Methods.

    ERIC Educational Resources Information Center

    Cohen, Mark E.; Ralls, Stephen A.

    1986-01-01

    Although dental school faculty as well as practitioners are interested in evaluating products and procedures used in clinical practice, research design and statistical analysis can sometimes pose problems. Sequential trials methods provide an analytical structure that is both easy to use and statistically valid. (Author/MLW)

  16. Mock Trials and Critical Thinking.

    ERIC Educational Resources Information Center

    Karraker, Meg Wilkes

    1993-01-01

    One college teacher's use of mock trials in sociology instruction is described. Students are assigned roles as petitioner, respondent, attorneys, judge, courtroom staff, witnesses, reporters, and jurors. Pretrial investigations provide experience in information-gathering and critical thinking. Posttrial debriefing reveals others' thinking…

  17. Clinical trials for predictive medicine.

    PubMed

    Simon, Richard

    2012-11-10

    Developments in biotechnology and genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians. The ability to molecularly characterize human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials. In oncology, treatment of broad populations with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine. We review prospective designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single candidate biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are Phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier. We have outlined a prediction-based approach to the analysis of randomized clinical trials that both preserves the Type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen.

  18. SARCOPENIA: DESIGNING PHASE IIB TRIALS

    PubMed Central

    CHUMLEA, WM.C.; CESARI, M.; EVANS, W.J.; FERRUCCI, L.; FIELDING, R.A.; PAHOR, M.; STUDENSKI, S.; VELLAS, B.

    2012-01-01

    Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength. PMID:21623466

  19. Trials with a Strain Gauge.

    ERIC Educational Resources Information Center

    Auty, Geoff

    1996-01-01

    Describes an attempt to match the goals of the practical demonstration of the use of a strain gauge and the technical applications of science and responding to student questions in early trials, while keeping within the level of electronics in advanced physics. (Author/JRH)

  20. Pragmatic trial design elements showed a different impact on trial interpretation and feasibility than explanatory elements.

    PubMed

    Nieuwenhuis, Joost B; Irving, Elaine; Oude Rengerink, Katrien; Lloyd, Emily; Goetz, Iris; Grobbee, Diederick E; Stolk, Pieter; Groenwold, Rolf H H; Zuidgeest, Mira G P

    2016-09-01

    To illustrate how pragmatic trial design elements or inserting explanatory trial elements in pragmatic trials affect validity, generalizability, precision, and operational feasibility. From illustrative examples identified through the IMI Get Real Consortium, we selected randomized drug trials with a pragmatic design feature. We searched all publications on these trials for information on how pragmatic trial design features affect validity, generalizability, precision, or feasibility. We present examples from the Salford lung study, International Suicide Prevention Trial, Sequenced Treatment Alternatives to Relieve Depression, and Cluster Randomized Usual care vs. Caduet Investigation Assessing Long-term-risk trial. These examples show that incorporating pragmatic trial design elements in trials may affect generalizability, precision and validity and may lead to operational challenges different from traditional explanatory trials. Inserting explanatory trial elements into pragmatic trials may also affect validity, generalizability, and operational feasibility, especially when these trial elements are incorporated in one arm of the trial only. Design choices that positively affect one of these domains (e.g., generalizability) may negatively affect others (e.g., feasibility). Consequences of incorporating pragmatic or explanatory trial design elements in pragmatic trials should be explicitly considered and balanced for all relevant domains, including validity, generalizability, precision, and operational feasibility. Tools are needed to make these consequences more transparent. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. [Phase I cancer trials methodology].

    PubMed

    Le Tourneau, Christophe; Faivre, Sandrine; Raymond, Eric; Diéras, Véronique

    2007-11-01

    The main objective of phase I cancer trials is to determine precisely the recommended dose of an anticancer agent as a single agent or in a context of combinations of anticancer agents (including cytotoxic agents, immunotherapy, radiotherapy...), that is administered for the first time in man, to further proceed clinical development with phase II and III trials. The recommended dose must have the greatest efficiency with acceptable toxicity. For the anticancer agents, the ratio risk/benefit is high, since toxicities associated with many cancer therapeutic agents are substantial and because the efficacy is often limited. Thus, phase I cancer trials present unique challenges in comparison to other therapeutic areas. Indeed, it is essential to minimize the numbers of patients treated at subefficient dose levels, and in the same time not to expose the patients to unacceptable toxicity. Historically, the first method that has been used is the Fibonacci escalation. The major problems raised with this method have been the lengths of the trials and the risk to treat substantial numbers of patients at nontherapeutix doses. Thus, novel methods have been then developed modifying the numbers of patients included at each dose level and the rapidity of dose escalation. These methods include pharmacologically guided dose escalation, escalation with overdose control and the continual reassessment method which are both statistically based dose escalation methods, and the accelerated titration designs. Concerning the targeted anticancer therapies, the therapeutic effect on the target, due to their higher specificity, can be obtained using doses that have few toxicity. Using the toxicity to determine the recommended dose for phase II trials, as it is the case for "classical > anticancer agents, does not seem to be sufficient. Alternatives to determine the optimal biological dose include measurement of target inhibition, pharmacokinetic analysis and functional imaging.

  2. New Eczema Drug Promising in Early Trial

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163883.html New Eczema Drug Promising in Early Trial Nemolizumab significantly ... the appearance of moderate to severe eczema, a new, preliminary trial finds. Nemolizumab is a man-made, ...

  3. Adaptive clinical trial designs in oncology

    PubMed Central

    Zang, Yong; Lee, J. Jack

    2015-01-01

    Adaptive designs have become popular in clinical trial and drug development. Unlike traditional trial designs, adaptive designs use accumulating data to modify the ongoing trial without undermining the integrity and validity of the trial. As a result, adaptive designs provide a flexible and effective way to conduct clinical trials. The designs have potential advantages of improving the study power, reducing sample size and total cost, treating more patients with more effective treatments, identifying efficacious drugs for specific subgroups of patients based on their biomarker profiles, and shortening the time for drug development. In this article, we review adaptive designs commonly used in clinical trials and investigate several aspects of the designs, including the dose-finding scheme, interim analysis, adaptive randomization, biomarker-guided randomization, and seamless designs. For illustration, we provide examples of real trials conducted with adaptive designs. We also discuss practical issues from the perspective of using adaptive designs in oncology trials. PMID:25811018

  4. Clinical Trials.Gov: A Topical Analyses.

    PubMed

    Anand, Vibha; Cahan, Amos; Ghosh, Soumya

    2017-01-01

    ClinicalTrials.gov was established as a web-based registry for clinical trials of human participants in 2000. Mandatory registration started in 2008. Given more than a decade of registered trials, it's important to understand the "topic" areas and their evolution over time from this resource. This information may help in identifying current knowledge gaps. We use dynamic topic model (DTM) methods to discover topics and their evolution over last 17 years. Our model suggests that there are disease or organ specific trials such as 'Cardiovascular disorders', Heart & Brain conditions', or 'Breast & Prostate cancer' as well as trials registered for general health. General health trials are less likely to be FDA regulated, but both health and pain management, as well as surgical, heart, and brain trials have upward trend in recent years while advanced cancer trials have downward trended. Our model derives unique insights from metadata associated with each topic area.

  5. A pragmatic view on pragmatic trials

    PubMed Central

    Patsopoulos, Nikolaos A.

    2011-01-01

    Clinical trials have been the main tool used by the health sciences community to test and evaluate interventions. Trials can fall into two broad categories: pragmatic and explanatory. Pragmatic trials are designed to evaluate the effectiveness of interventions in real-life routine practice conditions, whereas explanatory trials aim to test whether an intervention works under optimal situations. Pragmatic trials produce results that can be generalized and applied in routine practice settings. Since most results from exploratory trials fail to be broadly generalizable, the “pragmatic design” has gained momentum. This review describes the concept of pragmatism, and explains in particular that there is a continuum between pragmatic and explanatory trials, rather than a dichotomy. Special focus is put on the limitations of the pragmatic trials, while recognizing the importance for and impact of this design on medical practice. PMID:21842619

  6. Spine device clinical trials: design and sponsorship.

    PubMed

    Cher, Daniel J; Capobianco, Robyn A

    2015-05-01

    Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 32 CFR 935.111 - New trial.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false New trial. 935.111 Section 935.111 National... WAKE ISLAND CODE Appeals and New Trials § 935.111 New trial. A Judge of the Wake Island Court may order a new trial as required in the interest of justice, or vacate any judgment and enter a new one, on...

  8. Hyperbaric Oxygenation (HBO) Clinical Trials: A Review

    DTIC Science & Technology

    1990-05-01

    16 Table 3. HBO Clinical Trials: Multiple Sclerosis ..... 17 Table 4. HBO Clinical Trials: Diabetic Foot Ulcers.. .17 Table 5. HBO...treatment of multiple sclerosis (MS) (table 3), and two reported on diabetic foot ulcers (table 4). The remaining seven reported on seven different...group of MS trials is convincing that HBO was not effective for MS. The diabetic foot ulcer trials are difficult to compare. They used different HBO

  9. 32 CFR 935.111 - New trial.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false New trial. 935.111 Section 935.111 National... WAKE ISLAND CODE Appeals and New Trials § 935.111 New trial. A Judge of the Wake Island Court may order a new trial as required in the interest of justice, or vacate any judgment and enter a new one, on...

  10. 32 CFR 935.111 - New trial.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false New trial. 935.111 Section 935.111 National... WAKE ISLAND CODE Appeals and New Trials § 935.111 New trial. A Judge of the Wake Island Court may order a new trial as required in the interest of justice, or vacate any judgment and enter a new one, on...

  11. 32 CFR 935.111 - New trial.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false New trial. 935.111 Section 935.111 National... WAKE ISLAND CODE Appeals and New Trials § 935.111 New trial. A Judge of the Wake Island Court may order a new trial as required in the interest of justice, or vacate any judgment and enter a new one, on...

  12. 32 CFR 935.111 - New trial.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false New trial. 935.111 Section 935.111 National... WAKE ISLAND CODE Appeals and New Trials § 935.111 New trial. A Judge of the Wake Island Court may order a new trial as required in the interest of justice, or vacate any judgment and enter a new one, on...

  13. The Design of Cluster Randomized Crossover Trials

    ERIC Educational Resources Information Center

    Rietbergen, Charlotte; Moerbeek, Mirjam

    2011-01-01

    The inefficiency induced by between-cluster variation in cluster randomized (CR) trials can be reduced by implementing a crossover (CO) design. In a simple CO trial, each subject receives each treatment in random order. A powerful characteristic of this design is that each subject serves as its own control. In a CR CO trial, clusters of subjects…

  14. The Scopes Trial: A Mini-Unit.

    ERIC Educational Resources Information Center

    DeWitt, Scott W.

    1999-01-01

    Asks secondary students to compare the real Scopes trial to the fictionalized version presented in the movie "Inherit the Wind," with their textbook and Web site versions. Intends for students to learn about key facts, arguments, and outcomes of the trial and to understand significant individuals' impacts on the trial's events and…

  15. The Scopes Trial: A Mini-Unit.

    ERIC Educational Resources Information Center

    DeWitt, Scott W.

    1999-01-01

    Asks secondary students to compare the real Scopes trial to the fictionalized version presented in the movie "Inherit the Wind," with their textbook and Web site versions. Intends for students to learn about key facts, arguments, and outcomes of the trial and to understand significant individuals' impacts on the trial's events and…

  16. Clinical Trials Management | Division of Cancer Prevention

    Cancer.gov

    Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials.

  17. 50 CFR 27.91 - Field trials.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Field trials. 27.91 Section 27.91 Wildlife... NATIONAL WILDLIFE REFUGE SYSTEM PROHIBITED ACTS Other Disturbing Violations § 27.91 Field trials. The conducting or operation of field trials for dogs on national wildlife refuges is prohibited except as may...

  18. 50 CFR 27.91 - Field trials.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Field trials. 27.91 Section 27.91 Wildlife... NATIONAL WILDLIFE REFUGE SYSTEM PROHIBITED ACTS Other Disturbing Violations § 27.91 Field trials. The conducting or operation of field trials for dogs on national wildlife refuges is prohibited except as may...

  19. 50 CFR 27.91 - Field trials.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Field trials. 27.91 Section 27.91 Wildlife... NATIONAL WILDLIFE REFUGE SYSTEM PROHIBITED ACTS Other Disturbing Violations § 27.91 Field trials. The conducting or operation of field trials for dogs on national wildlife refuges is prohibited except as may...

  20. 50 CFR 27.91 - Field trials.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Field trials. 27.91 Section 27.91 Wildlife... NATIONAL WILDLIFE REFUGE SYSTEM PROHIBITED ACTS Other Disturbing Violations § 27.91 Field trials. The conducting or operation of field trials for dogs on national wildlife refuges is prohibited except as may...

  1. Nurses' unique roles in randomized clinical trials.

    PubMed

    Sadler, G R; Lantz, J M; Fullerton, J T; Dault, Y

    1999-01-01

    Nurses are in an ideal position to promote patients' awareness of the role played by clinical trials in the advancement of health science and the subsequent improvement of patient care. The history of clinical trials and the four phases of clinical trials are described. Nurses' professional roles in clinical trial participation, such as helping the patient to identify open clinical trials and acting as clinical interpreter and patient advocate during the patient's participation in a trial, are detailed. Professional considerations that must be addressed by the nurse are reviewed and include ensuring that the trial has received approval from an Institutional Review Board for the participation of human subjects; that the responsibilities of participation are congruent with the nurse's personal values and workplace obligations; and that once engaged, the nurse can make the commitment to sustain participation in the trial. Most important, the nurse must keep the patient's needs and values uppermost in mind during the evaluation of potential clinical trials. Nurses have a critical role to play in the promotion of clinical trials, the recruitment of patients for clinical trial participation, the education of the patient and family, and the clinical care and support of patients throughout their participation in clinical trials.

  2. Potential bias in ophthalmic pharmaceutical clinical trials

    PubMed Central

    Varner, Paul

    2008-01-01

    To make clinicians aware of potential sources of error in ophthalmic pharmaceutical clinical trials that can lead to erroneous interpretation of results, a critical review of the study design of various pharmaceutical ophthalmic clinical trials was completed. Discrepancies as a result of study shortcomings may explain observed differences between reported ophthalmic trial data and observed clinical results. PMID:19668731

  3. Varied acceptance of clinical trial results.

    PubMed

    Klimt, C R

    1989-12-01

    The subject of varied acceptance of clinical trial results is discussed in the context of review of trials with which I have been involved and my subjective evaluation of their impact on the practice of clinical medicine. My experience goes back to 1949 and a World Health Organization trial of hyperimmune gamma globulin against rabies. This was followed by a large trial of secondary prevention of poliomyelitis. I participated in the planning and initiation of the first chronic disease trial, the University Group Diabetes Program (UGDP). The latter lasted for 15 years and its ramifications continue to this day. My next trial was the Coronary Drug Project (CDP), a complex trial with more than 8,000 patients. The trials of aspirin and aspirin combined with persantine (the CDPA, AMIS, PARIS I, and PARIS II) followed. My last three trials were a trial of photocoagulation in diabetic retinopathy (DRS), a six-country trial of the antiarrhythmic drug mexiletine (IMPACT), and a study involving two diagnostic procedures for pulmonary embolism (PIOPED). When one considers, in retrospect, the plethora of trials one is struck by the uniform absence of a priori considerations of the impact on medical practice, or likely lack thereof, of possible outcomes.

  4. The Design of Cluster Randomized Crossover Trials

    ERIC Educational Resources Information Center

    Rietbergen, Charlotte; Moerbeek, Mirjam

    2011-01-01

    The inefficiency induced by between-cluster variation in cluster randomized (CR) trials can be reduced by implementing a crossover (CO) design. In a simple CO trial, each subject receives each treatment in random order. A powerful characteristic of this design is that each subject serves as its own control. In a CR CO trial, clusters of subjects…

  5. Teachable Trials in the Social Studies Classroom

    ERIC Educational Resources Information Center

    Weiner, Mark S.

    2010-01-01

    At the heart of the Western intellectual tradition, particularly the value it places on the critical analysis of civic life, or social studies, lies the story of a trial. If the story of a trial lies at the root of social studies, then it comes as no surprise that many teachers find that trials can serve as excellent teaching tools, especially for…

  6. The Internet and randomised controlled trials.

    PubMed

    Kelly, M A; Oldham, J

    1997-11-01

    Several factors constrain the implementation of Randomised Controlled Trials (RCTs). To obtain large sample sizes a multicentred multinational trial may be necessary or a long sampling period. The larger the trial the larger is the unit cost. To allow larger sample sizes, shorter sampling periods and lower unit costs, new methods are needed. The Internet and in particular the WWW provides such an opportunity. The WWW can provide global access, fast interaction and automation. A prototype Internet Trials Service (ITS) is currently being tested with a real international clinical trial (the Growth Restriction Intervention Trial--GRIT). The ITS is hosted on a Web server. It provides a series of HTML documents that describe the GRIT protocol. Registered centres may enter patients into the GRIT trial via ITS. Java applets are used to collect trial data before returning the study number and randomisation. ITS assumes all trial data will be intercepted by a sniffer. Therefore no information is sent that could specifically identify a patient, this must be sent later by more secure means. ITS assumes that trial centres can be spoofed. To authenticate the patients entered into the trial and the trial data sent, a regular audit report is sent to each centre by secure means for confirmation. By using Java, a full functional data entry system can be developed that runs locally within any Java enabled browser. It can perform data validation locally and also provide a sophisticated user interface.

  7. Enhancing Adherence in Clinical Exercise Trials.

    ERIC Educational Resources Information Center

    O'Neal, Heather A.; Blair, Steven N.

    2001-01-01

    Discusses exercise adherence from the perspective of adhering to an exercise treatment in a controlled trial, focusing on: adherence (to intervention and measurement); the development of randomized clinical trials; exemplary randomized clinical trials in exercise science (exercise training studies and physical activity interventions); and study…

  8. 5 CFR 316.304 - Trial period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS TEMPORARY AND TERM EMPLOYMENT Term Employment § 316.304 Trial period. (a) The first year of service of a term employee is a trial...) The agency may terminate a term employee at any time during the trial period. The employee is...

  9. Trial-to-Trial Fluctuations in Attentional State and Their Relation to Intelligence

    ERIC Educational Resources Information Center

    Unsworth, Nash; McMillan, Brittany D.

    2014-01-01

    Trial-to-trial fluctuations in attentional state while performing measures of intelligence were examined in the current study. Participants performed various measures of fluid and crystallized intelligence while also providing attentional state ratings prior to each trial. It was found that pre-trial attentional state ratings strongly predicted…

  10. Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

    PubMed

    Kurbel, Sven; Mihaljević, Slobodan

    2017-10-01

    Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. © 2017 WILEY Periodicals, Inc.

  11. [Practice and thought for quality control of drug clinical trial institution for clinical trials].

    PubMed

    Zhao, Ting; Wu, Ping; Li, Yong; Lian, Feng-mei; Liu, Ping; Qiao, Jie

    2014-12-01

    The quality control of new drug cilnical trial is the effective guaranty for the pharmaceutical safety and effective after available on market. Enhancing the inspection and quality control of new drug clinical trials provide the crucial importance to achieve a persistent profitable standard. This paper mainly discussed the problems of current clinical trials based on annual check of drug clinical trial institution.

  12. Trial-to-Trial Fluctuations in Attentional State and Their Relation to Intelligence

    ERIC Educational Resources Information Center

    Unsworth, Nash; McMillan, Brittany D.

    2014-01-01

    Trial-to-trial fluctuations in attentional state while performing measures of intelligence were examined in the current study. Participants performed various measures of fluid and crystallized intelligence while also providing attentional state ratings prior to each trial. It was found that pre-trial attentional state ratings strongly predicted…

  13. Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov.

    PubMed

    Cihoric, Nikola; Tsikkinis, Alexandros; Minniti, Giuseppe; Lagerwaard, Frank J; Herrlinger, Ulrich; Mathier, Etienne; Soldatovic, Ivan; Jeremic, Branislav; Ghadjar, Pirus; Elicin, Olgun; Lössl, Kristina; Aebersold, Daniel M; Belka, Claus; Herrmann, Evelyn; Niyazi, Maximilian

    2017-01-03

    The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

  14. The ethics of clinical trials

    PubMed Central

    Nardini, Cecilia

    2014-01-01

    Over the past decades, randomised controlled trials (RCTs) have prevailed over clinical judgement, case reports, and observational studies and became the gold evidential standard in medicine. Furthermore, during the same time frame, RCTs became a crucial part of the regulatory process whereby a new therapeutic can gain access to the drug market. Today, clinical trials are large and tightly regulated enterprises that have to comply with ethical requirements while maintaining high epistemic standards, a balance that becomes increasingly difficult as the research questions become more sophisticated. In this review, the author will discuss some of the most important ethical issues surrounding RCTs, with an eye to the most recent debates and the context of oncological research in particular. PMID:24482672

  15. Medical coding in clinical trials.

    PubMed

    Babre, Deven

    2010-01-01

    Data generated in all clinical trial are recorded on the data collection instrument Case report Form / Electronic Case Report Form by investigators located at various sites in various countries. In multicentric clinical trials since different investigator or medically qualified experts are from different sites / centers recording the medical term(s) uniformly is a big challenge. Medical coders from clinical data management team process these terms and perform medical coding. Medical coding is performed to categorize the medical terms reported appropriately so that they can be analyzed/reviewed. This article describes process which is used for medical coding in clinical data management and two most commonly used medical dictionaries MedDRA and WHO-DDE in brief. It is expected to help medical coders to understand the process of medical coding in clinical data management. Few common issues which the medical coder faces while performing medical coding, are also highlighted.

  16. Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution.

    PubMed

    Luce, Bryan R; Connor, Jason T; Broglio, Kristine R; Mullins, C Daniel; Ishak, K Jack; Saunders, Elijah; Davis, Barry R

    2016-09-20

    Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs. To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research. Virtual execution of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design. Comparative effectiveness trial of antihypertensive medications. Patient data sampled from the more than 42 000 patients enrolled in ALLHAT with publicly available data. Number of patients randomly assigned between groups, trial duration, observed numbers of events, and overall trial results and conclusions. The Bayesian adaptive approach and original design yielded similar overall trial conclusions. The Bayesian adaptive trial randomly assigned more patients to the better-performing group and would probably have ended slightly earlier. This virtual trial execution required limited resampling of ALLHAT patients for inclusion in RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials). Involvement of a data monitoring committee and other trial logistics were not considered. In a comparative effectiveness research trial, Bayesian adaptive trial designs are a feasible approach and potentially generate earlier results and allocate more patients to better-performing groups. National Heart, Lung, and Blood Institute.

  17. Clinical Trials in Head Injury

    PubMed Central

    NARAYAN, RAJ K.; MICHEL, MARY ELLEN; Ansell, Beth; Baethmann, Alex; Biegon, Anat; Bracken, Michael B.; Bullock, M. Ross; Choi, Sung C.; Clifton, Guy L.; Contant, Charles F.; Coplin, William M.; Dietrich, W. Dalton; Ghajar, Jamshid; Grady, Sean M.; Grossman, Robert G.; Hall, Edward D.; Heetderks, William; Hovda, David A.; Jallo, Jack; Katz, Russell L.; Knoller, Nachshon; Kochanek, Patrick M.; Maas, Andrew I.; Majde, Jeannine; Marion, Donald W.; Marmarou, Anthony; Marshall, Lawrence F.; McIntosh, Tracy K.; Miller, Emmy; Mohberg, Noel; Muizelaar, J. Paul; Pitts, Lawrence H.; Quinn, Peter; Riesenfeld, Gad; Robertson, Claudia S.; Strauss, Kenneth I.; Teasdale, Graham; Temkin, Nancy; Tuma, Ronald; Wade, Charles; Walker, Michael D.; Weinrich, Michael; Whyte, John; Wilberger, Jack; Young, A. Byron; Yurkewicz, Lorraine

    2006-01-01

    Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research. PMID:12042091

  18. Clinical Trials in Noninfectious Uveitis

    PubMed Central

    Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

    2015-01-01

    The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763

  19. Medical marijuana: tribulations and trials.

    PubMed

    Abrams, D I

    1998-01-01

    Widespread use of smoked marijuana in the San Francisco Bay Area as a treatment for HIV-related anorexia and weight loss, as well as nausea related to prescribed therapy, prompted the design of a clinical trial to evaluate the safety and effectiveness of this controlled substance. The Community Consortium--the Bay Area's community-based HIV clinical trials organization--designed a first pilot evaluation of smoked marijuana compared to oral tetrahydrocannabinol (THC, synthesized as dronabinol or Marinol) in 1993. A legal source of marijuana could not be identified. Two subsequent applications to the National Institutes of Health were submitted in 1996 and 1997. During the intervening period, increasing numbers of people with HIV infection were obtaining marijuana for "medicinal use" from local Cannabis Buyer's Clubs. In November 1996, California voters endorsed the medical use of marijuana by approving Proposition 215. The federal government's attempt to oppose the voters' mandate led to public outrage. Organized medicine demanded more studies into marijuana's potential use as medicine. The consortium's 1997 proposal to evaluate the potential interaction between THC and widely-prescribed protease inhibitors was positively received. Funding and study-required marijuana cigarettes have been obtained from the National Institute of Drug Abuse, and the first subjects are being enrolled in the trial. When politically sensitive research proposals include sound science, they can prevail if investigators are willing to persist.

  20. Terrain commander UGS operational trials

    NASA Astrophysics Data System (ADS)

    Steadman, Robert L.

    2004-09-01

    Operational trials of Textron Systems" Terrain Commander unattended ground sensor (UGS) system are described. Terrain Commander is a powerful new concept in surveillance and remote situational awareness. It leverages a diverse suite of sophisticated unattended ground sensors, day/night electro-optics, satellite data communications, and an advanced Windows based graphic user interface. Terrain Commander OASIS (Optical Acoustic SATCOM Integrated Sensor) provides next generation target detection, classification, and tracking through smart sensor fusion of beam-forming acoustic, seismic, passive infrared, and magnetic sensors. With its fully integrated SATCOM system using internet protocols, virtually any site in the world can be monitored from almost any other location. Multiple remote sites such as airfields, landing zones, base perimeters, road junctions, flanks, and border crossings are monitored with ease from a central location. Intruding personnel or vehicles are automatically detected, classified, and imaged. Results from early operational trials in the outback of Australia and in various locations in the US are described. Probability of detection and recognition against a wide variety of targets including personnel, military and civilian vehicles, in-shore watercraft, and low altitude aircraft are discussed. Environments include snow cover, tropical savannah, rainforest, and woodlands. Experience with alternative SATCOM systems during the trials is also touched upon.

  1. Clinical trials and gender medicine.

    PubMed

    Cassese, Mariarita; Zuber, Veronica

    2011-01-01

    Women use more medicines than men because they fall ill more often and suffer more from chronic diseases, but also because women pay more attention to their health and have more consciousness and care about themselves. Although medicines can have different effects on women and men, women still represent a small percentage in the first phases of trials (22%) which are essential to verify drugs dosage, side effects, and safety. Even though women are more present in trials, studies results are not presented with a gender approach. This situation is due to educational, social, ethical and economical factors. The scientific research must increase feminine presence in clinical trials in order to be equal and correct, and all the key stakeholder should be involved in this process. We still have a long way to cover and it doesn't concern only women but also children and old people. The aim is to have a medicine not only illness-focused but patient-focused: a medicine able to take into consideration all the patient characteristics and so to produce a really personalized therapy. What above described is part of the reasons why in 2005 was founded the National Observatory for Women's Health (Osservatorio Nazionale sulla Salute della Donna, ONDa) which promotes a gender health awareness and culture in Italy, at all the levels of the civil and scientific society.

  2. Methodology Series Module 4: Clinical Trials

    PubMed Central

    Setia, Maninder Singh

    2016-01-01

    In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an “open trial.” However, many of the trials are not open – they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184

  3. 37 CFR 42.72 - Termination of trial.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Termination of trial. 42.72... COMMERCE TRIAL PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Trial Practice and Procedure Oral Argument, Decision, and Settlement § 42.72 Termination of trial. The Board may terminate a trial without rendering a...

  4. 37 CFR 42.72 - Termination of trial.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Termination of trial. 42.72... COMMERCE TRIAL PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Trial Practice and Procedure Oral Argument, Decision, and Settlement § 42.72 Termination of trial. The Board may terminate a trial without rendering a...

  5. Credentialing for participation in clinical trials

    PubMed Central

    Followill, David S.; Urie, Marcia; Galvin, James M.; Ulin, Kenneth; Xiao, Ying; FitzGerald, Thomas J.

    2012-01-01

    The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials. PMID:23272300

  6. Outcome reporting among drug trials registered in ClinicalTrials.gov.

    PubMed

    Bourgeois, Florence T; Murthy, Srinivas; Mandl, Kenneth D

    2010-08-03

    Clinical trial registries are in widespread use to promote transparency around trials and their results. To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes. An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006. ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999. Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations. Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials

  7. Data monitoring committees for pragmatic clinical trials.

    PubMed

    Ellenberg, Susan S; Culbertson, Richard; Gillen, Daniel L; Goodman, Steven; Schrandt, Suzanne; Zirkle, Maryan

    2015-10-01

    In any clinical trial, it is essential to monitor the accumulating data to be sure that the trial continues to be safe for participants and that the trial is being conducted properly. Data monitoring committees, independent expert panels who undertake regular reviews of the data as the trial progresses, serve an important role in safeguarding the interests of research participants and ensuring trial integrity in many trials. Many pragmatic clinical trials, which aim to inform healthcare decisions by comparing alternate interventions in heterogeneous healthcare delivery settings, will warrant review by an independent data monitoring committee due to their potential impact on clinical practice. However, the very features that make a trial "pragmatic" may pose challenges in terms of which aspects of a trial to monitor and when it is appropriate for a data monitoring committee to intervene. Using the Pragmatic-Explanatory Continuum Indicator Summary tool that draws distinctions between pragmatic and explanatory clinical trials, we review characteristics of pragmatic clinical trials that may have implications for data monitoring committees and interim monitoring plans. These include broad eligibility criteria, a focus on subjective patient-centered outcomes, and in some cases a lack of standardized follow-up procedures across study sites. Additionally, protocol adherence is often purposefully not addressed in pragmatic trials in order to accurately represent the clinical practice setting and maintain practicability of implementation; there are differing viewpoints as to whether adherence should be assessed and acted upon by data monitoring committees in these trials. Some other issues not specifically related to the Pragmatic-Explanatory Continuum Indicator Summary criteria may also merit special consideration in pragmatic trials. Thresholds for early termination of a pragmatic clinical trial might be controversial. The distinguishing features of pragmatic clinical

  8. Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

    PubMed

    Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

    2012-07-01

    Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

  9. Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.

    PubMed

    Subherwal, Sumeet; Patel, Manesh R; Chiswell, Karen; Tidemann-Miller, Beth A; Jones, W Schuyler; Conte, Michael S; White, Christopher J; Bhatt, Deepak L; Laird, John R; Hiatt, William R; Tasneem, Asba; Califf, Robert M

    2014-11-11

    Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. © 2014 American Heart Association, Inc.

  10. Clinical Trials in Peripheral Vascular Disease: Pipeline and Trial Designs: An Evaluation of the ClinicalTrials.gov Database

    PubMed Central

    Subherwal, Sumeet; Patel, Manesh R.; Chiswell, Karen; Tidemann-Miller, Beth A.; Jones, W. Schuyler; Conte, Michael S.; White, Christopher J.; Bhatt, Deepak L.; Laird, John R.; Hiatt, William R.; Tasneem, Asba; Califf, Robert M.

    2014-01-01

    Background Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); however, until recently it has not been possible to examine the entire clinical trial portfolio of studies for treatment of PVD (both arterial and venous disease). Methods and Results We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower extremity peripheral artery disease and acute stroke (35% and 24%, respectively), while most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients aged >65 years. Enrollment in at least 1 US site decreased from 51% in 2007 to 41% of trials in 2010. Compared with non-cardiology disciplines, PVD trials were more likely to be double-blinded, investigate use of devices and procedures, and have industry sponsorship and assumed funding source, and less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. Conclusions PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. PMID:25239436

  11. Making randomised trials more efficient: report of the first meeting to discuss the Trial Forge platform.

    PubMed

    Treweek, Shaun; Altman, Doug G; Bower, Peter; Campbell, Marion; Chalmers, Iain; Cotton, Seonaidh; Craig, Peter; Crosby, David; Davidson, Peter; Devane, Declan; Duley, Lelia; Dunn, Janet; Elbourne, Diana; Farrell, Barbara; Gamble, Carrol; Gillies, Katie; Hood, Kerry; Lang, Trudie; Littleford, Roberta; Loudon, Kirsty; McDonald, Alison; McPherson, Gladys; Nelson, Annmarie; Norrie, John; Ramsay, Craig; Sandercock, Peter; Shanahan, Daniel R; Summerskill, William; Sydes, Matt; Williamson, Paula; Clarke, Mike

    2015-06-05

    Randomised trials are at the heart of evidence-based healthcare, but the methods and infrastructure for conducting these sometimes complex studies are largely evidence free. Trial Forge ( www.trialforge.org ) is an initiative that aims to increase the evidence base for trial decision making and, in doing so, to improve trial efficiency.This paper summarises a one-day workshop held in Edinburgh on 10 July 2014 to discuss Trial Forge and how to advance this initiative. We first outline the problem of inefficiency in randomised trials and go on to describe Trial Forge. We present participants' views on the processes in the life of a randomised trial that should be covered by Trial Forge.General support existed at the workshop for the Trial Forge approach to increase the evidence base for making randomised trial decisions and for improving trial efficiency. Agreed upon key processes included choosing the right research question; logistical planning for delivery, training of staff, recruitment, and retention; data management and dissemination; and close down. The process of linking to existing initiatives where possible was considered crucial. Trial Forge will not be a guideline or a checklist but a 'go to' website for research on randomised trials methods, with a linked programme of applied methodology research, coupled to an effective evidence-dissemination process. Moreover, it will support an informal network of interested trialists who meet virtually (online) and occasionally in person to build capacity and knowledge in the design and conduct of efficient randomised trials.Some of the resources invested in randomised trials are wasted because of limited evidence upon which to base many aspects of design, conduct, analysis, and reporting of clinical trials. Trial Forge will help to address this lack of evidence.

  12. Characteristics of pediatric cardiovascular clinical trials registered on ClinicalTrials.gov.

    PubMed

    Hill, Kevin D; Chiswell, Karen; Califf, Robert M; Pearson, Gail; Li, Jennifer S

    2014-06-01

    ClinicalTrials.gov is an National Institutes of Health-sponsored registry of federally and privately funded trials. We sought to determine fundamental characteristics of registered pediatric cardiovascular trials (PCVTs). A data set including 68,134 interventional clinical trials was downloaded from ClinicalTrials.gov and entered into a relational database. Aggregate data from PCVTs were compared with other trial specialties. Multivariable logistic regression was used to evaluate factors associated with improved trial quality metrics including blinding and randomization. Between July 1, 2005, and September 27, 2010, 5035 (7%) registered trials targeted pediatric populations, including 213 PCVTs (4.2%), 1,176 pediatric infectious disease trials (23%), 664 pediatric mental health trials (13%), and 346 pediatric hematology/oncology trials (7%). Median (interquartile range) PCVT enrollment was 65 subjects (36-186) and median study duration was 2.3 years (1.3-3.7). The most common PCVTs targeted acquired diseases including hypertension (n = 41, 14%), obesity (n = 26, 9%), pulmonary hypertension (n = 25, 9%), and dyslipidemia (n = 19, 7%). Important factors associated with improved quality metrics included National Institutes of Health as opposed to industry funding (OR, 1.9; P < .0001); trial location (trials with both US and foreign enrollment vs trials with US only or foreign only enrollment, P = .02) and trials restricted to younger children as opposed to trials including adolescents (OR, 1.4; P < .0001). PCVTs represent a small proportion of clinical trials relative to other pediatric subspecialties. Most PCVTs tend to parallel adult morbidities while there is a relative paucity of trials focused on congenital heart disease. These data may be useful to stakeholders in informing decisions regarding the conduct of PCVTs, and to provide insight into mechanisms to advance PCVT infrastructure. Copyright © 2014 Mosby, Inc. All rights reserved.

  13. Factors predicting publication of spinal cord injury trials registered on www.ClinicalTrials. gov.

    PubMed

    DePasse, J Mason; Park, Sara; Eltorai, Adam E M; Daniels, Alan H

    2017-08-11

    Treatment options for spinal cord injuries are currently limited, but multiple clinical trials are underway for a variety of interventions, drugs, and devices. The Food and Drug Administration website www.ClinicalTrials.gov catalogues these trials and includes information on the status of the trial, date of initiation and completion, source of funding, and region. This investigation assesses the factors associated with publication and the publication rate of spinal cord injury trials. Retrospective analysis of publically available data on www.ClinicalTrials.gov. The www.ClinicalTrials.gov was queried for all trials on patients with spinal cord injury, and these trials were assessed for status, type of intervention, source of funding, and region. Multiple literature searches were performed on all completed trials to determine publication status. There were 626 studies identified concerning the treatment of patients with spinal cord injury, of which 250 (39.9%) were completed. Of these, only 119 (47.6%) were published. There was no significant difference in the rate of publication between regions (p> 0.16) or by study type (p> 0.29). However, trials that were funded by the NIH were more likely to be published than trials funded by industry (p= 0.01). The current publication rate of spinal cord injury trials is only 47.6%, though this rate is similar to the publication rate for trials in other fields. NIH-funded trials are significantly more likely to become published than industry-funded trials, which could indicate that some trials remain unpublished due to undesirable results. However, it is also likely that many trials on spinal cord injury yield negative results, as treatments are often ineffective.

  14. [Profile of clinical trials enrolling Brazilian children].

    PubMed

    Vieira, Jean Mendes de Lucena; Lima, Elisangela da Costa; Land, Marcelo Gerardin Poirot; Ventura, Miriam; Coelho, Helena Lutescia Luna

    2017-06-12

    This study aimed to characterize the clinical trials with medicines enrolling Brazilian children and adolescents, registered in the databases of Clinical Trials and the Brazilian Clinical Trials Network (ReBEC) from 1994 to 2014. Only 462 clinical trials enrolled Brazilian children and adolescents. There was an increase in registrations beginning in 2003, with an important drop in 2011. Among these trials, 35.5% were hosted in Brazil. The international clinical trials were mostly conducted by North American companies. In both cases, multinational industry was the principal source of funding. The clinical trials were predominantly phase III with injectable and solid oral pharmaceutical forms of antiviral drugs. Domestic clinical trials showed wider variation in the pharmaceutical forms and higher percentage of liquid formulations, when compared to the international trials. In addition to heavy external dependence for conducting clinical trials, the study emphasized the challenge for pediatric care in Brazil, which presents epidemiological peculiarities in an environment prone to the use of unlicensed medicines for children.

  15. Microbicide clinical trial adherence: insights for introduction

    PubMed Central

    Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabeth; McCormack, Sheena

    2013-01-01

    After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs. PMID:23561044

  16. The Quality of Registration of Clinical Trials

    PubMed Central

    Viergever, Roderik F.; Ghersi, Davina

    2011-01-01

    Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991

  17. Trial Steering Committees in randomised controlled trials: A survey of registered clinical trials units to establish current practice and experiences.

    PubMed

    Conroy, Elizabeth J; Harman, Nicola L; Lane, J Athene; Lewis, Steff C; Murray, Gordon; Norrie, John; Sydes, Matt R; Gamble, Carrol

    2015-12-01

    The Medical Research Council Guidelines for Good Clinical Practice outlines a three-committee trial oversight structure--the day-to-day Trial Management Group, the Data Monitoring Committee and the Trial Steering Committee. In this model, the Trial Steering Committee is the executive committee that oversees the trial and considers the recommendations from the Data Monitoring Committee. There is yet to be in-depth consideration establishing the Trial Steering Committee's role and functionality. A survey to establish Trial Steering Committee's current practices, role and the use and opinion on the Medical Research Council guidelines was undertaken within UK Clinical Research Collaborative registered Clinical Trials Units. Completed surveys were obtained from 38 of 47 fully and partially registered Units. Individual items in the survey were analysed and reported spanning current Trial Steering Committee practices including its role, requirement and experience required for membership; methods to identify members; and meeting frequency. Terms (a document describing the committee's remit, objectives and functionality) were obtained and analysed from 21 of 33 Units with documents in place at their Unit. A total of 20 responders suggested aspects of the current Medical Research Council Guidelines that need improvement. We present the first survey reporting on practices within UK Clinical Research Collaborative registered Clinical Trials Units on the experience and remits of Trial Steering Committees. We have identified a widespread adoption of Medical Research Council Guidelines for Trial Steering Committees in the United Kingdom, but limitations in this existing provision have been identified that need to be addressed. © The Author(s) 2015.

  18. Gatekeepers for pragmatic clinical trials.

    PubMed

    Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven

    2015-10-01

    To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding

  19. Registration of noncommercial randomised clinical trials: the feasibility of using trial registries to monitor the number of trials.

    PubMed

    Raftery, James; Fairbank, Eleanor; Douet, Lisa; Dent, Louise; Price, Alison; Milne, Ruairidh; Walley, Tom

    2012-08-20

    A 2003 survey suggested the number of noncommercial trials in the UK was declining. Formation of the NIHR in 2006 and increased research spending by the Department of Health may have increased the number of noncommercial trials but no data are available. Available data on UK noncommercial trials (were obtained from the two relevant registries: ISRCTN register for the UK, and US ClinicalTrials.gov. Data on each trial were sorted by start year, and compared with the: 2003 survey, and UKCRN portfolio database from 2007. The number of UK noncommercial trials registered rose from 25 in 1990 to 188 in 1999, peaked at 533 in 2003, and fell back to 334 in 2009. Total trials registered was similar to but slightly above those in the 2003 survey up to 1998, then rose sharply to 2002 before falling to 2007. From 2007 to 2009 the number registered to start each year was similar to but slightly above the UKCRN database. Less than 10% of UK noncommercial trials registered with ClinGov for most years before 2005, but this rose to 35% by 2009. For the periods of overlap, trial registration data provide fairly similar totals to other sources on the number of noncommercial trials starting each year. The rise and fall in the number of trials registered between 1999 and 2007 was due to those registered in the ISRCTN database as funded by NHS Trusts. After 2007, the number of trials registered as funded by NHS Trusts has fallen in the ISRCTN register but these trials may have migrated to the US ClinGov register. The total number of noncommercial trial starts, excluding those funded by NHS Trusts, has been upward since around 2002. By 2009 the two main funders were NIHR and charities. Feasibility of using registration data to monitor the number of noncommercial trials has been demonstrated but is complicated by the use of two registers and difficulties in accessing the data. We recommend an annual report on the number of noncommercial trials registering each year.

  20. Juvenile Competency to Stand Trial.

    PubMed

    Stepanyan, Sofia T; Sidhu, Shawn S; Bath, Eraka

    2016-01-01

    Competency to stand trial is interpreted as a protected due process right for all defendants and is defined as a defendant's fundamental knowledge and understanding of the criminal charges being filed, roles and procedures within the courtroom, and a general ability to work with the defense counsel. Questions of competency are most often raised by the judge, defense, or the prosecution, and competency evaluations are most often completed by psychiatrists or psychologists with forensic training or work experience. Mental illness, intellectual disability, developmental disorders, and developmental immaturity are the 4 main factors considered in most juvenile competency evaluations.

  1. Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study.

    PubMed

    Prayle, Andrew P; Hurley, Matthew N; Smyth, Alan R

    2012-01-03

    To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Registry based study of clinical trial summaries. ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Proportion of trials for which results had been reported. The ClinicalTrials.gov registry contained 83,579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ(2) test, P = 2.6 × 10(-9)). Later phase trials were more likely to report results (P = 4.4 × 10(-11)), as were industry funded trials (P = 2.2 × 10(-16)). Most trials subject to mandatory reporting did not report results within a year of completion.

  2. The citation of relevant systematic reviews and randomised trials in published reports of trial protocols.

    PubMed

    Pandis, Nikolaos; Fleming, Padhraig S; Koletsi, Despina; Hopewell, Sally

    2016-12-07

    It is important that planned randomised trials are justified and placed in the context of the available evidence. The SPIRIT guidelines for reporting clinical trial protocols recommend that a recent and relevant systematic review should be included. The aim of this study was to assess the use of the existing evidence in order to justify trial conduct. Protocols of randomised trials published over a 1-month period (December 2015) indexed in PubMed were obtained. Data on trial characteristics relating to location, design, funding, conflict of interest and type of evidence included for trial justification was extracted in duplicate and independently by two investigators. The frequency of citation of previous research including relevant systematic reviews and randomised trials was assessed. Overall, 101 protocols for RCTs were identified. Most proposed trials were parallel-group (n = 74; 73.3%). Reference to an earlier systematic review with additional randomised trials was found in 9.9% (n = 10) of protocols and without additional trials in 30.7% (n = 31), while reference was made to randomised trials in isolation in 21.8% (n = 22). Explicit justification for the proposed randomised trial on the basis of being the first to address the research question was made in 17.8% (n = 18) of protocols. A randomised controlled trial was not cited in 10.9% (95% CI: 5.6, 18.7) (n = 11), while in 8.9% (95% CI: 4.2, 16.2) (n = 9) of the protocols a systematic review was cited but did not inform trial design. A relatively high percentage of protocols of randomised trials involves prior citation of randomised trials, systematic reviews or both. However, improvements are required to ensure that it is explicit that clinical trials are justified and shaped by contemporary best evidence.

  3. Legislation for trial registration and data transparency.

    PubMed

    Bian, Zhao-Xiang; Wu, Tai-Xiang

    2010-05-26

    Public confidence in clinical trials has been eroded by data suppression, misrepresentation and manipulation. Although various attempts have been made to achieve universal trial registration- e.g., Declaration of Helsinki, WHO clinical Trial Registry Platform (WHO ICTRP), the International Committee of Medical Journal Editors requirement- they have not succeeded, probably because they lack the enough power of enforcement.Legislation appears to be the most efficient and effective means to ensure that all researchers register their trials and disseminate their data accurately and in a timely manner. We propose that a global network be established. This could be accomplished in two steps. The first step is to legislate about trial registration and data transparency, such as USA's FDAAA Act 2007; and the second step to establish a global network to ensure uniform, international consistency in policy and enforcement of trial registration and data transparency.

  4. Innovative clinical trial design for pediatric therapeutics

    PubMed Central

    Laughon, Matthew M; Benjamin, Daniel K; Capparelli, Edmund V; Kearns, Gregory L; Berezny, Katherine; Paul, Ian M; Wade, Kelly; Barrett, Jeff; Smith, Phillip Brian; Cohen-Wolkowiez, Michael

    2011-01-01

    Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group. The lack of clinical trials in children is partly due to specific challenges in conducting trials in this patient population. Therapeutics in special populations, including premature infants, obese children and children receiving extracorporeal life support, are even less studied. National research networks in Europe and the USA are beginning to address some of the gaps in pediatric therapeutics using novel clinical trial designs. Recent innovations in pediatric clinical trial design, including sparse and scavenged sampling, population pharmacokinetic analyses and ‘opportunistic’ studies, have addressed some of the historical challenges associated with clinical trials in children. PMID:21980319

  5. The Misguided Ethics of Crossover Trials

    PubMed Central

    Prasad, Vinay; Grady, Christine

    2014-01-01

    Crossover is increasingly favored in trials of cancer therapies; even those that seek to establish the basic efficacy of novel drugs. Crossover is done in part for trial recruitment, but also out of a sense of doing the right thing—offering the investigational agent to more patients. In this paper, we argue that this ethical feeling—that crossover is a preferred trial choice—is misguided. In seeking to sate the desires of participants, we might undermine a trial’s ability to answer a meaningful clinical question. When a trial is incapable of answering a question, it becomes unethical. Using a crossover strategy in oncology clinical trials can make trials less ethical, not more. L’enfer est plein de bonnes volontés et désirs (Hell is full of good wishes and desires)--Saint Bernard of Clairvaux (c.1150) PMID:24365533

  6. "Confirmatory" trials: symptom reduction as efficacy measure.

    PubMed

    James, J S

    1995-08-18

    The problems inherent in confirmatory trials to prove clinical benefit of drugs are discussed and a trial design is proposed which uses symptom reduction, instead of death or AIDS-defining infection, as a primary indicator for determining drug efficacy. The symptom-reduction trial is described, followed by discussions of what this type of trial adds to the markers of HIV disease progression. Arguments against symptom reduction as an outcome measure with counter responses and a summary of advantages of symptom reduction over disease progression in HIV efficacy trials are given. A Food and Drug Administration (FDA) workshop on the design of clinical trials meets on September 6th and 7th, with an advisory committee meeting on September 8th. Interested parties should call Heidi Marchand or Kimberly Miles at (301)443-0104.

  7. Civil society perspectives on negative biomedical HIV prevention trial results and implications for future trials.

    PubMed

    Essack, Zaynab; Koen, Jennifer; Slack, Catherine; Lindegger, Graham; Newman, Peter A

    2012-01-01

    Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building.

  8. Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

    PubMed Central

    Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.

    2014-01-01

    Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255

  9. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

    PubMed

    Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

    2015-05-01

    A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well.

  10. International Clinical Trial Day and clinical trials in Ethiopia and Africa.

    PubMed

    Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed

    2014-12-19

    Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa.

  11. Trial Publication after Registration in ClinicalTrials.Gov: A Cross-Sectional Analysis

    PubMed Central

    Ross, Joseph S.; Mulvey, Gregory K.; Hines, Elizabeth M.; Nissen, Steven E.; Krumholz, Harlan M.

    2009-01-01

    Background ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. Methods and Findings We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Conclusions Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low

  12. Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.

    PubMed

    Ross, Joseph S; Mulvey, Gregory K; Hines, Elizabeth M; Nissen, Steven E; Krumholz, Harlan M

    2009-09-01

    ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements

  13. Gulf War Illness Inflammation Reduction Trial

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-14-1-0477 TITLE: Gulf War Illness Inflammation Reduction Trial PRINCIPAL INVESTIGATOR: Ronald R. Bach, Ph.D...5a. CONTRACT NUMBER Gulf War Illness Inflammation Reduction Trial 5b. GRANT NUMBER W81XWH-14-1-0477 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The objective of this clinical trial is to find an evidence-based treatment for Gulf War Illness

  14. Logistics and management of clinical trials.

    PubMed Central

    Greenberg, G

    1982-01-01

    This chapter is concerned with some of the more mundane aspects of the day to day design, planning, documentation, and management of clinical trials, rather than with the finer points of trial design which are dealt with in detail elsewhere. The points considered here, taken individually, seem obvious and trivial but it is hoped that some may be helpful in obtaining the maximum return for the work invested in running a trial. PMID:7104166

  15. Prudent precaution in clinical trials of nanomedicines.

    PubMed

    Marchant, Gary E; Lindor, Rachel A

    2012-01-01

    Clinical trials of nanotechnology medical products present complex risk management challenges that involve many uncertainties and important risk-risk trade-offs. This paper inquires whether the precautionary principle can help to inform risk management approaches to nanomedicine clinical trials. It concludes that prudent precaution may be appropriate for ensuring the safety of such trials, but that the precautionary principle itself, especially in its more extreme forms, does not provide useful guidance for specific safety measures.

  16. Design of oncology clinical trials: a review.

    PubMed

    Ananthakrishnan, Revathi; Menon, Sandeep

    2013-10-01

    Cancer is a disease that occurs due to the uncontrolled multiplication of cells that invade nearby tissues and can spread to other parts of the body. An increased incidence of cancer in the world has led to an increase in oncology research and in the number of oncology trials. Well designed oncology clinical trials are a key part of developing effective anti-cancer drugs. This review focuses on statistical considerations in the design and analysis of oncology clinical trials.

  17. Antiplatelet agents and randomized trials.

    PubMed

    Diener, Hans-Christoph

    2007-01-01

    Patients who have transient ischemic attack (TIA) or ischemic stroke are at a high risk of having a first or recurrent stroke. The annual risk is between 5% and 15%; the risk is highest in the first 48 hours following a TIA and highest in the first 7 days following an ischemic stroke. Secondary prevention includes antithrombotic therapy, treatment of risk factors, and interventional treatment of carotid stenosis. Antithrombotic options can include antiplatelet drugs such as aspirin, aspirin plus extended-release dipyridamole (ER-DP), clopidogrel, or clopidogrel plus aspirin. Oral anticoagulation is used in patients with a cardiac source of embolism such as atrial fibrillation. Aspirin monotherapy offers a modest risk reduction for recurrent stroke and for the combined endpoint of nonfatal stroke, myocardial infarction (MI), and vascular death. The combination of ER-DP and aspirin was shown to be superior to aspirin monotherapy in several trials. Clopidogrel is superior to aspirin in high-risk patients suffering from stroke, MI, or peripheral arterial disease. The combination of clopidogrel plus aspirin is not superior to aspirin or clopidogrel monotherapy and carries a significantly higher bleeding risk. The combination might offer benefit in short-term secondary prevention after TIA or stroke. Another ongoing trial is currently investigating the possible benefit and side effects of aspirin plus ER-DP versus clopidogrel in secondary stroke prevention.

  18. Supported employment: randomised controlled trial*

    PubMed Central

    Howard, Louise M.; Heslin, Margaret; Leese, Morven; McCrone, Paul; Rice, Christopher; Jarrett, Manuela; Spokes, Terry; Huxley, Peter; Thornicroft, Graham

    2010-01-01

    Background There is evidence from North American trials that supported employment using the individual placement and support (IPS) model is effective in helping individuals with severe mental illness gain competitive employment. There have been few trials in other parts of the world. Aims To investigate the effectiveness and cost-effectiveness of IPS in the UK. Method Individuals with severe mental illness in South London were randomised to IPS or local traditional vocational services (treatment as usual) (ISRCTN96677673). Results Two hundred and nineteen participants were randomised, and 90% assessed 1 year later. There were no significant differences between the treatment as usual and intervention groups in obtaining competitive employment (13% in the intervention group and 7% in controls; risk ratio 1.35, 95% CI 0.95–1.93, P = 0.15), nor in secondary outcomes. Conclusions There was no evidence that IPS was of significant benefit in achieving competitive employment for individuals in South London at 1-year follow-up, which may reflect suboptimal implementation. Implementation of IPS can be challenging in the UK context where IPS is not structurally integrated with mental health services, and economic disincentives may lead to lower levels of motivation in individuals with severe mental illness and psychiatric professionals. PMID:20435968

  19. Antimicrobial Peptides Under Clinical Trials.

    PubMed

    Greber, Katarzyna E; Dawgul, Małgorzata

    2017-01-01

    Today microbial drug resistance has become a serious problem not only within inpatient setting but also within outpatient setting. Repeated intake and unnecessary usage of antibiotics as well as the transfer of resistance genes are the most important factors that make the microorganisms resistant to conventional antibiotics. A large number of antimicrobials successfully used for prophylaxis and therapeutic purposes have now become ineffective [1, 2]. Therefore, new molecules are being studied to be used in the treatment of various diseases. Some of these molecules are structural compounds based on a combination of peptides, for example, naturally occurring endogenous peptide antibiotics and their synthetic analogues or molecules designed de novo using QSAR (quantitative structureproperty relationships)-based methods [3]. Trying to exploit numerous advantages of antimicrobial peptides such as high potency and selectivity, broad range of targets, potentially low toxicity and low accumulation in tissues, pharmaceutical industry aims to develop them as commercially available drugs and appropriate clinical trials are being conducted [4]. In this paper we define clinical trials steps and describe current status of several antimicrobial peptides under clinical development as well as briefly depict peptide drug formulation.

  20. How experimental trial context affects perceptual categorization.

    PubMed

    Palmeri, Thomas J; Mack, Michael L

    2015-01-01

    To understand object categorization, participants are tested in experiments often quite different from how people experience object categories in the real world. Learning and knowledge of categories is measured in discrete experimental trials, those trials may or may not provide feedback, trials appear one after another, after some fixed inter-trial interval, with hundreds of trials in a row, within experimental blocks with some structure dictated by the experimental design. In the real world, outside of certain educational and vocational contexts, opportunities to learn and use categories are intermixed over time with a whole multitude of intervening experiences. It is clear from any elementary understanding of human cognition that sequential effects matter, yet this understanding is often ignored, and categorization trials are often instead treated as independent events, immune to local trial context. In this perspective, we use some of our work to illustrate some of the consequences of the fact that categorization experiments have a particular trial structure. Experimental trial context can affect performance in category learning and categorization experiments in ways that can profoundly affect theoretical conclusions.

  1. Trial sequential methods for meta-analysis.

    PubMed

    Kulinskaya, Elena; Wood, John

    2014-09-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual difficulties arise in the random effects model. One approach applying sequential meta-analysis to design is 'trial sequential analysis', developed by Wetterslev, Thorlund, Brok, Gluud and others from the Copenhagen Trial Unit. In trial sequential analysis, information size is based on the required sample size of a single new trial, which, in the random effects model, is obtained by simply inflating it in comparison with fixed effects meta-analysis. However, this is not sufficient as, depending on the amount of heterogeneity, a minimum of several new trials may be indicated, and the total number of new patients needed may be substantially reduced by planning an even larger number of small trials. We provide explicit formulae to determine the requisite minimum number of trials and their sample sizes within this framework, which also exemplify the conceptual difficulties referred to. We illustrate all these points with two practical examples, including the well-known meta-analysis of magnesium for myocardial infarction. Copyright © 2013 John Wiley & Sons, Ltd.

  2. [Situation analysis for drug clinical trial institutions].

    PubMed

    Chen, Yin-Ying; Wu, Ping; Wang, Jie

    2014-08-01

    Drug clinical trial is an important link in the chain of new drug research and development. The results of drug discovery and development directly depend on the extent of standardization of clinical trials. Therefore, improving the quality of drug clinical trials is of great importance, and drug clinical trial institutions play a crucial role in the quality management of drug clinical trials. After years of development, the overall level of drug clinical trials has advanced rapidly in China, and a large number of clinical trials of traditional Chinese medicine have also been carried out. However, there is still a big gap between our country and developed countries. Therefore, for the construction and management of Chinese drug clinical trial institutions, there is still a long way to go. This study aims to analyze the current development of drug clinical trial institutions in China and explore the existing problems from three aspects, including current situations of institutional organization and management, regional and professional distributions, and quality control. And some suggestions are put forward finally, including support of traditional Chinese medicine, introduction of drug-risk management system, and construction of information management.

  3. Terminating a long-term clinical trial.

    PubMed

    Klimt, C R; Canner, P L

    1979-05-01

    Long-term trials often include more than one active treatment group. These may be discontinued independently if found ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet anouther kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.

  4. Terminating a long-term clinical trial.

    PubMed

    Klimt, C R

    1981-05-01

    Long-term clinical trials often include more than one active treatment group. These may be discontinued independently if found to be ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet another kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.

  5. The behavioral dynamics of clinical trials.

    PubMed

    Leventhal, H; Nerenz, D R; Leventhal, E A; Love, R R; Bendena, L M

    1991-01-01

    Two ways of approaching the design of long-term clinical trials are presented and contrasted. The first, termed the "static" view, emphasizes close adherence to formal rules of study design. The second, termed the "dynamic" view, emphasizes the behavioral aspects of patient participation in trials of long duration. The dynamic view is discussed in detail, with discussion of how recruitment of participants, random assignment to conditions, compliance with protocol, and measurement of outcomes are affected by behavioral dynamics. Data from a recently completed tamoxifen toxicity trial are used to illustrate the points and to focus the discussion of behavioral dynamics on the design of a chemoprevention trial for breast cancer using tamoxifen.

  6. Lessons Learned from Radiation Oncology Clinical Trials

    PubMed Central

    Liu, Fei-Fei; Okunieff, Paul; Bernhard, Eric J.; Stone, Helen B.; Yoo, Stephen; Coleman, C. Norman; Vikram, Bhadrasain; Brown, Martin; Buatti, John; Guha, Chandan

    2014-01-01

    A Workshop entitled “Lessons Learned from Radiation Oncology Trials” was held on December 7–8th, 2011 in Bethesda, MD, to present and discuss some of the recently conducted Radiation Oncology clinical trials with a focus on those that failed to refute the null hypothesis. The objectives of this Workshop were to summarize and examine the questions that these trials provoked, to assess the quality and limitations of the pre-clinical data that supported the hypotheses underlying these trials, and to consider possible solutions to these challenges for the design of future clinical trials. Several themes emerged from the discussions, including the: a) opportunities to learn from null-hypothesis trials through tissue and imaging studies; b) value of pre-clinical data supporting the design of combinatorial therapies; c) significance of validated biomarkers; d) necessity of quality assurance in radiotherapy delivery; e) conduct of sufficiently-powered studies to address the central hypothesis; and f) importance of publishing results of the trials regardless of the outcome. The fact that well-designed hypothesis-driven clinical trials produce null or negative results is expected given the limitations of trial design, and complexities of cancer biology. It is important to understand the reasons underlying such null results however, in order to effectively merge the technological innovations with the rapidly evolving biology for maximal patient benefit, through the design of future clinical trials. PMID:24043463

  7. Comparison of arthroplasty trial publications after registration in ClinicalTrials.gov.

    PubMed

    Smith, Holly N; Bhandari, Mohit; Mahomed, Nizar N; Jan, Meryam; Gandhi, Rajiv

    2012-08-01

    In 2005, the International Committee of Medical Journal Editors established a mandatory trial registration before study enrollment for publication in member journals. Our primary objective was to evaluate the publication rates of arthroplasty trials registered with ClinicalTrials.gov (CTG). We further aimed to examine the consistency of registration summaries with that of final publications. We searched CTG for all trials related to joint arthroplasty and conducted a thorough search for publications resulting from registered closed trials. Of 101 closed and completed trials, we found 23 publications, for an overall publication rate of 22.8%. Registration of arthroplasty trials in CTG does not consistently result in publication or disclosure of results. In addition, changes are frequently made to the final presentation of the data that are not reflected in the trial registry.

  8. Adding value to clinical trial registries: insights from Australian Cancer Trials Online, a website for consumers.

    PubMed

    Dear, Rachel; Barratt, Alexandra; Askie, Lisa; McGeechan, Kevin; Arora, Sheena; Crossing, Sally; Currow, David; Tattersall, Martin

    2011-02-01

    Clinical trials registries are now operating in the USA, Europe, Australia, China, and India and more are planned. Trial registries could be an excellent source of information about clinical trials for patients and others affected by cancer as well as health care professionals, but may be difficult for patients to navigate and use. An opportunity arose in Australia to develop a consumer friendly cancer clinical trials website (Australian Cancer Trials Online (ACTO), www.australiancancertrials.gov.au) using an automated data feed from two large clinical trial registries. In this article, we describe aspects of this new website, and explore ways in which such a website may add value to clinical trial data which are already collected and held by trial registries. The development of ACTO was completed by a Web company working in close association with staff at the Australian New Zealand Clinical Trials Registry (ANZCTR), and with consumer representatives. Data for the website were sourced directly and only from clinical trial registries, thus avoiding the creation of an additional trials database. It receives an automated, daily data feed of newly registered cancer clinical trials from both the ANZCTR and Clinical Trials.gov. The development of ACTO exemplifies the advantage of a local clinical trial registry working with consumers to provide accessible information about cancer clinical trials to meet consumers' information needs. We found that the inclusion of a lay summary added substantial value for consumers, and recommend that consideration be given to adding a lay summary to the mandatory data items collected by all trial registries. Furthermore, improved navigation, decision support tools, and consistency in data collection between clinical trial registries will also enable consumer websites to provide additional value for users. Clinical trial registration is not compulsory in Australia. If the additional cancer items (including a lay summary) are not provided

  9. A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence.

    PubMed

    Shoen, Carolyn M; DeStefano, Michelle S; Hager, Cynthia C; Tham, Kyi-Toe; Braunstein, Miriam; Allen, Alexandria D; Gates, Hiriam O; Cynamon, Michael H; Kernodle, Douglas S

    2013-01-11

    Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  10. Strategies to improve retention in randomised trials.

    PubMed

    Brueton, Valerie C; Tierney, Jayne; Stenning, Sally; Harding, Seeromanie; Meredith, Sarah; Nazareth, Irwin; Rait, Greta

    2013-12-03

    Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated. To quantify the effect of strategies to improve retention on the proportion of participants retained in randomised trials and to investigate if the effect varied by trial strategy and trial setting. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO, DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register, and ERIC. We handsearched conference proceedings and publication reference lists for eligible retention trials. We also surveyed all UK Clinical Trials Units to identify further studies. We included eligible retention trials of randomised or quasi-randomised evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. We contacted authors to supplement or confirm data that we had extracted. For retention trials, we recorded data on the method of randomisation, type of strategy evaluated, comparator, primary outcome, planned sample size, numbers randomised and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of the addition of strategies to improve retention. We assessed heterogeneity between trials using the Chi(2) and I(2) statistics. For main trials that hosted retention trials, we extracted data on disease area, intervention, population, healthcare setting, sequence generation and allocation concealment. We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These were incentives, communication strategies, new questionnaire format, participant case

  11. Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications.

    PubMed

    Shepshelovich, D; Goldvaser, H; Wang, L; Abdul Razak, A R; Bedard, P L

    2017-09-14

    Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov , 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21-25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

  12. DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer.

    PubMed

    Thorsen, Lise Bech Jellesmark; Offersen, Birgitte Vrou; Danø, Hella; Berg, Martin; Jensen, Ingelise; Pedersen, Anders Navrsted; Zimmermann, Sune Jürg; Brodersen, Hans-Jürgen; Overgaard, Marie; Overgaard, Jens

    2016-02-01

    It is unknown whether irradiation of the internal mammary lymph nodes improves survival in patients with early-stage breast cancer. A possible survival benefit might be offset by radiation-induced heart disease. We assessed the effect of internal mammary node irradiation (IMNI) in patients with early-stage node-positive breast cancer. In this nationwide, prospective population-based cohort study, we included patients who underwent operation for unilateral early-stage node-positive breast cancer. Patients with right-sided disease were allocated to IMNI, whereas patients with left-sided disease were allocated to no IMNI because of the risk of radiation-induced heart disease. The primary end point was overall survival. Secondary end points were breast cancer mortality and distant recurrence. Analyses were by intention to treat. A total of 3,089 patients were included. Of these, 1,492 patients were allocated to IMNI, whereas 1,597 patients were allocated to no IMNI. With a median of 8.9 years of follow-up time, the 8-year overall survival rates were 75.9% with IMNI versus 72.2% without IMNI. The adjusted hazard ratio (HR) for death was 0.82 (95% CI, 0.72 to 0.94; P = .005). Breast cancer mortality was 20.9% with IMNI versus 23.4% without IMNI (adjusted HR, 0.85; 95% CI, 0.73 to 0.98; P = .03). The risk of distant recurrence at 8 years was 27.4% with IMNI versus 29.7% without IMNI (adjusted HR, 0.89; 95% CI, 0.78 to 1.01; P = .07). The effect of IMNI was more pronounced in patients at high risk of internal mammary node metastasis. Equal numbers in each group died of ischemic heart disease. In this naturally allocated, population-based cohort study, IMNI increased overall survival in patients with early-stage node-positive breast cancer. © 2015 by American Society of Clinical Oncology.

  13. Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy: a DBCG study.

    PubMed

    Lyng, Maria B; Lænkholm, Anne-Vibeke; Søkilde, Rolf; Gravgaard, Karina H; Litman, Thomas; Ditzel, Henrik J

    2012-01-01

    Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables. The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics. Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics.

  14. The Joys of Clinical Trials: A Case Study of a Multicenter Pharmaceutical Trial.

    ERIC Educational Resources Information Center

    Soronson, Bryan M.; Shaw, Diana V.

    1994-01-01

    A discussion of clinical trials in the pharmaceutical industry describes typical processes and administrative issues, then presents a case in which a foreign pharmaceutical company negotiated with a university for sponsorship of a multicenter clinical trial of a new drug therapy. Problems and important considerations in clinical trials are…

  15. The Joys of Clinical Trials: A Case Study of a Multicenter Pharmaceutical Trial.

    ERIC Educational Resources Information Center

    Soronson, Bryan M.; Shaw, Diana V.

    1994-01-01

    A discussion of clinical trials in the pharmaceutical industry describes typical processes and administrative issues, then presents a case in which a foreign pharmaceutical company negotiated with a university for sponsorship of a multicenter clinical trial of a new drug therapy. Problems and important considerations in clinical trials are…

  16. Core outcome sets and trial registries.

    PubMed

    Clarke, Mike; Williamson, Paula

    2015-05-14

    Some reasons for registering trials might be considered as self-serving, such as satisfying the requirements of a journal in which the researchers wish to publish their eventual findings or publicising the trial to boost recruitment. Registry entries also help others, including systematic reviewers, to know about ongoing or unpublished studies and contribute to reducing research waste by making it clear what studies are ongoing. Other sources of research waste include inconsistency in outcome measurement across trials in the same area, missing data on important outcomes from some trials, and selective reporting of outcomes. One way to reduce this waste is through the use of core outcome sets: standardised sets of outcomes for research in specific areas of health and social care. These do not restrict the outcomes that will be measured, but provide the minimum to include if a trial is to be of the most use to potential users. We propose that trial registries, such as ISRCTN, encourage researchers to note their use of a core outcome set in their entry. This will help people searching for trials and those worried about selective reporting in closed trials. Trial registries can facilitate these efforts to make new trials as useful as possible and reduce waste. The outcomes section in the entry could prompt the researcher to consider using a core outcome set and facilitate the specification of that core outcome set and its component outcomes through linking to the original core outcome set. In doing this, registries will contribute to the global effort to ensure that trials answer important uncertainties, can be brought together in systematic reviews, and better serve their ultimate aim of improving health and well-being through improving health and social care.

  17. The L'Aquila trial

    NASA Astrophysics Data System (ADS)

    Amato, Alessandro; Cocco, Massimo; Cultrera, Giovanna; Galadini, Fabrizio; Margheriti, Lucia; Nostro, Concetta; Pantosti, Daniela

    2013-04-01

    The first step of the trial in L'Aquila (Italy) ended with a conviction of a group of seven experts to 6 years of jail and several million euros refund for the families of the people who died during the Mw 6.3 earthquake on April 6, 2009. This verdict has a tremendous impact on the scientific community as well as on the way in which scientists deliver their expert opinions to decision makers and society. In this presentation, we describe the role of scientists in charge of releasing authoritative information concerning earthquakes and seismic hazard and the conditions that led to the verdict, in order to discuss whether this trial represented a prosecution to science, and if errors were made in communicating the risk. Documents, articles and comments about the trial are collected in the web site http://processoaquila.wordpress.com/. We will first summarize what was the knowledge about the seismic hazard of the region and the vulnerability of L'Aquila before the meeting of the National Commission for Forecasting and Predicting Great Risks (CGR) held 6 days before the main shock. The basic point of the accusation is that the CGR suggested that no strong earthquake would have occurred (which of course was never mentioned by any seismologist participating to the meeting). This message would have convinced the victims to stay at home, instead of moving out after the M3.9 and M3.5 earthquakes few hours before the mainshock. We will describe how the available scientific information was passed to the national and local authorities, and in general how the Italian scientific Institution in charge of seismic monitoring and research (INGV), the Civil Protection Department (DPC) and the CGR should interact according to the law. As far as the communication and outreach to the public, the scientific Institutions as INGV have the duty to communicate scientific information. Instead, the risk management and the definition of actions for risk reduction is in charge of Civil

  18. Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry.

    PubMed

    Cihoric, Nikola; Tsikkinis, Alexandros; van Rhoon, Gerard; Crezee, Hans; Aebersold, Daniel M; Bodis, Stephan; Beck, Marcus; Nadobny, Jacek; Budach, Volker; Wust, Peter; Ghadjar, Pirus

    2015-01-01

    Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words. A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia. In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia.

  19. [Internet use in clinical trials].

    PubMed

    Refolo, P; Sacchini, D; Minacori, R; Spagnolo, A G

    2014-01-01

    Recruiting patients is a critical point of today's clinical research and, along the years, several solutions have been proposed, even if their efficacy seems to be doubtful. On the other hand, nowadays, Internet represents a great opportunity for improving clinical trial recruitments. Nevertheless, on-line recruitment services (e-recruitment) could ensure some advantages (such as facilitating interaction between supply and demand of clinical research, time and money savings/optimizations, data entry errors reduction), but also raise some issues (such as those related to sampling, information, consent, real identity of participants and risks for data breaches). The article debates on the difficulties to recruit patients for clinical research, in general, and e-recruitment particularly, discussing some ethical issues raised by internet enrolment.

  20. Clinical Trials in Retinal Dystrophies

    PubMed Central

    Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean

    2016-01-01

    Research development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field – the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges. PMID:26957839

  1. Tuberculosis vaccines in clinical trials

    PubMed Central

    Rowland, Rosalind; McShane, Helen

    2011-01-01

    Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

  2. Trial Sequential Methods for Meta-Analysis

    ERIC Educational Resources Information Center

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  3. THE Social Value of Pragmatic Trials.

    PubMed

    Kalkman, Shona; van Thiel, Ghislaine; van der Graaf, Rieke; Zuidgeest, Mira; Goetz, Iris; Grobbee, Diederick; van Delden, Johannes

    2017-02-01

    Pragmatic trials aim to directly inform health care decision-making through the collection of so-called 'real world data' from observations of comparative treatment effects in clinical practice. In order to ensure the applicability and feasibility of a pragmatic trial, design features may be necessary that deviate from standard research ethics requirements. Examples are traditional requirements to seek written informed consent and to perform extensive data and safety monitoring. Proposals for deviations from standard research ethics practice have resulted in controversy about their ethical acceptability. One of the justifications for altered procedures is the allegedly high social value of pragmatic trials. In order to properly operationalize the concept in the ethical assessment of pragmatic trial designs, specification is warranted. We identified three determinants from common claims about a pragmatic trial's social value: (1) the extent to which the research question has real world relevance, (2) the trial design's ability to generate a real world answer and (3) the probability of direct uptake of the results by decision-makers in practice. Subsequently, we discuss how these determinants should be applied to the practice of pragmatic trials, and to what extent they might be applicable to explanatory trials.

  4. Dialectical Enjoinment During the Scopes Trial.

    ERIC Educational Resources Information Center

    Chandler, Daniel Ross

    This paper examines the Scopes trial's contribution to American intellectual history by studying the historical context of the controversy from a rhetorical perspective. The trial became a rhetorical vehicle which focused on the modernist-fundamentalist religious controversy and polarized these movements. By analyzing the rhetorical…

  5. Feedback after Good Trials Enhances Learning

    ERIC Educational Resources Information Center

    Chiviacowsky, Suzete; Wulf, Gabriele

    2007-01-01

    Recent studies (Chiviacowsky & Wulf, 2002, 2005) have shown that learners prefer to receive feedback after they believe they had a "good" rather than "poor" trial. The present study followed up on this finding and examined whether learning would benefit if individuals received feedback after good relative to poor trials. Participants practiced a…

  6. The Child and Adolescent Psychiatry Trials Network

    ERIC Educational Resources Information Center

    March, John S.; Silva, Susan G.; Compton, Scott; Anthony, Ginger; DeVeaugh-Geiss, Joseph; Califf, Robert; Krishnan, Ranga

    2004-01-01

    Objective: The current generation of clinical trials in pediatric psychiatry often fails to maximize clinical utility for practicing clinicians, thereby diluting its impact. Method: To attain maximum clinical relevance and acceptability, the Child and Adolescent Psychiatry Trials Network (CAPTN) will transport to pediatric psychiatry the practical…

  7. Feedback after Good Trials Enhances Learning

    ERIC Educational Resources Information Center

    Chiviacowsky, Suzete; Wulf, Gabriele

    2007-01-01

    Recent studies (Chiviacowsky & Wulf, 2002, 2005) have shown that learners prefer to receive feedback after they believe they had a "good" rather than "poor" trial. The present study followed up on this finding and examined whether learning would benefit if individuals received feedback after good relative to poor trials. Participants practiced a…

  8. Homo Economicus and the Salem Witch Trials.

    ERIC Educational Resources Information Center

    Mixon, Franklin G., Jr.

    2000-01-01

    Provides background information on the Salem Witch Trials (Salem, Massachusetts) and the medical explanation of the young village girls' behavior in Salem called ergotism (bread poisoning). Presents an economic interpretation of those trials, stating that the ministers employed religious beliefs about witchcraft to maintain their churchs' monopoly…

  9. Homo Economicus and the Salem Witch Trials.

    ERIC Educational Resources Information Center

    Mixon, Franklin G., Jr.

    2000-01-01

    Provides background information on the Salem Witch Trials (Salem, Massachusetts) and the medical explanation of the young village girls' behavior in Salem called ergotism (bread poisoning). Presents an economic interpretation of those trials, stating that the ministers employed religious beliefs about witchcraft to maintain their churchs' monopoly…

  10. 50 CFR 27.91 - Field trials.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Field trials. 27.91 Section 27.91 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE... conducting or operation of field trials for dogs on national wildlife refuges is prohibited except as may...

  11. A primer on effectiveness and efficacy trials.

    PubMed

    Singal, Amit G; Higgins, Peter D R; Waljee, Akbar K

    2014-01-02

    Although efficacy and effectiveness studies are both important when evaluating interventions, they serve distinct purposes and have different study designs. Unfortunately, the distinction between these two types of trials is often poorly understood. In this primer, we highlight several differences between these two types of trials including study design, patient populations, intervention design, data analysis, and result reporting.

  12. Estimating Single-Trial Responses in EEG

    NASA Technical Reports Server (NTRS)

    Shah, A. S.; Knuth, K. H.; Truccolo, W. A.; Mehta, A. D.; Fu, K. G.; Johnston, T. A.; Ding, M.; Bressler, S. L.; Schroeder, C. E.; Clancy, Daniel (Technical Monitor)

    2002-01-01

    Accurate characterization of single-trial field potential responses is critical from a number of perspectives. For example, it allows differentiation of an evoked response from ongoing EEG. We previously developed the multiple component Event Related Potential (mcERP) algorithm to improve resolution of the single-trial evoked response. The mcERP model states that multiple components, each specified by a stereotypic waveform varying in latency and amplitude from trial to trial, comprise the evoked response. Application of the mcERP algorithm to simulated data with three independent, synthetic components has shown that the model is capable of separating these components and estimating their variability. Application of the model to single trial, visual evoked potentials recorded simultaneously from all V1 laminae in an awake, fixating macaque yielded local and far-field components. Certain local components estimated by the model were distributed in both granular and supragranular laminae. This suggests a linear coupling between the responses of thalamo-recipient neuronal ensembles and subsequent responses of supragranular neuronal ensembles, as predicted by the feedforward anatomy of V1. Our results indicate that the mcERP algorithm provides a valid estimation of single-trial responses. This will enable analyses that depend on trial-to-trial variations and those that require separation of the evoked response from background EEG rhythms

  13. Estimating Single-Trial Responses in EEG

    NASA Technical Reports Server (NTRS)

    Shah, A. S.; Knuth, K. H.; Truccolo, W. A.; Mehta, A. D.; Fu, K. G.; Johnston, T. A.; Ding, M.; Bressler, S. L.; Schroeder, C. E.; Clancy, Daniel (Technical Monitor)

    2002-01-01

    Accurate characterization of single-trial field potential responses is critical from a number of perspectives. For example, it allows differentiation of an evoked response from ongoing EEG. We previously developed the multiple component Event Related Potential (mcERP) algorithm to improve resolution of the single-trial evoked response. The mcERP model states that multiple components, each specified by a stereotypic waveform varying in latency and amplitude from trial to trial, comprise the evoked response. Application of the mcERP algorithm to simulated data with three independent, synthetic components has shown that the model is capable of separating these components and estimating their variability. Application of the model to single trial, visual evoked potentials recorded simultaneously from all V1 laminae in an awake, fixating macaque yielded local and far-field components. Certain local components estimated by the model were distributed in both granular and supragranular laminae. This suggests a linear coupling between the responses of thalamo-recipient neuronal ensembles and subsequent responses of supragranular neuronal ensembles, as predicted by the feedforward anatomy of V1. Our results indicate that the mcERP algorithm provides a valid estimation of single-trial responses. This will enable analyses that depend on trial-to-trial variations and those that require separation of the evoked response from background EEG rhythms

  14. Controversy, Trials, and Crime--Oh My!

    ERIC Educational Resources Information Center

    Rott, Kim

    2006-01-01

    Teenagers' innate interest with the justice system is one of the reasons that so many high school literary classics teem with criminals, controversial issues, and trials. Novels such as "To Kill a Mockingbird," "A Separate Peace," "The Crucible," and "Twelve Angry Men" feature high-impact trials. In the author's desire to tap into this interest,…

  15. The Child and Adolescent Psychiatry Trials Network

    ERIC Educational Resources Information Center

    March, John S.; Silva, Susan G.; Compton, Scott; Anthony, Ginger; DeVeaugh-Geiss, Joseph; Califf, Robert; Krishnan, Ranga

    2004-01-01

    Objective: The current generation of clinical trials in pediatric psychiatry often fails to maximize clinical utility for practicing clinicians, thereby diluting its impact. Method: To attain maximum clinical relevance and acceptability, the Child and Adolescent Psychiatry Trials Network (CAPTN) will transport to pediatric psychiatry the practical…

  16. Trial Sequential Methods for Meta-Analysis

    ERIC Educational Resources Information Center

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  17. North West Shelf Unmanned Aerial System Trial

    DTIC Science & Technology

    2007-02-01

    North West Shelf Unmanned Aerial System Trial Duncan Craig Intelligence, Surveillance and Reconnaissance Division Defence... Unmanned Aerial System Trial Executive Summary In response to a government policy announcement issued during the lead-up to the 2004...federal election, Defence invited General Atomics Aeronautical Systems Incorporated (GA-ASI) and Northrop Grumman (NG) to participate in an Unmanned Aerial System (UAS

  18. 25 CFR 11.313 - Trial procedure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Trial procedure. 11.313 Section 11.313 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Criminal Procedure § 11.313 Trial procedure. (a) The time and place of court sessions, and all other...

  19. 37 CFR 11.306 - Trial publicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Trial publicity. 11.306 Section 11.306 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT... of Professional Conduct Advocate § 11.306 Trial publicity. (a) A practitioner who is participating or...

  20. 25 CFR 11.313 - Trial procedure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Trial procedure. 11.313 Section 11.313 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Criminal Procedure § 11.313 Trial procedure. (a) The time and place of court sessions, and all other...

  1. 25 CFR 11.313 - Trial procedure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Trial procedure. 11.313 Section 11.313 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Criminal Procedure § 11.313 Trial procedure. (a) The time and place of court sessions, and all other...

  2. 25 CFR 11.313 - Trial procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Trial procedure. 11.313 Section 11.313 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Criminal Procedure § 11.313 Trial procedure. (a) The time and place of court sessions, and all other...

  3. Controversy, Trials, and Crime--Oh My!

    ERIC Educational Resources Information Center

    Rott, Kim

    2006-01-01

    Teenagers' innate interest with the justice system is one of the reasons that so many high school literary classics teem with criminals, controversial issues, and trials. Novels such as "To Kill a Mockingbird," "A Separate Peace," "The Crucible," and "Twelve Angry Men" feature high-impact trials. In the author's desire to tap into this interest,…

  4. Neuroprotection trials in Parkinson's disease: systematic review.

    PubMed

    Hart, Robert G; Pearce, Lesly A; Ravina, Bernard M; Yaltho, Toby C; Marler, John R

    2009-04-15

    Treatments to slow the progression are a major unmet need in Parkinson's disease. Detailed assessment of randomized trials testing putative neuroprotective drugs was undertaken to inform the design, reporting, and interpretation of future studies. This study is a systematic review of trials testing neuroprotective drugs. Data were extracted independently by two coauthors. Fifteen completed, published trials involving 4,087 participants tested 13 different drugs in 18 double-blind comparisons with placebo. Seven comparisons involving 2,000 subjects assessed MAO-B inhibitors. The primary outcome was change in the Unified Parkinson's Disease Rating Scale score in eight trials and time to need for dopaminergic therapy in seven. Mean participant age was 62 years, 35% were women, the interval from diagnosis to entry averaged 11 months, and the number of participants averaged 272 (largest = 806). Follow-up averaged <16 months in all but two trials. Detailed randomization methods and success of double-blinding were reported in 20% and 13%, respectively. Based on the investigators' conclusions, six trials were interpreted as consistent with a neuroprotective effect, three as negative, and five as either confounded or not meeting criteria for futility. Neuroprotection trials have involved relatively uniform groups of participants early in the clinical disease course, with outcomes weighted heavily toward motor deterioration. Future trials should include participants with wider ranges of disease stages and assess broader neurological outcomes.

  5. Clinical Trials: Key to Medical Progress

    MedlinePlus

    ... to control high blood pressure. There are clinical trials going on all the time in nearly every area of medical research. To Find Out More To find out more about clinical trials and how to participate, go to: www.clinicaltrials. ...

  6. 25 CFR 11.313 - Trial procedure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Trial procedure. 11.313 Section 11.313 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Criminal Procedure § 11.313 Trial procedure. (a) The time and place of court sessions, and all other...

  7. Canadian MSAT field trial program user requirements

    NASA Technical Reports Server (NTRS)

    Pedersen, Allister

    1990-01-01

    A wide range of mobile satellite service offerings will be available in late 1993 with the launch of Canada's first satellite devoted almost exclusively to mobile and transportable services. During the last seven years, the Dept. of Communications has been meeting with potential MSAT users in government and the private sector as part of a $20M Communications Trials Program. User trials will be conducted using leased capacity as well as capacity on Canada's MSAT satellite. User requirements are discussed which were identified under the Communications Trials Program. Land, marine, aeronautical, and fixed applications are described from the perspective of the end users. Emphasis is placed on field trials being accomplished using leased capacity such as the marine data trial being implemented by Ultimateast Data Communications, trials using transportable briefcase terminals and additional field trials being considered for implementation with the TMI Mobile Data Service. The pre-MSAT trials that will be conducted using leased capacity are only a limited sample of the overall end user requirements that have been identified to date. Additional end user applications are discussed, along with a summary of user benefits.

  8. Lessons from the SYNTAX trial.

    PubMed

    Alamri, Hussein S; Alotaiby, Mohammed; Almoghairi, Abdulrahman; El Oakley, Rieda M

    2010-04-01

    Despite the fact that CABG is the standard of care for patients with multivessel coronary arteries and/or left main stem stenosis, PCI has become a rival to CABG in patients with multivessel coronary artery disease or left main disease. However, the need for repeat revascularization, in-stent stenosis and thrombosis remain the achilis heal of PCI. SYNTAX trial randomized patients with left main disease and/or three-vessel disease to PCI with TAXus stent or CABG with the concept that PCI is not inferior to CABG. At 1 and 2 years follow up, MACCE was significantly increased in PCI patients mainly attributed to increased rate of repeat revascularization; however, stroke was significantly more with CABG. The composite safety endpoint of death/stroke/MI was comparable between the 2 groups. Therefore the criterion for non-inferiority was not met. What we learn from SYNTAX is that multi disciplinary team approach should be the standard of care when recommending treatment in more complex coronary artery disease. SYNTAX makes interventionists and surgeons come together, it may set the benchmark for MVD revascularization. PCI and CABG should be considered complementary rather than competitive revascularization strategies. There is no substitute for sound clinical judgment that takes into account the patient's overall clinical profile, functionality, co-morbidities, as well as the patient's coronary anatomy. The SYNTAX Score should be utilized to decide on treatment of patients with LM/MVD. Patients with low and intermediate score can be treated with PCI or CABG with equal results. Those with high score do better with CABG. SYNTAX trial showed that 66% of patients with 3VD or LMD are still best treated with CABG. In the remaining 1/3 of patients with low syntax score, PCI may be considered as an alternative to surgery. Finally, medical treatment should be optimized in patients going for CABG.

  9. Clinical Trials and the Role of the Oncology Clinical Trials Nurse.

    PubMed

    Ness, Elizabeth A; Royce, Cheryl

    2017-03-01

    Clinical trials are paramount to improving human health. New trial designs and informed consent issues are emerging as a result of genomic profiling and the development of molecularly targeted agents. Many groups and individuals are responsible for ensuring the protection of research participants and the quality of the data produced. The specialty role of the clinical trials nurse (CTN) is critical to clinical trials. Oncology CTNs have competencies that can help guide their practice; however, not all oncology clinical trials are supervised by a nurse. Using the process of engagement, one organization has restructured oncology CTNs under a nurse-supervised model.

  10. Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals.

    PubMed

    Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

    2013-12-01

    The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45

  11. Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

    PubMed Central

    Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

    2013-01-01

    Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0

  12. Internet trials: participant experiences and perspectives.

    PubMed

    Mathieu, Erin; Barratt, Alexandra; Carter, Stacy M; Jamtvedt, Gro

    2012-10-23

    Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants' attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate). Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants' comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience - a perceived benefit - and a lack connectedness and understanding - a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet; security, privacy and confidentiality issues; perceived benefits and

  13. Sample Size Estimation in Clinical Trial

    PubMed Central

    Sakpal, Tushar Vijay

    2010-01-01

    Every clinical trial should be planned. This plan should include the objective of trial, primary and secondary end-point, method of collecting data, sample to be included, sample size with scientific justification, method of handling data, statistical methods and assumptions. This plan is termed as clinical trial protocol. One of the key aspects of this protocol is sample size estimation. The aim of this article is to discuss how important sample size estimation is for a clinical trial, and also to understand the effects of sample size over- estimation or under-estimation on outcome of a trial. Also an attempt is made to understand importance of minimum sample to detect a clinically important difference. This article is also an attempt to provide inputs on different parameters that impact sample size and basic rules for these parameters with the help of some simple examples. PMID:21829786

  14. Marketing and clinical trials: a case study

    PubMed Central

    Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

    2007-01-01

    Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors. PMID:18028537

  15. Paperless clinical trials: Myth or reality?

    PubMed Central

    Gupta, Sandeep K.

    2015-01-01

    There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464

  16. Marketing and clinical trials: a case study.

    PubMed

    Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

    2007-11-20

    Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

  17. Ethics of clinical trials in Nigeria

    PubMed Central

    Okonta, Patrick I.

    2014-01-01

    The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria. PMID:25013247

  18. A primer on randomized controlled trials.

    PubMed

    Likosky, Donald S

    2006-03-01

    Randomized Clinical Trials are held as the gold standard for quantifying the effect of an intervention across two or more groups. In such a trial an intervention is randomly allocated to one of two groups. The benefit of such a trial lies in its ability to establish nearly comparable groups of subjects in all manner except for the effect of the intervention. As such, the effect of a given intervention may be attributed solely to the intervention and not to any other extraneous factor. In the following editorial, we will discuss several issues that are important for understanding how to conduct and interpret randomized trials: choosing the study population, choosing the comparison group, choosing your outcome, study design, data analysis, and issues of inference. This editorial is intended to make the reader an educated consumer of such trial designs.

  19. Single-Trial Inference on Visual Attention

    NASA Astrophysics Data System (ADS)

    Dyrholm, Mads; Kyllingsbæk, Søren; Vangkilde, Signe; Habekost, Thomas; Bundesen, Claus

    2011-06-01

    In this paper we take a step towards single-trial behavioral modeling within a Theory of Visual Attention (TVA). In selective attention tasks, such as the Partial Report paradigm, the subject is asked to ignore distractors and only report stimuli that belong to the target class. Nothing about a distractor is observed directly in the subject's overt behavior, hence behavioral modeling of such trials involves out-marginalizing the variables that represent the distractors' influence on behavior. In this paper we derive equations for inferring a latent representation of the distractors on a Partial Report trial. This result retrodicts a latent attentional state of the subject using the observed response from that particular trial and thus differs from other predictions made with TVA which are based on expected values of observed variables. We show an example of the result in single-trial analysis of an occipital EEG component.

  20. Do trials of perpetrators retraumatize crime victims?

    PubMed

    Orth, Ulrich; Maercker, Andreas

    2004-02-01

    Attendance at trials of perpetrators could be retraumatizing for crime victims suffering from posttraumatic stress disorder. To investigate this hypothesis, two studies were conducted in which retraumatization was defined as a significant increase in posttraumatic stress reactions. A cross-sectional study of 137 victims of rape and nonsexual assault revealed that trial variables do virtually not predict posttraumatic stress reactionsat a time several years after trial. A longitudinal study of 31 victims of rape and nonsexual assault revealed intraindividual stability of posttraumatic stress reactions for the time interval from a few weeks before the trial to a few weeks after the trial; in addition, interindividual stability was high. The results of both studies do not support the retraumatization hypothesis, which should therefore be used with caution.

  1. Methodological Issues in Negative Symptom Trials

    PubMed Central

    Marder, Stephen R.; Daniel, David G.; Alphs, Larry; Awad, A. George; Keefe, Richard S. E.

    2011-01-01

    Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms. PMID:21270473

  2. Clinical trials in Russia: achieving excellence

    NASA Astrophysics Data System (ADS)

    Reznik, Robert S.; Ichim, Thomas E.; Petrov, Vladimir; Reznik, Boris N.

    2005-06-01

    The Russian population offers a unique opportunity for conducting clinical trials in general, and specifically in the area of Medical Devices. Although the regulatory framework for approval of clinical trials and eventual marketing registration is based on an American-style format, details of operating in the Russian framework are very different. Understanding and leveraging the unique characteristics of the Russian system on the patient side, the investigator side, and the regulatory side is important in extracting optimum value out of clinical trials in Russia. Having performed Medical Device research and clinical trials in Russia, the authors overview the present system and describe various strategies for working in this growing but still under-utilized clinical trials arena.

  3. Methodological issues in negative symptom trials.

    PubMed

    Marder, Stephen R; Daniel, David G; Alphs, Larry; Awad, A George; Keefe, Richard S E

    2011-03-01

    Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms.

  4. Ethics of clinical trials in Nigeria.

    PubMed

    Okonta, Patrick I

    2014-05-01

    The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria.

  5. Risk-proportionate clinical trial monitoring: an example approach from a non-commercial trials unit.

    PubMed

    Tudur Smith, Catrin; Williamson, Paula; Jones, Ashley; Smyth, Alan; Hewer, Simon Langton; Gamble, Carrol

    2014-04-16

    Some level of monitoring is usually required during a clinical trial to protect the rights and safety of trial participants and to safeguard the quality and reliability of trial results. Although there is increasing support for the use of risk-proportionate approaches to achieve these aims, the variety of methods and lack of an empirical evidence base can present challenges for clinical trial practitioners. This paper describes the monitoring methods and procedures that are utilised by a non-commercial clinical trials unit which coordinates a range of clinical trials across a variety of clinical areas with different associated risks. Monitoring activities and approaches should be selected to be proportionate to the risks identified within a trial. A risk-proportionate approach to monitoring is described giving details of methods that may be considered by clinical trial practitioners during the development of a trial monitoring plan. An example risk assessment and corresponding monitoring plan for a low risk (type A in the Medicines and Healthcare Products Regulatory Agency (MHRA) classification system) pediatric trial is provided for illustration. We present ideas for developing a monitoring plan for a clinical trial of an investigational medicinal product based on our experience. Alternative approaches may be relevant or preferable in other settings based on inherent risk.

  6. Risk-proportionate clinical trial monitoring: an example approach from a non-commercial trials unit

    PubMed Central

    2014-01-01

    Background Some level of monitoring is usually required during a clinical trial to protect the rights and safety of trial participants and to safeguard the quality and reliability of trial results. Although there is increasing support for the use of risk-proportionate approaches to achieve these aims, the variety of methods and lack of an empirical evidence base can present challenges for clinical trial practitioners. Methods This paper describes the monitoring methods and procedures that are utilised by a non-commercial clinical trials unit which coordinates a range of clinical trials across a variety of clinical areas with different associated risks. Results Monitoring activities and approaches should be selected to be proportionate to the risks identified within a trial. A risk-proportionate approach to monitoring is described giving details of methods that may be considered by clinical trial practitioners during the development of a trial monitoring plan. An example risk assessment and corresponding monitoring plan for a low risk (type A in the Medicines and Healthcare Products Regulatory Agency (MHRA) classification system) pediatric trial is provided for illustration. Conclusion We present ideas for developing a monitoring plan for a clinical trial of an investigational medicinal product based on our experience. Alternative approaches may be relevant or preferable in other settings based on inherent risk. PMID:24739398

  7. Trial of Repeated Analgesia with Kangaroo Mother Care (TRAKC Trial)

    PubMed Central

    2013-01-01

    preferred standard of care. However, current pain management guidelines are based on minimal data on repeated use of either intervention. Therefore, regardless of the outcomes of this study, results will have important implications for guidelines and practices related to management of procedural pain in preterm infants. Trial registration ClinicalTrials.gov Identifier: NCT01561547. PMID:24284002

  8. Automated information extraction of key trial design elements from clinical trial publications.

    PubMed

    de Bruijn, Berry; Carini, Simona; Kiritchenko, Svetlana; Martin, Joel; Sim, Ida

    2008-11-06

    Clinical trials are one of the most valuable sources of scientific evidence for improving the practice of medicine. The Trial Bank project aims to improve structured access to trial findings by including formalized trial information into a knowledge base. Manually extracting trial information from published articles is costly, but automated information extraction techniques can assist. The current study highlights a single architecture to extract a wide array of information elements from full-text publications of randomized clinical trials (RCTs). This architecture combines a text classifier with a weak regular expression matcher. We tested this two-stage architecture on 88 RCT reports from 5 leading medical journals, extracting 23 elements of key trial information such as eligibility rules, sample size, intervention, and outcome names. Results prove this to be a promising avenue to help critical appraisers, systematic reviewers, and curators quickly identify key information elements in published RCT articles.

  9. Methodology of superiority vs. equivalence trials and non-inferiority trials.

    PubMed

    Christensen, Erik

    2007-05-01

    The randomized clinical trial (RCT) is generally accepted as the best method of comparing effects of therapies. Most often the aim of an RCT is to show that a new therapy is superior to an established therapy or placebo, i.e. they are planned and performed as superiority trials. Sometimes the aim of an RCT is just to show that a new therapy is not superior but equivalent to or not inferior to an established therapy, i.e. they are planned and performed as equivalence trials or non-inferiority trials. Since the types of trials have different aims, they differ significantly in various methodological aspects. The awareness of the methodological differences is generally quite limited. This paper reviews the methodology of these types of trials with special reference to differences in respect to planning, performance, analysis and reporting of the trial. In this context the relevant basal statistical concepts are reviewed. Some of the important points are illustrated by examples.

  10. Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies.

    PubMed

    Lin, Ja-An; He, Pei

    2015-06-01

    Recently, new clinical trial designs involving biomarkers have been studied and proposed in cancer clinical research, in the hope of incorporating the rapid growing basic research into clinical practices. Journal articles related to various biomarkers and their role in cancer clinical trial, articles and books about statistical issues in trial design, and regulatory website, documents, and guidance for submission of targeted cancer therapies. The drug development process involves four phases. The confirmatory Phase III is essential in regulatory approval of a special treatment. Regulatory agency has restrictions on confirmatory trials 'using adaptive designs'. No rule of thumb to pick the most appropriate design for biomarker-related trials. Statistical issues to solve in new designs. Regulatory acceptance of the 'newly proposed trial designs'. Biomarker-related trial designs that can resolve the statistical issues and satisfy the regulatory requirement. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. What Are the Possible Benefits and Risks of Clinical Trials?

    MedlinePlus

    ... Sponsors Why Are They Important How Do They Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites What Are the ...

  12. Characteristics of pediatric pulmonary hypertension trials registered on ClinicalTrials.gov.

    PubMed

    Awerbach, Jordan D; Krasuski, Richard A; Hill, Kevin D

    2017-01-01

    The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs. Interventional pediatric (ages 0-17 years) PH trials registered on ClinicalTrials.gov from June 2005 through December 2014 were analyzed. There were 45 pediatric PH trials registered during the study period. Median (IQR) projected trial enrollment was 40 (24-63), with seven trials (16%) targeting > 100 participants. Industry was the most common trial sponsor (n = 23, 50%), with only two (4.4%) NIH-sponsored trials. Phosphodiesterase inhibitors were the most frequently studied drug (n = 18, 39%). Single group study designs were used in 44% (n = 20) with an active comparator (parallel, factorial, or cross-over designs) in 25 trials, including 22 with randomization and ten that were double-blinded. Study outcomes varied markedly with inconsistent use of known surrogate and composite endpoints. One-third of trials (n = 15, 33%) were terminated, predominantly due to poor participant enrollment. Of the 17 completed trials, 11 had published results and only three efficacy trials met their primary endpoint. There are unique challenges to drug development in pediatric PH, including enrolling patients, identifying appropriate study endpoints, and conducting randomized, controlled, double-blind trials where the likelihood of meeting the study endpoint is optimized.

  13. Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

    PubMed

    Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

    2012-05-02

    Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0

  14. Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials.

    PubMed

    Dechartres, Agnes; Bond, Elizabeth G; Scheer, Jordan; Riveros, Carolina; Atal, Ignacio; Ravaud, Philippe

    2016-11-30

    Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. We searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported. From the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001-0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005-0.59). Half of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant

  15. Strategies to improve retention in randomised trials

    PubMed Central

    Brueton, Valerie C; Tierney, Jayne; Stenning, Sally; Harding, Seeromanie; Meredith, Sarah; Nazareth, Irwin; Rait, Greta

    2013-01-01

    Background Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated. Objectives To quantify the effect of strategies to improve retention on the proportion of participants retained in randomised trials and to investigate if the effect varied by trial strategy and trial setting. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO, DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register, and ERIC. We handsearched conference proceedings and publication reference lists for eligible retention trials. We also surveyed all UK Clinical Trials Units to identify further studies. Selection criteria We included eligible retention trials of randomised or quasi-randomised evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. Data collection and analysis We contacted authors to supplement or confirm data that we had extracted. For retention trials, we recorded data on the method of randomisation, type of strategy evaluated, comparator, primary outcome, planned sample size, numbers randomised and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of the addition of strategies to improve retention. We assessed heterogeneity between trials using the Chi2 and I2 statistics. For main trials that hosted retention trials, we extracted data on disease area, intervention, population, healthcare setting, sequence generation and allocation concealment. Main results We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These

  16. The Mycotic Ulcer Treatment Trial

    PubMed Central

    Prajna, N. Venkatesh; Krishnan, Tiruvengada; Mascarenhas, Jeena; Rajaraman, Revathi; Prajna, Lalitha; Srinivasan, Muthiah; Raghavan, Anita; Oldenburg, Catherine E.; Ray, Kathryn J.; Zegans, Michael E.; McLeod, Stephen D.; Porco, Travis C.; Acharya, Nisha R.; Lietman, Thomas M.

    2013-01-01

    Objective To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis. Methods This phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400. Main Outcome Measures The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty. Results A total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycin-treated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=−0.18 logMAR; 95% CI, −0.30 to −0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=−0.41 logMAR; 95% CI, −0.61 to −0.20; P<.001; odds ratio for perforation=0.06; 95% CI, 0.01 to 0.28; P<.001), while non-Fusarium cases fared similarly (regression coefficient=−0.02 logMAR; 95% CI, −0.17 to 0.13; P=.81; odds ratio for perforation=1.08; 95% CI, 0.48 to 2.43; P=.86). Conclusions Natamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases. Application to Clinical Practice Voriconazole should not be used as monotherapy in filamentous keratitis. Trial Registration

  17. Clinical trial registration in oral health journals.

    PubMed

    Smaïl-Faugeron, V; Fron-Chabouis, H; Durieux, P

    2015-03-01

    Prospective registration of randomized controlled trials (RCTs) represents the best solution to reporting bias. The extent to which oral health journals have endorsed and complied with RCT registration is unknown. We identified journals publishing RCTs in dentistry, oral surgery, and medicine in the Journal Citation Reports. We classified journals into 3 groups: journals requiring or recommending trial registration, journals referring indirectly to registration, and journals providing no reference to registration. For the 5 journals with the highest 2012 impact factors in each group, we assessed whether RCTs with results published in 2013 had been registered. Of 78 journals examined, 32 (41%) required or recommended trial registration, 19 (24%) referred indirectly to registration, and 27 (35%) provided no reference to registration. We identified 317 RCTs with results published in the 15 selected journals in 2013. Overall, 73 (23%) were registered in a trial registry. Among those, 91% were registered retrospectively and 32% did not report trial registration in the published article. The proportion of trials registered was not significantly associated with editorial policies: 29% with results in journals that required or recommended registration, 15% in those that referred indirectly to registration, and 21% in those providing no reference to registration (P = 0.05). Less than one-quarter of RCTs with results published in a sample of oral health journals were registered with a public registry. Improvements are needed with respect to how journals inform and require their authors to register their trials. © International & American Associations for Dental Research.

  18. Clinical Trials For Cytoprotection In Stroke

    PubMed Central

    Labiche, Lise A.; Grotta, James C.

    2004-01-01

    Summary: To date, many cytoprotective drugs have reached the stage of pivotal phase 3 efficacy trials in acute stroke patients. (Table 1) Unfortunately, throughout the neuroprotective literature, the phrase “failure to demonstrate efficacy” prevails as a common thread among the many neutral or negative trials, despite the largely encouraging results encountered in preclinical studies. The reasons for this discrepancy are multiple, and have been discussed by Dr. Zivin in his review. Many of the recent trials have addressed deficiencies of the previous ones with more rigorous trial design, including more specific patient selection criteria (ensure homogeneity of stroke location and severity), stratified randomization algorithms (time-to-treat), narrowed therapeutic time-window and pharmacokinetic monitoring. Current trials have also incorporated biologic surrogate markers of toxicity and outcome such as drug levels and neuroimaging. Lastly, multi-modal therapies and coupled cytoprotection/reperfusion strategies are being investigated to optimize tissue salvage. This review will focus on individual therapeutic strategies and we will emphasize what we have learned from these trials both in terms of trial design and the biologic effect (or lack thereof) of these agents. PMID:15717007

  19. Justifying clinical trials for porcine islet xenotransplantation.

    PubMed

    Ellis, Cara E; Korbutt, Gregory S

    2015-01-01

    The development of the Edmonton Protocol encouraged a great deal of optimism that a cell-based cure for type I diabetes could be achieved. However, donor organ shortages prevent islet transplantation from being a widespread solution as the supply cannot possibly equal the demand. Porcine islet xenotransplantation has the potential to address these shortages, and recent preclinical and clinical trials show promising scientific support. Consequently, it is important to consider whether the current science meets the ethical requirements for moving toward clinical trials. Despite the potential risks and the scientific unknowns that remain to be investigated, there is optimism regarding the xenotransplantation of some types of tissue, and enough evidence has been gathered to ethically justify clinical trials for the most safe and advanced area of research, porcine islet transplantation. Researchers must make a concerted effort to maintain a positive image for xenotransplantation, as a few well-publicized failed trials could irrevocably damage public perception of xenotransplantation. Because all of society carries the burden of risk, it is important that the public be involved in the decision to proceed. As new information from preclinical and clinical trials develops, policy decisions should be frequently updated. If at any point evidence shows that islet xenotransplantation is unsafe, then clinical trials will no longer be justified and they should be halted. However, as of now, the expected benefit of an unlimited supply of islets, combined with adequate informed consent, justifies clinical trials for islet xenotransplantation.

  20. From randomised trials to rational practice.

    PubMed

    van Gijn, J

    2005-01-01

    From the age of Enlightenment onwards, philosophical thinking has become increasingly influenced by empiricism: observations lead to theories, but experiments are needed to put the reasoning to the test. However, it was not until the middle of the 20th century that well-designed experiments were at last introduced in medical treatment, in the form of randomised controlled clinical trials. This design is now standard in medicine, but in everyday practice a multitude of management decisions must still be taken without good evidence. There are several reasons for this: there may not be a trial at all or only a single trial; trial results may be equivocal; patients may be different from those enrolled in trials; new procedures require practice, or a trial may not be feasible. 'Logical reasoning', with all its fallacies, is still required - not only to fill the gaps in empirical knowledge but also to interpret existing evidence and to plan new trials. In fact, the generation of new knowledge is a continuous, cyclical process in which newly gained insights in pathophysiology give rise to new therapeutic experiments, the results of which generate fresh hypotheses, and so on. Compassion, curiosity and doubt are the essential forces that keep the cycle moving. Conversely, the progress is slowed down by present-day legalism, which distorts investigator accountability and patient autonomy. Copyright (c) 2005 S. Karger AG, Basel.

  1. Status of the pediatric clinical trials enterprise: an analysis of the US ClinicalTrials.gov registry.

    PubMed

    Pasquali, Sara K; Lam, Wendy K; Chiswell, Karen; Kemper, Alex R; Li, Jennifer S

    2012-11-01

    Clinical trials are the gold standard for generating evidence-based knowledge in medicine. Recent legislation requiring trials to be registered at ClinicalTrials.gov has enabled evaluation of the clinical trial enterprise as a whole, which was previously not possible. The purpose of this study was to create a snapshot of the pediatric clinical trial portfolio. All interventional trials registered at ClinicalTrials.gov from July 2005 to September 2010 were included. Pediatric (ie, enrolling patients aged 0-18 years) trial characteristics, therapeutic area, location, and funding were described. Secondary objectives included describing pediatric trials over time and comparison with nonpediatric trials. During this time, 5035 pediatric trials were registered compared with >10 times as many nonpediatric trials. Neonates/infants were eligible for enrollment in 46.6% of trials versus children (77.9%) and adolescents (45.2%). Nearly one-half of pediatric trials enrolled <100 subjects, and more pediatric trials versus nonpediatric trials evaluated preventive therapies. The proportion of pediatric trials evaluating a drug intervention declined over time, and there were fewer Phase 0 to II versus Phase III to IV trials. Infectious disease/vaccine studies (23%) were the most common, followed by psychiatric/mental health (13%) studies. Many trials enrolled patients outside the United States, and <15% of trials were sponsored by the National Institutes of Health or other US federal agencies. Analysis of the ClinicalTrials.gov data set allows description of the current scope of pediatric trials. These data may be useful to stakeholders in informing decisions regarding the conduct of trials in children and provide insight into mechanisms to advance pediatric trial infrastructure and methodology toward improving child health.

  2. Willingness to participate in HIV vaccine trials: The impact of trial attributes

    PubMed Central

    Newman, Peter A.; Duan, Naihua; Lee, Sung-Jae; Rudy, Ellen; Seiden, Danielle; Kakinami, Lisa; Cunningham, William

    2010-01-01

    Objectives To assess willingness to participate (WTP) in hypothetical Phase III preventive HIV vaccine trials, and the impact of trial attributes on WTP, among low socioeconomic, ethnically diverse adults from communities at elevated risk for HIV infection. Method Participants (n=123; median age=38; 69% male; 37% Latino; 14% African-American) were recruited in Los Angeles in 2003 using multi-site, venue-based sampling. WTP was assessed for eight hypothetical HIV vaccine trials that varied across seven dichotomous attributes, using a 27-4 fractional factorial experimental design. Individual-specific impact of vaccine trial attributes on WTP was estimated using within-individual ANOVA and then meta-analyzed across individuals. Results Mean WTP for eight hypothetical vaccine trials ranged from 1.74 to 3.81 (1=highly unlikely, 5=highly likely). Lower WTP was associated with vaccine-induced infection risk (impact=0.88, p<0.0001), false HIV-positives (0.53, p<0.0001), no provision of free HIV medications (0.52, p<0.0001), and longer trial duration (0.27; p=0.0002). Conclusion HIV vaccine trial attributes may strongly influence WTP. Although existing candidate vaccines cannot cause HIV infection, perceptions of risk may impede WTP. Eliciting trial preferences and concerns prior to trial implementation may enable accommodation of participant preferences and support tailored interventions to address concerns and misconceptions to facilitate enrollment in safe and ethical trials among vulnerable communities. PMID:17275895

  3. Are explanatory trials ethical? Shifting the burden of justification in clinical trial design.

    PubMed

    Borgerson, Kirstin

    2013-08-01

    Most phase III clinical trials today are explanatory. Because explanatory, or efficacy, trials test hypotheses under "ideal" conditions, they are not well suited to providing guidance on decisions made in most clinical care contexts. Pragmatic trials, which test hypotheses under "usual" conditions, are often better suited to this task. Yet, pragmatic, or effectiveness, trials are infrequently carried out. This mismatch between the design of clinical trials and the needs of health care professionals is frustrating for everyone involved, and explains some of the challenges inherent in attempts to enhance knowledge translation and encourage evidence-based practice. The situation is more than simply frustrating, however; it is potentially unethical. Clinical trials must be socially valuable in order to (1) warrant the risks they impose on human research subjects and (2) fairly and efficiently assess new clinical interventions. Most bioethicists would agree that trials that have no social value, for instance, because their results do not have the potential to advance clinical care, should not be performed. What is less widely appreciated is that given limited research resources, trials that are more socially valuable should be preferred to trials that are less socially valuable when all else is equal. With respect to clinical trial design, I argue that while explanatory trials often have some social value, many have less social value than their pragmatic counterparts. On the basis of this general ethical assessment, I provide a preliminary defense of the position that clinical researchers should aim to conduct pragmatic trials, that is, that researchers face a burden of justification related to any idealizing elements added to trial designs.

  4. Sponsorship and design characteristics of trials registered in ClinicalTrials.gov.

    PubMed

    Roumiantseva, Dina; Carini, Simona; Sim, Ida; Wagner, Todd H

    2013-03-01

    We examine the extent to which ClinicalTrials.gov is meeting its goal of providing oversight and transparency of clinical trials with human subjects. We analyzed the ClinicalTrials.gov database contents as of June 2011, comparing interventions, medical conditions, and trial characteristics by sponsor type. We also conducted a detailed analysis of incomplete data. Among trials with only government sponsorship (N=9252), 36% were observational and 64% interventional; in contrast, almost all (90%) industry-only sponsored trials were interventional. Industry-only sponsored interventional trials (N=30,036) were most likely to report a drug intervention (81%), followed by biologics (9%) and devices (8%). Government-only interventional trials (N=5886) were significantly more likely to test behavioral interventions (28%) and procedures (13%) than industry-only trials (p<0.001). Medical conditions most frequently studied in industry-only trials were cancer (19%), cardiovascular conditions (12%) and endocrine/metabolic disorders (11%). Government-only funded trials were more likely to study mental health (19% vs. 7% for industry, p<.001), and viral infections, including HIV (15% vs 7% for industry, p<.001). Government-funded studies are significantly more likely to be missing data about study design and intervention arms in the registry. For all studies, we report ambiguous and contradictory data entries. Industry-sponsored studies differ systematically from government-sponsored studies in study type, choice of interventions, conditions studied, and completeness of submitted information. Imprecise study design information, incomplete coding of conditions, out-of-date or unspecified enrollment numbers, and other missing data continue to hinder robust analyses of trials registered in ClinicalTrials.gov. Published by Elsevier Inc.

  5. From ClinicalTrials.gov trial registry to an analysis-ready database of clinical trial results.

    PubMed

    Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

    2013-04-01

    The ClinicalTrials.gov web site provides a convenient interface to look up study results, but it does not allow downloading data in a format that can be readily used for quantitative analyses. To develop a system that automatically downloads study results from ClinicalTrials.gov and provides an interface to retrieve study results in a spreadsheet format ready for analysis. Sherlock(®) identifies studies by intervention, population, or outcome of interest and in seconds creates an analytic database of study results ready for analyses. The outcome classification algorithms used in Sherlock were validated against a classification by an expert. Having a database ready for analysis that can be updated automatically, dramatically extends the utility of the ClinicalTrials.gov trial registry. It increases the speed of comparative research, reduces the need for manual extraction of data, and permits answering a vast array of questions.

  6. Risk of selection bias in randomised trials.

    PubMed

    Kahan, Brennan C; Rehal, Sunita; Cro, Suzie

    2015-09-10

    Selection bias occurs when recruiters selectively enrol patients into the trial based on what the next treatment allocation is likely to be. This can occur even if appropriate allocation concealment is used if recruiters can guess the next treatment assignment with some degree of accuracy. This typically occurs in unblinded trials when restricted randomisation is implemented to force the number of patients in each arm or within each centre to be the same. Several methods to reduce the risk of selection bias have been suggested; however, it is unclear how often these techniques are used in practice. We performed a review of published trials which were not blinded to assess whether they utilised methods for reducing the risk of selection bias. We assessed the following techniques: (a) blinding of recruiters; (b) use of simple randomisation; (c) avoidance of stratification by site when restricted randomisation is used; (d) avoidance of permuted blocks if stratification by site is used; and (e) incorporation of prognostic covariates into the randomisation procedure when restricted randomisation is used. We included parallel group, individually randomised phase III trials published in four general medical journals (BMJ, Journal of the American Medical Association, The Lancet, and New England Journal of Medicine) in 2010. We identified 152 eligible trials. Most trials (98%) provided no information on whether recruiters were blind to previous treatment allocations. Only 3% of trials used simple randomisation; 63% used some form of restricted randomisation, and 35% did not state the method of randomisation. Overall, 44% of trials were stratified by site of recruitment; 27% were not, and 29% did not report this information. Most trials that did stratify by site of recruitment used permuted blocks (58%), and only 15% reported using random block sizes. Many trials that used restricted randomisation also included prognostic covariates in the randomisation procedure (56%). The

  7. Juvenile offenders: competence to stand trial.

    PubMed

    Soulier, Matthew

    2012-12-01

    This article details the legal background and assists the reader in the preparation and practical conduct of evaluations regarding juvenile adjudicative competency. The material is presented to be useful as a guide to direct questions of competency and covers aspects of evaluation that include: legal standard for competency to stand trial, developmental immaturity, current practice in juvenile competency to stand trial, forensic evaluation of juvenile competency to stand trial, organizing the evaluation, collateral sources of information, psychiatric evaluation of juvenile adjudicative competency, assessment of mental disorder and intellectual disability, assessment of developmental status, assessment of functional abilities for adjudicative competence, and reaching the forensic opinion.

  8. Randomized Clinical Trials in Localized Anal Cancer.

    PubMed

    Smith, Clayton A; Kachnic, Lisa A

    2017-10-01

    Management of anal carcinoma began as abdominoperineal resection and has evolved to combined chemotherapy and radiation. Early randomized trials demonstrated superior clinical outcomes of combined modality therapy over radiotherapy alone. Subsequent trials investigated alterations in the standard backbone of radiotherapy concurrent with 5-fluorouracil and mitomycin C with intent to maintain clinical outcomes while reducing treatment-related morbidity. The addition of intensity-modulated radiotherapy to radiation planning and delivery has subsequently reduced acute toxicity and detrimental treatment breaks. Ongoing and future trials are aimed at reducing therapy in favorable patient populations to decrease morbidity while intensifying treatment in patients with negative prognostic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Allocation Rules for Sequential Clinical Trials.

    DTIC Science & Technology

    1982-07-01

    AD-AIN 354 STANFORD UNIV CA DEPT OF STATISTICS F/V 12/1 ALLOCATION RULES FOR SEQUENTIAL CLINICAL TRIALS .(U) JUL 82 D SIEGMUND N00V11577-C-V306...UNCLASSIFIED TR 18 NL ALLOCATION RULES FOR SEQUENTIAL CLINICAL TRIALS BY D. SIEGMUND TECHNICAL REPORT NO. 18 JULY 1982 PREPARED UNDER CONTRACT N00014-77-C...at all. Rere me. discuss (I) and (11) or mes"s 9f a Monte Carlo experiment. The advantages of randomization in clinical trials has been discussed at

  10. A primer on clinical trial design.

    PubMed

    Ellimoottil, Chad; Vijan, Sandeep; Flanigan, Robert C

    2015-03-01

    A well-designed and executed clinical trial is the gold standard of evidence-based medicine. It is important for readers to understand the rationale for the study design, identify common pitfalls, and scrutinize limitations. Herein, we present a brief overview of types of designs used for clinical trials and discuss the use of appropriate end points, the selection of study participants, randomization, sample size calculation, blinding, and analysis of data. Finally, we emphasize the importance of accurate and transparent reporting. Our goal is to provide a primer for practicing urologists to enhance their understanding of the clinical trial literature.

  11. Major Trials | Division of Cancer Prevention

    Cancer.gov

    The studies listed below represent the first major clinical trials to evaluate risk reduction for people at high risk of breast, prostate, lung, colorectal, ovarian, cervical, and lung cancer. Analysis of the data gathered from these large trials continues to contribute valuable understanding about related issues, including screening, patient-reported symptoms, quality of life, nutrient impact, population/ethnicity differences, study design and implementation, and many others.  | Information on landmark clinical trials that evaluated cancer prevention interventions and cancer screening tests.

  12. RECENT CLINICAL TRIALS IN LUPUS NEPHRITIS

    PubMed Central

    Ward, Michael M.

    2014-01-01

    SYNOPSIS Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that mycophenolate mofetil may be similar to quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil. PMID:25034160

  13. Disease-mongering through clinical trials.

    PubMed

    González-Moreno, María; Saborido, Cristian; Teira, David

    2015-06-01

    Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple.

  14. Clinical trial design in feedlots.

    PubMed

    Perino, L J; Apley, M D

    1998-07-01

    As mentioned at the outset, the ultimate test of a product or procedure must be under field conditions and is best obtained from controlled studies of field use. Economic justification for use is based on this information. Each producer places a different value on attributable benefits such as improved health or growth performance. These values also change with fluctuating market values of cattle and feed. This makes determining the cost-benefit ratio of any procedure or product a moving target. Addressing this issue requires the clinically relevant and statistically significant differences that practitioners should be able to generate if they follow the guidelines presented here. There already exists a number of unusable studies. We suggest that those interested in undertaking this challenge be uncompromising in their experimental design. To be reliable, studies must follow the recommendations outlined above. Without sound field trial design and execution which ensures that the information is reliable and statistical significance which ensures that the differences are real, clinical outcomes cannot be extrapolated to economic justification. Any other course leads to making less than optimal recommendations on product use because of a lack of clinically relevant information.

  15. Recruitment to randomised trials: strategies for trial enrollment and participation study. The STEPS study.

    PubMed

    Campbell, M K; Snowdon, C; Francis, D; Elbourne, D; McDonald, A M; Knight, R; Entwistle, V; Garcia, J; Roberts, I; Grant, A; Grant, A

    2007-11-01

    To identify factors associated with good and poor recruitment to multicentre trials. Part A: database of trials started in or after 1994 and were due to end before 2003 held by the Medical Research Council and Health Technology Assessment Programmes. Part B: interviews with people playing a wide range of roles within four trials that their funders identified as 'exemplars'. Part C: a large multicentre trial (the CRASH trial) of treatment for head injury. The study used a number of different perspectives ('multiple lenses'), and three components. Part A: an epidemiological review of a cohort of trials. Part B: case studies of trials that appeared to have particularly interesting lessons for recruitment. Part C: a single, in-depth case study to examine the feasibility of applying a business-orientated analytical framework as a reference model in future trials. In the 114 trials found in Part A, less than one-third recruited their original target within the time originally specified, and around one-third had extensions. Factors observed more often in trials that recruited successfully were: having a dedicated trial manager, being a cancer or drug trial, and having interventions only available inside the trial. The most commonly reported strategies to improve recruitment were newsletters and mailshots, but it was not possible to assess whether they were causally linked to changes in recruitment. The analyses in Part B suggested that successful trials were those addressing clinically important questions at a timely point. The investigators were held in high esteem by the interviewees, and the trials were firmly grounded in existing clinical practices, so that the trial processes were not alien to clinical collaborators, and the results could be easily applicable to future practice. The interviewees considered that the needs of patients were well served by participation in the trials. Clinical collaborators particularly appreciated clear delineation of roles, which

  16. Patient-centeredness in the design of clinical trials.

    PubMed

    Mullins, C Daniel; Vandigo, Joseph; Zheng, Zhiyuan; Wicks, Paul

    2014-06-01

    Evidence from clinical trials should contribute to informed decision making and a learning health care system. People frequently, however, find participating in clinical trials meaningless or disempowering. Moreover, people often do not incorporate trial results directly into their decision making. The lack of patient centeredness in clinical trials may be partially addressed through trial design. For example, Bayesian adaptive trials designed to adjust in a prespecified manner to changes in clinical practice could motivate people and their health care providers to view clinical trials as more applicable to real-world clinical decisions. The way in which clinical trials are designed can transform the evidence generation process to be more patient centered, providing people with an incentive to participate or continue participating in clinical trials. To achieve the transformation to patient-centeredness in clinical trial decisions, however, there is a need for transparent and reliable methods and education of trial investigators and site personnel.

  17. Patient-centeredness in the design of clinical trials

    PubMed Central

    Mullins, C. Daniel; Vandigo, Joseph E.; Zheng, Jason; Wicks, Paul

    2014-01-01

    Evidence from clinical trials should contribute to informed decision making and a learning health care system. People frequently, however, find participating in clinical trials meaningless or disempowering. Moreover, people often do not incorporate trial results directly into their decision making. The lack of patient centeredness in clinical trials may be partially addressed through trial design. For example, Bayesian adaptive trials designed to adjust in a pre-specified manner to changes in clinical practice could motivate people and their health care providers to view clinical trials as more applicable to real-world clinical decisions. The way in which clinical trials are designed can transform the evidence generation process to be more patient centered, providing people with an incentive to participate or continue participating in clinical trials. In order to achieve the transformation to patient-centeredness in clinical trial decisions, however, there is a need for transparent and reliable methods and education of trial investigators and site personnel. PMID:24969009

  18. A method of extracting the number of trial participants from abstracts describing randomized controlled trials.

    PubMed

    Hansen, Marie J; Rasmussen, Nana Ø; Chung, Grace

    2008-01-01

    We have developed a method for extracting the number of trial participants from abstracts describing randomized controlled trials (RCTs); the number of trial participants may be an indication of the reliability of the trial. The method depends on statistical natural language processing. The number of interest was determined by a binary supervised classification based on a support vector machine algorithm. The method was trialled on 223 abstracts in which the number of trial participants was identified manually to act as a gold standard. Automatic extraction resulted in 2 false-positive and 19 false-negative classifications. The algorithm was capable of extracting the number of trial participants with an accuracy of 97% and an F-measure of 0.84. The algorithm may improve the selection of relevant articles in regard to question-answering, and hence may assist in decision-making.

  19. Clinical trials and SCID row: the ethics of phase 1 trials in the developing world.

    PubMed

    Kimmelman, Jonathan

    2007-12-01

    Relatively little has been written about the ethics of conducting early phase clinical trials involving subjects from the developing world. Below, I analyze ethical issues surrounding one of gene transfer's most widely praised studies conducted to date: in this study, Italian investigators recruited two subjects from the developing world who were ineligible for standard of care because of economic considerations. Though the study seems to have rendered a cure in these two subjects, it does not appear to have complied with various international guidelines that require that clinical trials conducted in the developing world be responsive to their populations' health needs. Nevertheless, policies devised to address large scale, late stage trials, such as the AZT short-course placebo trials, map somewhat awkwardly to early phase studies. I argue that interest in conducting translational research in the developing world, particularly in the context of hemophilia trials, should motivate more rigorous ethical thinking around clinical trials involving economically disadvantaged populations.

  20. Phase I (first-in-man) prophylactic vaccine's clinical trials: Selecting a clinical trial site

    PubMed Central

    Mehta, Shantanu; Goyal, Vishal; Singh, Kavita

    2015-01-01

    An appropriately equipped and staffed Phase I unit is critical for smooth conduct of a first-in-man clinical trial. The first-in-man prophylactic vaccine trial(s) requires basic infrastructure of clinical trial site, experienced and dedicated site staff and healthy adults as volunteers. The facility should have access to equipment, emergency services, laboratory, pharmacy and archiving. In terms of design, infrastructure, workflow and manpower, a Phase I unit for testing a novel vaccine or drug are quite similar. However, there are some important attributes, which should be taken into consideration, while performing pre-trial site selection for conducting phase I trial with a new or novel vaccine. PMID:25878951

  1. Optimizing operational efficiencies in early phase trials: the Pediatric Trials Network experience

    PubMed Central

    England, Amanda; Wade, Kelly; Smith, P. Brian; Berezny, Katherine; Laughon, Matthew

    2016-01-01

    Performing drug trials in pediatrics is challenging. In support of the Best Pharmaceuticals for Children Act, the Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the formation of the Pediatric Trials Network (PTN) in 2010. Since its inception, the PTN has developed strategies to increase both efficiency and safety of pediatric drug trials. Through use of innovative techniques such as sparse and scavenged blood sampling as well as opportunistic study design, participation in trials has grown. The PTN has also strived to improve consistency of adverse event reporting in neonatal drug trials through the development of a standardized adverse event table. We review how the PTN is optimizing operational efficiencies in pediatric drug trials to increase the safety of drugs in children. PMID:26968616

  2. Population activity changes during a trial-to-trial adaptation of bullfrog retinal ganglion cells.

    PubMed

    Ding, Wei; Xiao, Lei; Jing, Wei; Zhang, Pu-Ming; Liang, Pei-Ji

    2014-07-09

    A 'trial-to-trial adaptation' of bullfrog retinal ganglion cells in response to a repetitive light stimulus was investigated in the present study. Using the multielectrode recording technique, we studied the trial-to-trial adaptive properties of ganglion cells and explored the activity of population neurons during this adaptation process. It was found that the ganglion cells adapted with different degrees: their firing rates were decreased in different extents from early-adaptation to late-adaptation stage, and this was accompanied by a decrease in cross-correlation strength. In addition, adaptation behavior was different for ON-response and OFF-response, which implied that the mechanism of the trial-to-trial adaptation might involve bipolar cells and/or their synapses with other neurons and the stronger adaptation in the ganglion cells' OFF-responses might reflect the requirement to avoid possible saturation in the OFF circuit.

  3. Nutrition Intervention Trials in Linxian, China

    Cancer.gov

    Randomized controlled trials were launched in 1985 to test the effects of multiple vitamin and mineral interventions on total mortality and total and cause-specific cancer mortality in a rural Chinese population

  4. Southern California trial plantings of Eucalyptus

    Treesearch

    Paul W. Moore

    1983-01-01

    A trial planting to compare the biomass production of 9 tree species was established in May 1979. Species compared were Acacia melanoxylon, Casuarina cunninghamiana, Casuarina equisitifolia, Eucalyptus camaldulensis, E. dalrympleana, E...

  5. Swiss regulations for controlling clinical trials.

    PubMed

    Zanini, G M

    1998-04-01

    Switzerland has recently issued regulations designed to control all trials with drugs in human subjects, namely the 'Regolamento dell'Ufficio Intercantonale per il controllo dei medicamenti in fase di studio clinico' (Intercantonal Regulations Controlling Drugs used in Clinical Trials), which have been operating since 1st January 1995. These new regulations are generally consistent with other international regulations and have introduced the concept of good clinical practice (GCP) into Switzerland. There are other regulations in Switzerland, such as Federal regulations on immunobiological products, special rules governing the administration of radiolabelled drugs to humans, drugs of abuse and medical devices. Any gap in the central regulations must be filled by cantonal regulations, where they exist. This is a comprehensive review of the regulations governing clinical trials in Switzerland, with special attention being devoted to trials with therapeutic compounds and to compatibility between Swiss and international procedures.

  6. [Clinical trials. Some general ethical questions].

    PubMed

    Melo, J A

    1999-01-01

    This article provides an overview of the main problems that ethics committees deal with when analysing clinical trials. Some characteristics of the different phases are discussed as well as some particular problems of the Portuguese law.

  7. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research.

  8. Involving South Asian patients in clinical trials.

    PubMed

    Hussain-Gambles, M; Leese, B; Atkin, K; Brown, J; Mason, S; Tovey, P

    2004-10-01

    To investigate how South Asian patients conceptualise the notion of clinical trials and to identify key processes that impact on trial participation and the extent to which communication difficulties, perceptions of risk and attitudes to authority influence these decisions. Also to identify whether 'South Asian' patients are homogeneous in these issues, and which factors differ between different South Asian subgroups and finally how professionals regard the involvement of South Asian patients and their views on strategies to increase participation. A review of the literature on minority ethnic participation in clinical trials was followed by three qualitative interview studies. Interviews were taped and transcribed (and translated if required) and subjected to framework analysis. Face-to-face interviews were conducted with 25 health professionals; 60 South Asian lay people who had not taken part in a trial and 15 South Asian trial participants. Motivations for trial participation were identified as follows: to help society, to improve own health or that of family and friends, out of obligation to the doctor and to increase scientific knowledge. Deterrents were concerns about drug side-effects, busy lifestyles, language, previous bad experiences, mistrust and feelings of not belonging to British society. There was no evidence of antipathy amongst South Asians to the concept of clinical trials and, overall, the younger respondents were more knowledgeable than the older ones. Problems are more likely to be associated with service delivery. Lack of being approached was a common response. Lay-reported factors that might affect South Asian participation in clinical trials include age, language, social class, feeling of not belonging/mistrust, culture and religion. Awareness of clinical trials varied between each group. There are more similarities than differences in attitudes towards clinical trial participation between the South Asian and the general population

  9. Improving vaccine trials in infectious disease emergencies.

    PubMed

    Lipsitch, Marc; Eyal, Nir

    2017-07-14

    Unprecedented global effort is under way to facilitate the testing of countermeasures in infectious disease emergencies. Better understanding of the various options for trial design is needed in advance of outbreaks, as is preliminary global agreement on the most suitable designs for the various scenarios. What would enhance the speed, validity, and ethics of clinical studies of such countermeasures? Focusing on studies of vaccine efficacy and effectiveness in emergencies, we highlight three needs: for formal randomized trials-even in most emergencies; for individually randomized trials-even in many emergencies; and for six areas of innovation in trial methodology. These needs should inform current updates of protocols and roadmaps. Copyright © 2017, American Association for the Advancement of Science.

  10. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  11. Monitoring clinical trials: a practical guide.

    PubMed

    Molloy, Síle F; Henley, Patricia

    2016-12-01

    This article describes the processes and procedures involved in planning, conducting and reporting monitoring activities for large Clinical Trials of Investigational Medicinal Products (CTIMPs), focusing on those conducted in resource-limited settings. © 2016 John Wiley & Sons Ltd.

  12. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  13. Practical Issues when Planning for Field Trials

    NASA Astrophysics Data System (ADS)

    Andersson, Susanne; Andersson, Anna-Lena

    This chapter is written from a test site leader perspective and describes the role of planning and timing of field trials when testing technical solutions, which could enable people with dementia to live a more independent life. The chapter is based on experiences from setting up the first and second field trials in the three test sites of the COGKNOW project. The intention is to point out some key issues that are important in preparation and planning of a field trial. The chapter addresses issues in the preparatory, the actual and the post-test phase of the field trial in order to help achieve a high level of success both from a general perspective and with a special focus on people with dementia.

  14. Ebola Vaccine Appears Very Effective in Trial

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_162715.html Ebola Vaccine Appears Very Effective in Trial Drug manufacturer says ... Dec. 23, 2016 (HealthDay News) -- An experimental Ebola vaccine was highly effective against the deadly virus in ...

  15. Active Clinical Trials for Personalized Medicine

    PubMed Central

    Minsker, Stanislav; Zhao, Ying-Qi; Cheng, Guang

    2016-01-01

    Individualized treatment rules (ITRs) tailor treatments according to individual patient characteristics. They can significantly improve patient care and are thus becoming increasingly popular. The data collected during randomized clinical trials are often used to estimate the optimal ITRs. However, these trials are generally expensive to run, and, moreover, they are not designed to efficiently estimate ITRs. In this article, we propose a cost-effective estimation method from an active learning perspective. In particular, our method recruits only the “most informative” patients (in terms of learning the optimal ITRs) from an ongoing clinical trial. Simulation studies and real-data examples show that our active clinical trial method significantly improves on competing methods. We derive risk bounds and show that they support these observed empirical advantages. Supplementary materials for this article are available online. PMID:28018014

  16. Randomised trials for the Fitbit generation.

    PubMed

    Dempsey, Walter; Liao, Peng; Klasnja, Pedja; Nahum-Shani, Inbal; Murphy, Susan A

    2015-12-01

    Data from activity trackers and mobile phones can be used to craft personalised health interventions. But measuring the efficacy of these "treatments" requires a rethink of the traditional randomised trial.

  17. Scientific Review in Cancer Clinical Trials

    Cancer.gov

    Scientific review ensures that studies are based on sound science, which contributes to the safety of clinical trial participants. Learn about the role of Institutional Review Boards (IRBs), Data and Safety Monitoring Boards (DSMBs), and government agenci

  18. Minority Representation in Migraine Treatment Trials.

    PubMed

    Robbins, Nathaniel M; Bernat, James L

    2017-03-01

    Minorities have historically been underrepresented in clinical research trials despite having comparatively poor health indicators. Recognizing the dual inequalities of increased disease burden and decreased research participation, the National Institute of Health (NIH) Revitalization Act of 1993 mandated the inclusion and reporting of women and minorities in NIH-funded research. While progress has been made in the subsequent decades, this underrepresentation of minorities in research trials persists and has been documented in multiple disciplines. However, the extent of adequate representation and reporting of minority inclusion in clinical trials for migraine remains unknown. In this systematic review and study, we review the literature examining the representation of women and minorities in migraine clinical research trials METHODS: First we searched PubMed for pertinent articles examining the inclusion of women and minorities in migraine clinical research trials. Second, we identified controlled-trials for migraine published since 2011 in major neurology, headache, and general medicine journals using the terms "migraine randomized controlled trial." We then reviewed the results manually and excluded pilot studies and those with fewer than 50 participants. We next determined (a) how frequently representation of minorities and women were reported in these major trials; (b) what factors correlated with reporting; and (c) whether women and minority inclusion comprised their ratios in the general population. We identified 128 relevant clinical trials, of which 36 met our inclusion criteria. All 36 trials (100%) reported gender frequency, and 25 of 36 (69.4%) reported ethnicity or race. Among all studies, women and Whites represented 84.2 and 82.9% of participants (mean), respectively. Studies conducted in the United States and funded by a private company were more likely to report race than studies conducted exclusively outside of the U.S. or with a public sponsor

  19. Trial design innovations: Clinical trials for treatment of neuropsychiatric symptoms in Alzheimer's Disease

    PubMed Central

    Zhong, K

    2015-01-01

    Neuropsychiatric symptoms are common in Alzheimer's disease (AD) and other neurodegenerative disorders. Recent progress has been made with clinical trials, advancing new therapies for psychosis in Parkinson's disease (PD), agitation in AD, and apathy in AD. Definitions have emerged for agitation and apathy in patients with cognitive impairment, facilitating recruitment of clinical trial populations. Progress in clinical trial design and the agents being assessed promise to advance therapies for disabling symptoms and improve quality of life for patients and caregivers. PMID:26206713

  20. Evaluating the Generalisability of Trial Results: Introducing a Centre- and Trial-Level Generalisability Index.

    PubMed

    Gheorghe, Adrian; Roberts, Tracy; Hemming, Karla; Calvert, Melanie

    2015-11-01

    Few randomised controlled trials (RCTs) recruit centres representatively, which may limit the external validity of trial results. The aim of this study was to propose a proof-of-concept method of assessing the generalisability of the clinical and cost-effectiveness findings of a given RCT. We developed a generalisability index (Gix), informed by centre-level characteristics, as a measure of centre and trial representativeness. The centre-level Gix quantifies how representative a centre is in relation to its jurisdiction, e.g. a country or health authority. The trial-level Gix quantifies how representative trial recruitment is in relation to clinical practice in the jurisdiction. Taking a real-world RCT as a case study and assuming trial-wide results to represent 'true jurisdiction values', we used simulation methods to recreate 5000 RCTs and investigate the relationship between trial representativeness, reflected by the standardised trial-Gix, and the deviation of simulated trial results from the 'true values'. The simulation study provides evidence that trial results (odds ratio for the primary outcome and incremental quality-adjusted life-years) were influenced by the representativeness of the sample of recruiting centres. Simulated RCTs with the closest results to the 'true values' were those whose recruitment closely mirrored the jurisdiction-wide context. Results appeared robust to six alternative specifications of the Gix. Our findings suggest that an unrepresentative selection of centres limits the external validity of trial results. The Gix may be a valuable tool to help facilitate rational selection of trial centres and ensure the generalisability of results at the jurisdiction level.

  1. Constructing common cohorts from trials with overlapping eligibility criteria: implications for comparing effect sizes between trials.

    PubMed

    Mount, David L; Feeney, Patricia; Fabricatore, Anthony N; Coday, Mace; Bahnson, Judy; Byington, Robert; Phelan, Suzanne; Wilmoth, Sharon; Knowler, William C; Hramiak, Irene; Osei, Kwame; Sweeney, Mary Ellen; Espeland, Mark A

    2009-10-01

    Comparing findings from separate trials is necessary to choose among treatment options, however differences among study cohorts may impede these comparisons. As a case study, to examine the overlap of study cohorts in two large randomized controlled clinical trials that assess interventions to reduce risk of major cardiovascular disease events in adults with type 2 diabetes in order to explore the feasibility of cross-trial comparisons The Action for Health in Diabetes (Look AHEAD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials enrolled 5145 and 10,251 adults with type 2 diabetes, respectively. Look AHEAD assesses the efficacy of an intensive lifestyle intervention designed to produce weight loss; ACCORD tests pharmacological therapies for control of glycemia, hyperlipidemia, and hypertension. Incidence of major cardiovascular disease events is the primary outcome for both trials. A sample was constructed to include participants from each trial who appeared to meet eligibility criteria and be appropriate candidates for the other trial's interventions. Demographic characteristics, health status, and outcomes of members and nonmembers of this constructed sample were compared. Nearly 80% of Look AHEAD participants were projected to be ineligible for ACCORD; ineligibility was primarily due to better glycemic control or no early history of cardiovascular disease. Approximately 30% of ACCORD participants were projected to be ineligible for Look AHEAD, often for reasons linked to poorer health. The characteristics of participants projected to be jointly eligible for both trials continued to reflect differences between trials according to factors likely linked to retention, adherence, and study outcomes. Accurate ascertainment of cross-trial eligibility was hampered by differences between protocols. Despite several similarities, the Look AHEAD and ACCORD cohorts represent distinct populations. Even within the subsets of participants who appear to

  2. Reporting clinical trial information: colorectal cancer trials at Sydney Cancer Centre.

    PubMed

    Chua, W; Horvath, L; Beale, P; Clarke, S J

    2012-04-01

    Clinical trial units are integral to the functioning of a medical oncology department with patient access to clinical trials an important component in patient care. There has been a paucity of potential key performance indicators in medical oncology and clinical trial information may be utilised for this purpose. The aim of this study was to record retrospectively and collate prospectively collected information regarding basic demographics, response rate, progression and survival plus grade 3 or 4 toxicity in patients enrolled in clinical trials for metastatic colorectal cancer at the Sydney Cancer Centre between 1999 and 2007. Baseline patient demographics, clinical response, progression dates, grade 3 or 4 toxicities plus treatment-related fatalities were collected from individual clinical trials. Outcome measures were clinical response, progression-free survival and overall survival. There was a total of 14 trials undertaken during the defined period for patients with metastatic colorectal cancer. There was available information for 243 patient trials with sufficient information regarding response rates, toxicity, progression and survival. Tumour response rates ranged from 27% to 66% for first line chemotherapy trials and 0% to 20% for non-first line chemotherapy trials. The overall progression-free survival was 6.4 months and overall survival 14.0 months for all trials. There was one treatment-related fatality on clinical trial during this period. Results of our clinical database have been used here to illustrate the concept and value of reporting clinical trial information in medical oncology. Public reporting of such information may allow for comparisons between units and for quality improvement. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  3. Trial design innovations: Clinical trials for treatment of neuropsychiatric symptoms in Alzheimer's Disease.

    PubMed

    Cummings, J; Zhong, K

    2015-11-01

    Neuropsychiatric symptoms are common in Alzheimer's disease (AD) and other neurodegenerative disorders. Recent progress has been made with clinical trials, advancing new therapies for psychosis in Parkinson's disease (PD), agitation in AD, and apathy in AD. Definitions have emerged for agitation and apathy in patients with cognitive impairment, facilitating recruitment of clinical trial populations. Progress in clinical trial design and the agents being assessed promise to advance therapies for disabling symptoms and improve quality of life for patients and caregivers.

  4. Razors versus clippers. A randomised controlled trial.

    PubMed

    Taylor, Tracy; Tanner, Judith

    2005-12-01

    The purpose of this randomised controlled trial was to determine if patients showed a preference for preoperative hair removal with razors or clippers and to identify if one method was associated with more trauma or postoperative infections. The trial took place in a day surgery unit with patients who were having a range of surgical procedures including hernias and varicose veins. This study was sponsored by an award from the NATN/3M Clinical Fellowship.

  5. Robust inference for group sequential trials.

    PubMed

    Ganju, Jitendra; Lin, Yunzhi; Zhou, Kefei

    2017-03-01

    For ethical reasons, group sequential trials were introduced to allow trials to stop early in the event of extreme results. Endpoints in such trials are usually mortality or irreversible morbidity. For a given endpoint, the norm is to use a single test statistic and to use that same statistic for each analysis. This approach is risky because the test statistic has to be specified before the study is unblinded, and there is loss in power if the assumptions that ensure optimality for each analysis are not met. To minimize the risk of moderate to substantial loss in power due to a suboptimal choice of a statistic, a robust method was developed for nonsequential trials. The concept is analogous to diversification of financial investments to minimize risk. The method is based on combining P values from multiple test statistics for formal inference while controlling the type I error rate at its designated value.This article evaluates the performance of 2 P value combining methods for group sequential trials. The emphasis is on time to event trials although results from less complex trials are also included. The gain or loss in power with the combination method relative to a single statistic is asymmetric in its favor. Depending on the power of each individual test, the combination method can give more power than any single test or give power that is closer to the test with the most power. The versatility of the method is that it can combine P values from different test statistics for analysis at different times. The robustness of results suggests that inference from group sequential trials can be strengthened with the use of combined tests. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Closeout of the HALT-PKD Trials

    PubMed Central

    Moore, Charity G.; Spillane, Susan; Simon, Gertrude; Maxwell, Barbara; Rahbari-Oskoui, Frederic F.; Braun, William E.; Chapman, Arlene B.; Schrier, Robert W.; Torres, Vicente E.; Perrone, Ronald D.; Steinman, Theodore I.; Brosnahan, Godela; Czarnecki, Peter G.; Harris, Peter C.; Miskulin, Dana C.; Flessner, Michael F.; Bae, K. Ty; Abebe, Kaleab Z.; Hogan, Marie C.

    2015-01-01

    Background The HALT Polycystic Kidney Disease Trials Network consisted of two randomized, double blind, placebo-controlled trials among patients with autosomal dominant polycystic kidney disease. The trials involved 5–8 years of participant follow-up with interventions in blood pressure and antihypertensive therapy. We provide a framework for designing and implementing closeout near the end of a trial while ensuring patient safety and maintaining scientific rigor and study morale. Methods We discuss issues and resolutions for determining the last visit, tapering medications, and unblinding of participants to study allocation and results. We also discuss closure of clinical sites and Data Coordinating Center responsibilities to ensure timely release of study results and meeting the requirements of regulatory and funding authorities. Results Just over 90% of full participants had a 6-month study visit prior to their last visit preparing them for trial closeout. Nearly all patients wanted notification of study results (99%) and treatment allocation (99%). All participants were safely tapered off study and open label blood pressure medications. Within 6 months, the trials were closed, primary papers published, and 805 letters distributed to participants with results and allocation. DCC obligations for data repository and clinicaltrials.gov reporting were completed within 12 months of the last study visit. Conclusions Closeout of our trials involved years of planning and significant human and financial resources. We provide questions for investigators to consider when planning closeout of their trials with focus on (1) patient safety (2) dissemination of study results and (3) compliance with regulatory and funding responsibilities. PMID:26231556

  7. Air Monitoring Trials on HMAS OVENS

    DTIC Science & Technology

    1996-06-01

    ABSTRACT (R) (R) Three air monitoring trials were undertaken in an RAN Oberon class submarine, HMAS Ovens, using an instrument package consisting of...Royal Australian Navy Oberon class submarines has always been a matter of concern amongst submariners and particular attention has been paid to this...instruments were connected to a datalogger and left unattended for 1- 2 week periods. The results showed that during the trial periods, with the exception of

  8. Nutraceuticals and atherosclerosis: human trials.

    PubMed

    Badimon, Lina; Vilahur, Gemma; Padro, Teresa

    2010-08-01

    The high prevalence of obesity, atherosclerosis, and cardiovascular disease (CVD) is largely attributable to the contemporary lifestyle that is often sedentary and includes a diet high in saturated fats and sugars and low ingestion polyunsaturated fatty acids (PUFAs), fruit, vegetables, and fiber. Epidemiological studies have confirmed a strong association between fat intake, especially saturated- and transfatty acids, plasma cholesterol levels, and rate of coronary heart disease (CHD) mortality. In counterpart, beneficial cardiovascular effects have been reported in populations consuming the "healthy" Mediterranean-type diet. Indeed, many nutrients and phytochemicals in fruits, vegetables, and wine, including fiber, vitamins, minerals, antioxidants, have shown to be independently or jointly responsible for the apparent reduction in CVD risk. Therefore, in patients with overt CVD, efforts have focused on combining both drug treatments and nutrition interventions. Undoubtedly, the advances in the knowledge of both the disease processes and healthy dietary components have provided new avenues to develop pharmaceutical and/or dietary strategies to halt the development of vascular disease. In this regard, within the last years, pioneering nutritional strategies, such as nutraceuticals, have been developed aimed at reducing the main atherosclerotic risk factors and promoting cardiovascular health. Furthermore, a growing body of clinical evidence has demonstrated positive cardiovascular effects associated with dietary fibers, cholesterol-lowering natural agents, olive oil, omega-3 PUFAs, antioxidants, and polyphenols intake. Moreover, monounsaturated fatty acids intake has shown to modulate the expression of key atherosclerotic-related genes. Yet, in the case of antioxidants, some large clinical trials have failed to confirm such atheroprotective effects. Furthermore, there might be interactions between these natural food supplements and cardiovascular medications that

  9. Mountain rescue stretchers: usability trial.

    PubMed

    Hignett, Sue; Willmott, Joseph Wayne; Clemes, Stacy

    2009-01-01

    In the UK mountain rescues are carried out by highly trained volunteers in all weather conditions and at any time of the day/night. They interface with other services when they hand over the casualty to either land or air ambulances. The design of the stretcher is important to the safety of both the volunteers and casualties. This paper reports a usability trial to evaluate the features of mountain rescue stretchers and identify characteristics for future design. Two mountain rescue teams in the English Lake District participated in a five week field experiment. Data were collected using postural analysis with Rapid Entire Body Analysis, Body Part Discomfort Surveys, Rated Perceived Exertion and focus groups to compare the performance of four stretchers: Split Thomas, Ferno Titan, MacInnes mark 6 and MacInnes mark 7. None of the stretchers had an overall advantage, with benefits for some features counterbalanced by disadvantages resulting from others. All the stretchers produced shoulder discomfort with the Split Thomas and MacInnes 6 lowering the postural risks through the use of skids/wheel in the carrying phase. The key design features for future MR stretchers include: reduced unloaded weight (e.g. light weight materials and mesh platforms); undercarriage system to reduce the carrying load; adjustable handles at the front and back positions; flexible carrying system with an optional harness attachment; ease of assembly in adverse environmental conditions; large carrying capacity. It is suggested that military emergency evacuation should be considered in addition to mountain rescue tasks to identify a larger commercial market for development.

  10. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable

    PubMed Central

    Julious, Steven A; Cooper, Cindy L; Campbell, Michael J

    2015-01-01

    Sample size justification is an important consideration when planning a clinical trial, not only for the main trial but also for any preliminary pilot trial. When the outcome is a continuous variable, the sample size calculation requires an accurate estimate of the standard deviation of the outcome measure. A pilot trial can be used to get an estimate of the standard deviation, which could then be used to anticipate what may be observed in the main trial. However, an important consideration is that pilot trials often estimate the standard deviation parameter imprecisely. This paper looks at how we can choose an external pilot trial sample size in order to minimise the sample size of the overall clinical trial programme, that is, the pilot and the main trial together. We produce a method of calculating the optimal solution to the required pilot trial sample size when the standardised effect size for the main trial is known. However, as it may not be possible to know the standardised effect size to be used prior to the pilot trial, approximate rules are also presented. For a main trial designed with 90% power and two-sided 5% significance, we recommend pilot trial sample sizes per treatment arm of 75, 25, 15 and 10 for standardised effect sizes that are extra small (≤0.1), small (0.2), medium (0.5) or large (0.8), respectively. PMID:26092476

  11. Qualitative research within trials: developing a standard operating procedure for a clinical trials unit

    PubMed Central

    2013-01-01

    Background Qualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design. Methods Health services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP). Results The qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component. Conclusions We recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials. PMID:23433341

  12. From international to zonal trials: the origins of the Nuremberg medical trial.

    PubMed

    Weindling, P

    2000-01-01

    This article examines how plans to have a second International Military Tribunal led to the Medical Trial at Nuremberg. While the British opposed a second international trial because of their distrust of the Soviets, they supported a plan for a series of special zonal trials to be conducted by the American authorities at Nuremberg. In December 1945 the British became aware of the extent of medical war crimes committed by the Germans. Their investigation led to an eventual handover to the Americans of a group of German doctors for trial at Nuremberg. At the same time the British and French Supported an International Scientific Commission for the Investigation of Medical War Crimes.

  13. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hip osteoarthritis.

    PubMed

    Lane, N E; Hochberg, M C; Nevitt, M C; Simon, L S; Nelson, A E; Doherty, M; Henrotin, Y; Herontin, Y; Flechsenhar, K

    2015-05-01

    The ability to assess the efficacy and effectiveness of an intervention for the treatment of hip osteoarthritis (OA) requires strong clinical trial methodology. This consensus paper provides recommendations based on a narrative literature review and best judgment of the members of the committee for clinical trials of hip OA. We provide recommendations on clinical trial design, outcome measures, including structural (radiography), and patient and physician global assessments, performance based measures, molecular markers and experimental endpoints including MRI imaging. This information can be utilized by sponsors of trials for new therapeutic agents for hip OA.

  14. Beyond trial-by-trial adaptation: A quantification of the time scale of cognitive control.

    PubMed

    Aben, Bart; Verguts, Tom; Van den Bussche, Eva

    2017-03-01

    The idea that adaptation to stimulus or response conflict can operate over different time scales takes a prominent position in various theories and models of cognitive control. The mechanisms underlying temporal variations in control are nevertheless poorly understood, which is partly due to a lack of appropriate empirical measures. Inspired by reinforcement learning models, we developed a method to quantify the time scale of control behaviorally, by computing trial-by-trial effects that go beyond the preceding trial. Briefly, we extended the congruency sequence effect from 1 trial to multiple trials into the past and quantified the influence of previous trials on current-trial performance as a function of trial distance. The rate at which this influence changes across trials was taken as a measure of the time scale of control. We applied the method to a flanker task with different conflict frequencies and volatility. Results showed that the time scale of control was smaller in rare-conflict and volatile contexts, compared to frequent-conflict and neutral contexts. This is in agreement with theories differentiating transient from sustained control. The method offers new opportunities to reveal temporal differences in control modes and can easily be applied to various empirical paradigms. (PsycINFO Database Record

  15. Qualitative research within trials: developing a standard operating procedure for a clinical trials unit.

    PubMed

    Rapport, Frances; Storey, Mel; Porter, Alison; Snooks, Helen; Jones, Kerina; Peconi, Julie; Sánchez, Antonio; Siebert, Stefan; Thorne, Kym; Clement, Clare; Russell, Ian

    2013-02-21

    Qualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design. Health services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP). The qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component. We recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials.

  16. Strategic physician communication and oncology clinical trials.

    PubMed

    Albrecht, T L; Blanchard, C; Ruckdeschel, J C; Coovert, M; Strongbow, R

    1999-10-01

    Clinical trials are the primary means for determining new, effective treatments for cancer patients, yet the number of patients that accrue is relatively limited. The purpose of this study was to explore the relationship between physician behavior and patient accrual to a clinical trial by videotaping the interaction. Forty-eight patient-physician interactions involving 12 different oncologists were videotaped in several clinics at the H. Lee Moffitt Cancer Center and Research Institute (Tampa, FL). The purpose of each interaction was to present the possibility of a clinical trial to the patient. A coding system, the Moffitt Accrual Analysis System, was developed by the authors to code behaviors that represented both the legal-informational and social influence models of communication behavior. Thirty-two patients agreed to participate in the clinical trial. Videotaping was found to be a viable, valid, and reliable method for studying the interaction. Physicians who were observed to use both models of influence were found to enroll more patients. Thus, patients were more likely to accrue to the trial when their physician verbally presented items normally included in an informed consent document and when they behaved in a reflective, patient-centered, supportive, and responsive manner. Discussion of benefits, side effects, patient concerns and resources to manage the concerns were all associated with accrual. This research has implications for modifying physician behavior and, thus, increasing the numbers of patients accruing to oncology clinical trials.

  17. Clinical trial networks in orthopaedic surgery.

    PubMed

    Rangan, A; Jefferson, L; Baker, P; Cook, L

    2014-05-01

    The aim of this study was to review the role of clinical trial networks in orthopaedic surgery. A total of two electronic databases (MEDLINE and EMBASE) were searched from inception to September 2013 with no language restrictions. Articles related to randomised controlled trials (RCTs), research networks and orthopaedic research, were identified and reviewed. The usefulness of trainee-led research collaborations is reported and our knowledge of current clinical trial infrastructure further supplements the review. Searching yielded 818 titles and abstracts, of which 12 were suitable for this review. Results are summarised and presented narratively under the following headings: 1) identifying clinically relevant research questions; 2) education and training; 3) conduct of multicentre RCTs and 4) dissemination and adoption of trial results. This review confirms growing international awareness of the important role research networks play in supporting trials in orthopaedic surgery. Multidisciplinary collaboration and adequate investment in trial infrastructure are crucial for successful delivery of RCTs. Cite this article: Bone Joint Res 2014;3:169-74. ©2014 The British Editorial Society of Bone & Joint Surgery.

  18. Randomized controlled trials - a matter of design.

    PubMed

    Spieth, Peter Markus; Kubasch, Anne Sophie; Penzlin, Ana Isabel; Illigens, Ben Min-Woo; Barlinn, Kristian; Siepmann, Timo

    2016-01-01

    Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial.

  19. Strategies and Endpoints of Antifibrotic Drug Trials

    PubMed Central

    Torok, Natalie; Dranoff, Jonathan A.; Schuppan, Detlef; Friedman, Scott L.

    2015-01-01

    There is an urgent need to develop antifibrotic therapies for chronic liver disease, and to clarify which endpoints in antifibrotic trials will be acceptable to regulatory agencies. AASLD sponsored an endpoints conference to help accelerate the efficient testing of antifibrotic agents and to develop recommendations on clinical trial design for liver fibrosis. In this review we summarize the salient and novel elements of this conference and provide directions for future clinical trial design. The paper follows the structure of the conference and is organized into five areas: I) Antifibrotic trial design; II) Preclinical proof of concept studies; III) Pharmacologic targets: rationale and lessons to learn; IV) Rational drug design and development; V) Consensus and recommendations on design of clinical trials in liver fibrosis. Expert overviews and collaborative discussions helped to summarize the key unmet needs and directions for the future, including: 1) Greater clarification of at-risk populations and study groups; 2) Standardization of all elements of drug discovery and testing; 3) Standardization of clinical trial approaches; 4) Accelerated development of improved non-invasive markers; 5) Need for exploration of potential off-target toxicities of future antifibrotic drugs. PMID:25626988

  20. Developing antitussives: the ideal clinical trial.

    PubMed

    Birring, Surinder S

    2009-04-01

    Antitussive drugs are amongst the most widely used medications worldwide; however no new class of drugs have been introduced into the market for many years. Trials showing patient benefit are scarce and have been hampered by the lack of objective and validated outcome measures. Recent improvements in the assessment of cough will facilitate better trials and aid the development of antitussive drugs. When conducting a trial, patient selection is of paramount importance. Patients with unexplained chronic cough and sub-acute cough following upper respiratory tract infection are ideal because they represent an unmet clinical need and an untapped market for pharmaceutical companies. Patients with asthma and chronic obstructive pulmonary disease are less suitable since cough suppression is not always desirable and the findings of trials may not be generalisable to all patients with cough. Randomized, placebo-controlled, double-blind clinical trials are obviously the gold standard. The choice of placebo, whether inert or active, depends on the incidence and severity of drug side-effects. The primary outcome measure should be objective and cough monitors are the ideal tool. Subjective outcome measures should be used to assess symptoms and health related quality of life. Properly conducted clinical trials are an opportunity to evaluate the benefits of currently available therapies and aid advances in the antitussive drug market.

  1. Parallel multicentre randomised trial of a clinical trial question prompt list in patients considering participation in phase 3 cancer treatment trials

    PubMed Central

    Tattersall, Martin H N; Jefford, Michael; Martin, Andrew; Olver, Ian; Thompson, John F; Brown, Richard F; Butow, Phyllis N

    2017-01-01

    Objective To evaluate the effect of a clinical trial question prompt list in patients considering enrolment in cancer treatment trials. Setting Tertiary cancer referral hospitals in three state capital cities in Australia. Participants 88 patients with cancer attending three cancer centres in Australia, who were considering enrolment in phase 3 treatment trials, were invited to enrol in an unblinded randomised trial of provision of a clinical trial question prompt list (QPL) before consenting to enrol in the treatment trial. Interventions We developed and pilot tested a targeted QPL for patients with cancer considering clinical trial participation (the clinical trial QPL). Consenting patients were randomised to receive the clinical trial QPL or not before further discussion with their oncologist and/or trial nurse about the treatment trial. Primary and secondary outcomes Questionnaires were completed at baseline and within 3 weeks of deciding on treatment trial participation. Main outcome measure: scores on the Quality of Informed Consent questionnaire (QuIC). Results 88 patients of 130 sought for the study were enrolled (43 males), and 45 received the clinical trial QPL. 49% of trials were chemotherapy interventions for patients with advanced disease, 35% and 16% were surgical adjuvant and radiation adjuvant trials respectively. 70 patients completed all relevant questionnaires. 28 of 43 patients in the control arm compared with 39 of 45 patients receiving the clinical trial QPL completed the QuIC (p=0.0124). There were no significant differences in the QuIC scores between the randomised groups (QuIC part A p=0.08 and QuIC part B p=0.92). There were no differences in patient satisfaction with decisions or in anxiety levels between the randomised groups. Conclusions Use of a question prompt list did not significantly change the QuIC scores in this randomised trial. ANZCTR 12606000214538 prospectively registered 31/5/2006. Trial registration number Results, ACTRN

  2. 21 CFR 886.1415 - Ophthalmic trial lens frame.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ophthalmic trial lens frame. 886.1415 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1415 Ophthalmic trial lens frame. (a) Identification. An opthalmic trial lens frame is a mechanical device intended to hold trial lenses for...

  3. 21 CFR 886.1415 - Ophthalmic trial lens frame.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ophthalmic trial lens frame. 886.1415 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1415 Ophthalmic trial lens frame. (a) Identification. An opthalmic trial lens frame is a mechanical device intended to hold trial lenses for...

  4. 21 CFR 886.1415 - Ophthalmic trial lens frame.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ophthalmic trial lens frame. 886.1415 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1415 Ophthalmic trial lens frame. (a) Identification. An opthalmic trial lens frame is a mechanical device intended to hold trial lenses for...

  5. 21 CFR 886.1415 - Ophthalmic trial lens frame.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ophthalmic trial lens frame. 886.1415 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1415 Ophthalmic trial lens frame. (a) Identification. An opthalmic trial lens frame is a mechanical device intended to hold trial lenses for...

  6. 42 CFR 460.190 - Monitoring during trial period.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Monitoring during trial period. 460.190 Section 460... ELDERLY (PACE) Federal/State Monitoring § 460.190 Monitoring during trial period. (a) Trial period review. During the trial period, CMS, in cooperation with the State administering agency, conducts comprehensive...

  7. 42 CFR 460.190 - Monitoring during trial period.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Monitoring during trial period. 460.190 Section 460... ELDERLY (PACE) Federal/State Monitoring § 460.190 Monitoring during trial period. (a) Trial period review. During the trial period, CMS, in cooperation with the State administering agency, conducts comprehensive...

  8. 47 CFR 5.601 - Product development trials.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Product development trials. 5.601 Section 5.601... Market Trials § 5.601 Product development trials. Unless otherwise stated in the instrument of authorization, experimental radio licenses granted for the purpose of product development trials pursuant to § 5...

  9. 42 CFR 460.190 - Monitoring during trial period.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Monitoring during trial period. 460.190 Section 460... ELDERLY (PACE) Federal/State Monitoring § 460.190 Monitoring during trial period. (a) Trial period review. During the trial period, CMS, in cooperation with the State administering agency, conducts comprehensive...

  10. 47 CFR 5.601 - Product development trials.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Product development trials. 5.601 Section 5.601... Market Trials § 5.601 Product development trials. Unless otherwise stated in the instrument of authorization, experimental radio licenses granted for the purpose of product development trials pursuant to § 5...

  11. 42 CFR 460.190 - Monitoring during trial period.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Monitoring during trial period. 460.190 Section 460... ELDERLY (PACE) Federal/State Monitoring § 460.190 Monitoring during trial period. (a) Trial period review. During the trial period, CMS, in cooperation with the State administering agency, conducts comprehensive...

  12. 42 CFR 460.190 - Monitoring during trial period.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Monitoring during trial period. 460.190 Section 460... ELDERLY (PACE) Federal/State Monitoring § 460.190 Monitoring during trial period. (a) Trial period review. During the trial period, CMS, in cooperation with the State administering agency, conducts comprehensive...

  13. The International "Trial of the 20th Century": Nuremberg.

    ERIC Educational Resources Information Center

    Chemerinsky, Erwin

    1999-01-01

    Considers the Nuremberg trials to be the "Trial of the Century." Highlights the series of 13 trials in which Nazi leaders, officials, judges, and others were tried, and most convicted, for war crimes. Relates that these trials had far-reaching effects in that they showed that moral obligations transcend national boundaries. (CMK)

  14. A Comparison of Randomised Controlled Trials in Health and Education

    ERIC Educational Resources Information Center

    Torgerson, Carole J.; Torgerson, David J.; Birks, Yvonne F.; Porthouse, Jill

    2005-01-01

    Health care and educational trials face similar methodological challenges. Methodological reviews of health care trials have shown that a significant proportion have methodological flaws. Whether or not educational trials have a similar proportion of poor-quality trials is unknown. The authors undertook a methodological comparison between health…

  15. 20 CFR 404.1592 - The trial work period.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the trial work period in determining whether your disability ended at any time after the trial work... that your disability has ended at any time during the trial work period if the medical or other... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false The trial work period. 404.1592 Section 404...

  16. 21 CFR 886.1415 - Ophthalmic trial lens frame.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic trial lens frame. 886.1415 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1415 Ophthalmic trial lens frame. (a) Identification. An opthalmic trial lens frame is a mechanical device intended to hold trial lenses for...

  17. Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

    PubMed Central

    Wiljer, David; Cafazzo, Joseph A

    2016-01-01

    Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study

  18. UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

    PubMed Central

    2012-01-01

    Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by

  19. Accessibility of trial reports for drugs stalling in development: a systematic assessment of registered trials.

    PubMed

    Hakala, Amanda; Kimmelman, Jonathan; Carlisle, Benjamin; Freeman, Georgina; Fergusson, Dean

    2015-03-09

    To quantify the proportion of trials for unsuccessfully licensed drugs that are not published. A systematic assessment of the availability of published research reports for publicly registered trials testing drugs stalling in clinical development ("stalled drugs") and drugs receiving regulatory licensure in the same time period ("licensed drugs"). Searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, and electronic query of contacts in registries to identify trials and assess publication status. The cohort of licensed drugs consisted of all disease modifying drugs in cancer, cardiovascular disease, or neurological disorders that received Food and Drug Administration licensure during 2005 to 2009 inclusive. The cohort of stalled drugs included unlicensed drugs in the same disease areas that had at least one completed phase III trial before 2009 and no evidence of any clinical trial activity after 31 December 2009. Inclusion criteria for registered trials advanced into publication searching were an intervention tested in a disease modifying, phase II, III, or IV trial registered on clinicaltrials.gov, with enrolment of at least one patient, that reported primary outcome collection end date between 1 January 2006 and 31 December 2008. The unadjusted publication proportion for registered trials of licensed drugs was 75% (72/96) versus 37% (30/81) for stalled drugs. The adjusted hazard ratio for publication was 2.7 (95% confidence interval 1.7 to 4.3) in favour of licensed drug trials. Higher publication rates for licensed drug trials were observed regardless of disease type, sponsorship, trial phase, and geography. The rate of non-publication of stalled drug trials was significantly higher for studies that did not complete enrolment compared with licensed drug trials. A total of 20,135 patients participated in trials of stalled drugs that were never published. Much of the information collected in unsuccessful drug trials is inaccessible to the broader

  20. Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database.

    PubMed

    Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina

    2016-03-22

    To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future.

  1. An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

    PubMed

    Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

    2013-11-01

    To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

  2. An Analysis of Registered Clinical Trials in Otolaryngology from 2007 to 2010: ClinicalTrials.gov

    PubMed Central

    Witsell, David L.; Schulz, Kristine A.; Lee, Walter T.; Chiswell, Karen

    2014-01-01

    Objective To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Study Design Database analysis. Setting Trial registration data downloaded from Clinical Trials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Methods Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. Results A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Conclusions Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field. PMID:24107478

  3. Making clinical trials more relevant: improving and validating the PRECIS tool for matching trial design decisions to trial purpose.

    PubMed

    Loudon, Kirsty; Zwarenstein, Merrick; Sullivan, Frank; Donnan, Peter; Treweek, Shaun

    2013-04-27

    If you want to know which of two or more healthcare interventions is most effective, the randomised controlled trial is the design of choice. Randomisation, however, does not itself promote the applicability of the results to situations other than the one in which the trial was done. A tool published in 2009, PRECIS (PRagmatic Explanatory Continuum Indicator Summaries) aimed to help trialists design trials that produced results matched to the aim of the trial, be that supporting clinical decision-making, or increasing knowledge of how an intervention works. Though generally positive, groups evaluating the tool have also found weaknesses, mainly that its inter-rater reliability is not clear, that it needs a scoring system and that some new domains might be needed. The aim of the study is to: Produce an improved and validated version of the PRECIS tool. Use this tool to compare the internal validity of, and effect estimates from, a set of explanatory and pragmatic trials matched by intervention. The study has four phases. Phase 1 involves brainstorming and a two-round Delphi survey of authors who cited PRECIS. In Phase 2, the Delphi results will then be discussed and alternative versions of PRECIS-2 developed and user-tested by experienced trialists. Phase 3 will evaluate the validity and reliability of the most promising PRECIS-2 candidate using a sample of 15 to 20 trials rated by 15 international trialists. We will assess inter-rater reliability, and raters' subjective global ratings of pragmatism compared to PRECIS-2 to assess convergent and face validity. Phase 4, to determine if pragmatic trials sacrifice internal validity in order to achieve applicability, will compare the internal validity and effect estimates of matched explanatory and pragmatic trials of the same intervention, condition and participants. Effect sizes for the trials will then be compared in a meta-regression. The Cochrane Risk of Bias scores will be compared with the PRECIS-2 scores of

  4. Linking ClinicalTrials.gov and PubMed to Track Results of Interventional Human Clinical Trials

    PubMed Central

    Huser, Vojtech; Cimino, James J.

    2013-01-01

    Objective In an effort to understand how results of human clinical trials are made public, we analyze a large set of clinical trials registered at ClinicalTrials.gov, the world’s largest clinical trial registry. Materials and Methods We considered two trial result artifacts: (1) existence of a trial result journal article that is formally linked to a registered trial or (2) the deposition of a trial’s basic summary results within the registry. Results The study sample consisted of 8907 completed, interventional, phase 2-or-higher clinical trials that were completed in 2006-2009. The majority of trials (72.2%) had no structured trial-article link present. Atotal of 2367 trials (26.6%) deposited basic summary results within the registry. Ofthose, 969 trials (10.9%) were classified as trials with extended results and 1398 trials (15.7%) were classified as trials with only required basic results. The majority of the trials (54.8%) had no evidence of results, based on either linked result articles or basic summary results (silent trials), while a minimal number (9.2%) report results through both registry deposition and publication. Discussion Our study analyzes the body of linked knowledge around clinical trials (which we refer to as the “trialome”). Our results show that most trials do not report results and, for those that do, there is minimal overlap in the types of reporting. We identify several mechanisms by which the linkages between trials and their published results can be increased. Conclusion Our study shows that even when combining publications and registry results, and despite availability of several information channels, trial sponsors do not sufficiently meet the mandate to inform the public either via a linked result publication or basic results submission. PMID:23874614

  5. Internet trials: participant experiences and perspectives

    PubMed Central

    2012-01-01

    Background Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants’ attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. Objective To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. Methods All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. Results 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate). Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants’ comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience – a perceived benefit – and a lack connectedness and understanding – a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet; security, privacy and

  6. Characteristics of randomised trials on diseases in the digestive system registered in ClinicalTrials.gov: a retrospective analysis.

    PubMed

    Wildt, Signe; Krag, Aleksander; Gluud, Liselotte

    2011-01-01

    Objectives To evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published trials. Methods Randomised phase III trials on adult patients with gastrointestinal diseases registered before January 2009 in http://ClinicalTrials.gov were eligible for inclusion. From http://ClinicalTrials.gov all data elements in the database required by the International Committee of Medical Journal Editors (ICMJE) member journals were extracted. The subsequent publications for registered trials were identified. For published trials, data concerning publication date, primary and secondary endpoint, sample size, and whether the journal adhered to ICMJE principles were extracted. Differences between primary and secondary outcomes, sample size and sample size calculations data in http://ClinicalTrials.gov and in the published paper were registered. Results 105 trials were evaluated. 66 trials (63%) were published. 30% of trials were registered incorrectly after their completion date. Several data elements of the required ICMJE data list were not filled in, with missing data in 22% and 11%, respectively, of cases concerning the primary outcome measure and sample size. In 26% of the published papers, data on sample size calculations were missing and discrepancies between sample size reporting in http://ClinicalTrials.gov and published trials existed. Conclusion The quality of registration of randomised controlled trials still needs improvement.

  7. Optimal design of clinical trials with computer simulation based on results of earlier trials, illustrated with a lipodystrophy trial in HIV patients.

    PubMed

    Abbas, Ismail; Rovira, Joan; Casanovas, Josep; Greenfield, Tony

    2008-12-01

    The designer of a clinical trial needs to make many assumptions about real-life practice based on prior knowledge. Simulation allows us to learn from experience by using the information obtained from a trial to improve the original estimators of population parameters. We propose using data from a previous trial to formulate assumptions that can be used to simulate trials and thus improve the design of new trials. To demonstrate our method, we used data from a real clinical trial which had been designed to evaluate cholesterol level changes as a surrogate marker for lipodystrophy in HIV patients. We were able to identify the optimal design that would have minimised the cost of a trial subject to a statistical power constraint which could then be used to design a new trial. In particular, we focused on three factors: the distribution of cholesterol levels in HIV patients, trial recruitment rates and trial dropout rates. We were able to verify our hypothesis that the total cost resulting from carrying out a clinical trial can be minimised by applying simulation models as an alternative to conventional approaches. In our findings the simulation model proved to be very intuitive and a useful method for testing the performance of investigators' assumptions and generating an optimal clinical trial design before being put into practice in the real world. In addition, we concluded that simulation models provide a more accurate determination of power than conventional approaches, thus minimising the total cost of clinical trials.

  8. Centralized National Ethical Review of Clinical Trials in Croatia

    PubMed Central

    Vitezić, Dinko; Lovrek, Maja; Tomić, Siniša

    2009-01-01

    Aim To present the Croatian system of ethical review of clinical trials and assessment outcomes of the applications reviewed by the Croatian Central Ethics Committee. Methods Clinical trial applications reviewed by the Croatian Central Ethics Committee, which has the legal mandate to review clinical trials of medicinal products and medical devices, were retrospectively analyzed from May 2004 to the end of 2008 according to the number, research area, and type of opinion issued. Applications from 2008 were analyzed separately according to the study phase, participants (adult trials vs pediatric trials), and sponsor (commercial trials vs academic trials). Data were analyzed by descriptive statistics. Results Since its establishment in 2004, the Croatian Central Ethics Committee has reviewed 407 trials. The greatest number of clinical trials was in the field of oncology (n = 69), mental and behavioral disorders (n = 52), and endocrine, nutritional, and metabolic diseases (n = 50). In the initial assessment of clinical trials, 60% applications received a conditionally positive opinion. In 28% of applications, the opinion had to be postponed because additional documentation or explanations were required. In 2008, the Croatian Central Ethics Committee reviewed 99 trials, most of which were phase III trials (n = 57). Five clinical trials included pediatric population and 3 were academic clinical trials. Conclusion The model of centralized clinical trial review seems to be appropriate for the current number of clinical trials conducted in Croatia. The efficient and standardized review process of clinical trials by the Central Ethics Committee may positively affect the increasing number of clinical trials conducted in Croatia. Future development includes the transparency of the clinical trials through a publically available database and establishing the basis for conducting academic clinical trials. PMID:19399943

  9. Neurosurgical Randomized Controlled Trials-Distance Travelled.

    PubMed

    Azad, Tej D; Veeravagu, Anand; Mittal, Vaishali; Esparza, Rogelio; Johnson, Eli; Ioannidis, John P A; Grant, Gerald A

    2017-06-21

    The evidence base for many neurosurgical procedures has been limited. We performed a comprehensive and systematic analysis of study design, quality of reporting, and trial results of neurosurgical randomized controlled trials (RCTs). To systematically assess the design and quality characteristics of neurosurgical RCTs. From January 1961 to June 2016, RCTs with >5 patients assessing any 1 neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. The median sample size in the 401 eligible RCTs was 73 patients with a mean patient age of 49.6. Only 111 trials (27.1%) described allocation concealment, 140 (34.6%) provided power calculations, and 117 (28.9%) were adequately powered. Significant efficacy or trend for efficacy was claimed in 226 reports (56.4%), no difference between the procedures was found in 166 trials (41.4%), and significant harm was reported in 9 trials (2.2%). Trials with a larger sample size were more likely to report randomization mode, specify allocation concealment, and power calculations (all P < .001). Government funding was associated with better specification of power calculations ( P = .008) and of allocation concealment ( P = .026), while industry funding was associated with reporting significant efficacy ( P = .02). Reporting of funding, specification of randomization mode and primary outcomes, and mention of power calculations improved significantly (all, P < .05) over time. Several aspects of the design and reporting of RCTs on neurosurgical procedures have improved over time. Better powered and accurately reported trials are needed in neurosurgery to deliver evidence-based care and achieve optimal outcomes.

  10. The Steroids for Corneal Ulcers Trial

    PubMed Central

    Srinivasan, Muthiah; Mascarenhas, Jeena; Rajaraman, Revathi; Ravindran, Meenakshi; Lalitha, Prajna; Glidden, David V.; Ray, Kathryn J.; Hong, Kevin C.; Oldenburg, Catherine E.; Lee, Salena M.; Zegans, Michael E.; McLeod, Stephen D.; Lietman, Thomas M.; Acharya, Nisha R.

    2013-01-01

    Objectives To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity. Methods Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbio-logical results, and patient demographics, for patients enrolled in the trial. Results Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P=.04) and deeper infiltrates (P=.04) and were more likely to be localized centrally (P=.002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n=366, 72%). Conclusions The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation. PMID:21987581

  11. Effect of Industry Sponsorship on Dental Restorative Trials.

    PubMed

    Schwendicke, F; Tu, Y-K; Blunck, U; Paris, S; Göstemeyer, G

    2016-01-01

    Industry sponsorship was found to potentially introduce bias into clinical trials. We assessed the effects of industry sponsorship on the design, comparator choice, and findings of randomized controlled trials on dental restorative materials. A systematic review was performed via MEDLINE, CENTRAL, and EMBASE. Randomized trials on dental restorative and adhesive materials published 2005 to 2015 were included. The design of sponsored and nonsponsored trials was compared statistically (risk of bias, treatment indication, setting, transferability, sample size). Comparator choice and network geometry of sponsored and nonsponsored trials were assessed via network analysis. Material performance rankings in different trial types were estimated via Bayesian network meta-analysis. Overall, 114 studies were included (15,321 restorations in 5,232 patients). We found 21 and 41 (18% and 36%) trials being clearly or possibly industry sponsored, respectively. Trial design of sponsored and nonsponsored trials did not significantly differ for most assessed items. Sponsored trials evaluated restorations of load-bearing cavities significantly more often than nonsponsored trials, had longer follow-up periods, and showed significantly increased risk of detection bias. Regardless of sponsorship status, comparisons were mainly performed within material classes. The proportion of trials comparing against gold standard restorative or adhesive materials did not differ between trial types. If ranked for performance according to the need to re-treat (best: least re-treatments), most material combinations were ranked similarly in sponsored and nonsponsored trials. The effect of industry sponsorship on dental restorative trials seems limited.

  12. Lung-MAP Launches: First Precision Medicine Trial From National Clinical Trials Network

    Cancer.gov

    A unique public-private collaboration today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial, a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinom

  13. Using regional broccoli trial data to select experimental hybrids for input into advanced yield trials

    USDA-ARS?s Scientific Manuscript database

    A large amount of phenotypic trait data are being generated in regional trials that are implemented as part of the Specialty Crop Research Initiative (SCRI) project entitled “Establishing an Eastern Broccoli Industry”. These data are used to identify the best entries in the trials for inclusion in ...

  14. Explanatory and pragmatic clinical trials: a primer and application to a recent asthma trial.

    PubMed

    Sackett, David L

    2011-01-01

    Most clinical trials assessing the role of a specific intervention attempt to answer an explanatory question: under ideal circumstances of risk and responsiveness, can the expert care of individual with a particular condition reduce their risks of a relevant but restricted set of outcomes? Such explanatory trials (also called efficacy trials) are of direct relevance to expert clinicians and their highly compliant patients. Another question, potentially of broader clinical or health care policy relevance is: Does this treatment improve patient-important outcomes when applied by typical clinicians to typical patients? Answering this latter question is the goal of pragmatic trial, also labeled by some as "management" or "effectiveness" trial. The methodological and organizational differences between explanatory and pragmatic trials include, among others, patients eligibility (restricted to highly responsive and compliant patients in explanatory trials vs. everyone with condition of interest in pragmatic trials), experimental and comparator intervention (blinded and inflexible with strict instructions vs. flexible with cross-over permitted and no blinding), types of practitioners (only those with documented high expertise vs. all who usually provide given mode of care), and outcome measurement (often limited to biologic effects vs. broad overall health effects sometimes based on administrative data bases on mortality and utilization). Those aspects of study design and conduct and their role in determining a place of an intervention in clinical practice are reviewed in this paper.

  15. Rape Trial Coverage on Trial: The Myth, the Reality, the Result.

    ERIC Educational Resources Information Center

    Drucker, Susan J.; Hunold, Janice Platt

    Coverage of the New Bedford Massachusetts "Big Dan's Tavern Rape Trial" by Cable News Network (CNN) television cameras was ostensibly for educational purposes, to examine how rape victims are treated in court and how the judicial process works in general. However, the sensational nature of the trial strongly suggests that it was…

  16. The Trial of Napoleon: A Case Study for Using Mock Trials.

    ERIC Educational Resources Information Center

    MacKay, Charles

    2000-01-01

    Describes a course entitled "The Trial of Napoleon Bonaparte" that focuses on a fictitious mock trial of Napoleon Bonaparte to answer the question: did Napoleon pervert or preserve the gain of the French Revolution? Discusses the strengths and weaknesses of the course. (CMK)

  17. The Trial of Napoleon: A Case Study for Using Mock Trials.

    ERIC Educational Resources Information Center

    MacKay, Charles

    2000-01-01

    Describes a course entitled "The Trial of Napoleon Bonaparte" that focuses on a fictitious mock trial of Napoleon Bonaparte to answer the question: did Napoleon pervert or preserve the gain of the French Revolution? Discusses the strengths and weaknesses of the course. (CMK)

  18. Mind the gap: An empirical study of post-trial access in HIV biomedical prevention trials.

    PubMed

    Haire, Bridget; Jordens, Christopher

    2015-08-01

    The principle of providing post-trial access for research participants to successful products of that research is widely accepted and has been enshrined in various declarations and guidelines. While recent ethical guidelines recognise that the responsibility to provide post-trial access extends to sponsors, regulators and government bodies as well as to researchers, it is the researchers who have the direct duty of care to participants. Researchers may thus need to act as advocates for trial participants, especially where government bodies, sponsors, and regulatory bodies have complex interests vested in decisions about whether or not new interventions are made available, how, and to whom. This paper provides an empirical account of post-trial access in the context of HIV prevention research. It describes both access to the successful products of research and the provision antiretroviral drugs for trial participants who acquire HIV. First, we provide evidence that, in the current system, there is considerable variation in the duration and timeliness of access. We then argue that by analysing the difficulties faced by researchers to this point, and their efforts to meet this obligation, much can be learned about how to secure post-trial access in HIV biomedical preventions trials. While researchers alone have a limited obligation, their advocacy on behalf of trial participants may be necessary to call the other parties to account. © 2013 John Wiley & Sons Ltd.

  19. Massed Trials versus Trials Embedded into Game Play: Child Outcomes and Preference

    ERIC Educational Resources Information Center

    Ledford, Jennifer R.; Chazin, Kate T.; Harbin, Emilee R.; Ward, Sarah E.

    2017-01-01

    Limited data are available regarding how response prompting procedures should be used in early childhood settings. The purpose of this study was to compare the efficiency of progressive time delay instruction presented via two trial arrangements: massed and embedded. During massed trial sessions, a short instructional session was conducted,…

  20. Evaluation Studies of the Nuffield A-level Biology Trials - 5. Students after the Trials

    ERIC Educational Resources Information Center

    Kelly, P. J.

    1972-01-01

    The final part of a five-part series reporting the results of the evaluation of the trial version of the Nuffield A-level Biology Project presents data from a follow-up study of students one year after they completed the trials. Student perception of the objectives of the course is reported, and employer or supervisor comments on strengths and…

  1. UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

    PubMed

    Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

    2012-04-28

    Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and

  2. OARSI Clinical Trials Recommendations: Design and conduct of implementation trials of interventions for osteoarthritis.

    PubMed

    Allen, K D; Bierma-Zeinstra, S M A; Foster, N E; Golightly, Y M; Hawker, G

    2015-05-01

    Rigorous implementation research is important for testing strategies to improve the delivery of effective osteoarthritis (OA) interventions. The objective of this manuscript is to describe principles of implementation research, including conceptual frameworks, study designs and methodology, with specific recommendations for randomized clinical trials of OA treatment and management. This manuscript includes a comprehensive review of prior research and recommendations for implementation trials. The review of literature included identification of seminal articles on implementation research methods, as well as examples of previous exemplar studies using these methods. In addition to a comprehensive summary of this literature, this manuscript provides key recommendations for OA implementation trials. This review concluded that to date there have been relatively few implementation trials of OA interventions, but this is an emerging area of research. Future OA clinical trials should routinely consider incorporation of implementation aims to enhance translation of findings.

  3. [Performing clinical trials efficiently in Japan--independent clinical trials and GCP].

    PubMed

    Kanai, Masatoshi; Suzuki-Nishimura, Tamiko

    2007-06-01

    Part of the revision of the Pharmaceutical Affairs Law in 2002 included the establishment of a system for independent clinical trials. According to the partial revision of the Guideline for Good Clinical Practice (GCP), MHLW Ministerial Ordinance No. 106 dated June 12, 2003, independent clinical trials are now recognized in Japan. MHLW promotes to resolve the issues about compliance with good clinical practice (GCP) guideline and the management of the clinical trials, including independent clinical trials. For our nation, more effective and safer new drug applications based on domestic independent clinical trial documents will soon be reviewed by the Pharmaceuticals and Medical Devices Agency (PMDA). For the protection of human rights, important issues about quality control and quality assurance raised by GCP Audit consist of both GCP on-site review and Document-based Conformity Review by the Office of Conformity Audit of the PMDA are studied.

  4. Challenging Issues in Clinical Trial Design: Part 4 of a 4-Part Series on Statistics for Clinical Trials.

    PubMed

    Pocock, Stuart J; Clayton, Tim C; Stone, Gregg W

    2015-12-29

    As a sequel to last week's paper on the fundamentals of clinical trial design, this paper tackles related controversial issues: noninferiority trials, the value of factorial designs, the importance and challenges of strategy trials, Data Monitoring Committees (including when to stop a trial early), and the role of adaptive designs. All topics are illustrated by relevant examples from cardiology trials. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Publication and non-publication of drug trial results: a 10-year cohort of trials in Norwegian general practice.

    PubMed

    Brænd, Anja Maria; Straand, Jørund; Jakobsen, Rune Bruhn; Klovning, Atle

    2016-04-11

    Previously, we identified a 10-year cohort of protocols from applications to the Norwegian Medicines Agency 1998-2007, consisting of 196 drug trials in general practice. The aim of this study was to examine whether trial results were published and whether trial funding and conflicts of interest were reported. Cohort study of trials with systematic searches for published results. Clinical drug trials in Norwegian general practice. We performed systematic literature searches of MEDLINE, Embase and CENTRAL to identify publications originating from each trial using characteristics such as test drug, comparator and patient groups as search terms. When no publication was identified, we contacted trial sponsors for information regarding trial completion and reference to any publications. We determined the frequency of publication of trial results and trial characteristics associated with publication of results. Of the 196 trials, 5 were never started. Of the remaining 191 trials, 71% had results published in a journal, 11% had results publicly available elsewhere and 18% of trials had no results available. Publication was more common among trials with an active comparator drug (χ(2) test, p=0.040), with a larger number of patients (total sample size≥median, p=0.010) and with a longer trial period (duration≥median, p=0.025). Trial funding was reported in 85% of publications and increased over time, as did reporting of conflicts of interest among authors. Among the 134 main journal articles from the trials, 60% presented statistically significant results for the investigational drug, and the conclusion of the article was favourable towards the test drug in 78% of papers. We did not identify any journal publication of results for 29% of the general practice drug trials. Trials with an active comparator, larger and longer trials were more likely to be published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  6. Publication and non-publication of drug trial results: a 10-year cohort of trials in Norwegian general practice

    PubMed Central

    Brænd, Anja Maria; Straand, Jørund; Jakobsen, Rune Bruhn; Klovning, Atle

    2016-01-01

    Objectives Previously, we identified a 10-year cohort of protocols from applications to the Norwegian Medicines Agency 1998–2007, consisting of 196 drug trials in general practice. The aim of this study was to examine whether trial results were published and whether trial funding and conflicts of interest were reported. Design Cohort study of trials with systematic searches for published results. Setting Clinical drug trials in Norwegian general practice. Methods We performed systematic literature searches of MEDLINE, Embase and CENTRAL to identify publications originating from each trial using characteristics such as test drug, comparator and patient groups as search terms. When no publication was identified, we contacted trial sponsors for information regarding trial completion and reference to any publications. Main outcome measures We determined the frequency of publication of trial results and trial characteristics associated with publication of results. Results Of the 196 trials, 5 were never started. Of the remaining 191 trials, 71% had results published in a journal, 11% had results publicly available elsewhere and 18% of trials had no results available. Publication was more common among trials with an active comparator drug (χ2 test, p=0.040), with a larger number of patients (total sample size≥median, p=0.010) and with a longer trial period (duration≥median, p=0.025). Trial funding was reported in 85% of publications and increased over time, as did reporting of conflicts of interest among authors. Among the 134 main journal articles from the trials, 60% presented statistically significant results for the investigational drug, and the conclusion of the article was favourable towards the test drug in 78% of papers. Conclusions We did not identify any journal publication of results for 29% of the general practice drug trials. Trials with an active comparator, larger and longer trials were more likely to be published. PMID:27067893

  7. Clinical trials profile: professionals and sites.

    PubMed

    Paschoale, Helena S; Barbosa, Fernanda R; Nita, Marcelo E; Carrilho, Flair J; Ono-Nita, Suzane Kioko

    2010-09-01

    Clinical trial is considered a breakthrough method in medicine and essential to the development of new drugs. Clinical trials that comply with international and national regulations require an appropriate infrastructure and team qualification. The goal of this study was to evaluate clinical trial groups in Brazil: professional qualification, site structure regulatory knowledge and Good Clinical Practice (GCP) adherence. This is a transversal study with investigators (PI) and sub investigator (SI). PI and SI data were initially identified from Curriculum Lattes from National Advice of Scientific and Technological Development. The study participants were submitted to a questionnaire, which was composed of qualitative and quantitative questions. A hundred PI and SI were interviewed. The most representative Brazilian regions were Southeast (68%) and South (18%). The main institutions involved were HCFMUSP complex and UNIFESP among others institutions. Academic graduation is observed in 86% of them and the higher degree is Doctorate (62%). 91% had GCP knowledge although only 74% had formal training. About the team, all of them are multidisciplinary with majority of nurses and pharmaceuticals. 88% had GCP knowledge although only 77% had formal training. 36%, 60% and 44% of clinical trials were in phase II, III and IV. In conclusion, researchers have appropriate skills and knowledge to perform clinical studies however there is still a need for training. The centers where the researchers work, have trained staff and adequate infrastructure for conducting clinical trials phase II, III and IV.

  8. [Role of government in clinical trials].

    PubMed

    Mazzetti, Pilar; Silva-Paredes, Gustavo; Cornejo-Olivas, Mario

    2012-01-01

    The regulation of clinical trials by the Government is a process of continuous change and adaptation, current challenge is to ensure the safety of participants and get balance of administrative procedures. Development and regulation of clinical trials in different countries vary according to the situation, context national or international execution, determining the insufficiency of national regulation requiring review of international regulation. The aim of this publication is to present a comprehensive overview of the role of Government in the regulation of clinical trials in different realities. It includes a review of the regulation in The European Union, The United States and some Latin American countries and finally the regulation in Peru. Contemporary trends in the regulation of clinical trials, are characterized by increasing standards of quality, ensuring the safety of the participants, promote transparency, lower bureaucratic processes and strengthening ethics IRB committees in the framework of open democratic processes, involving all stakeholders in dynamic processes based on current knowledge and changing tendencies. The challenge is to promote the development of clinical trials from the government institutions (universities, research centers, institutes, hospitals, etc.) priorizing local needs including orphan drugs, prevalent and neglected diseases, and therapeutic use of active components of local native plants.

  9. Ethical issues in naturalistic versus controlled trials

    PubMed Central

    Helmchen, Hanfried

    2011-01-01

    Ethical core issues in research with human subjects are related to informed consent and risk-benefit assessment. This is valid for all types of studies. However, there has been much greater focus of ethical considerations on controlled clinical trials than on naturalistic trials, probably because the former are interventional in nature and may have unknown and perhaps severe somatic risks, whereas naturalistic studies seem not to intervene but only to observe, and therefore are assumed to have fewer or almost no risks. However, there are also ethical implications in naturalistic trials, although their weight is differently accentuated, more with potential, more with potential psychological burdens of the observational procedures and more with potential physical risks in interventional trials. This will be elaborated with examples of placebo-controlled trials and of incidental findings in screenings, of marketing influences on observational studies, and of psychological burdens by survey interviews. The ethical implications wilt be analyzed within a more general framework, Finally, recommendations will be offered. PMID:21842614

  10. Sufficient trial size to inform clinical practice

    PubMed Central

    Manski, Charles F.; Tetenov, Aleksey

    2016-01-01

    Medical research has evolved conventions for choosing sample size in randomized clinical trials that rest on the theory of hypothesis testing. Bayesian statisticians have argued that trials should be designed to maximize subjective expected utility in settings of clinical interest. This perspective is compelling given a credible prior distribution on treatment response, but there is rarely consensus on what the subjective prior beliefs should be. We use Wald’s frequentist statistical decision theory to study design of trials under ambiguity. We show that ε-optimal rules exist when trials have large enough sample size. An ε-optimal rule has expected welfare within ε of the welfare of the best treatment in every state of nature. Equivalently, it has maximum regret no larger than ε. We consider trials that draw predetermined numbers of subjects at random within groups stratified by covariates and treatments. We report exact results for the special case of two treatments and binary outcomes. We give simple sufficient conditions on sample sizes that ensure existence of ε-optimal treatment rules when there are multiple treatments and outcomes are bounded. These conditions are obtained by application of Hoeffding large deviations inequalities to evaluate the performance of empirical success rules. PMID:27601679

  11. Optimizing Trial Designs for Targeted Therapies

    PubMed Central

    Beckman, Robert A.; Burman, Carl-Fredrik; König, Franz; Stallard, Nigel; Posch, Martin

    2016-01-01

    An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment is tested in an overall population and/or in a pre-specified subpopulation. Based on a decision theoretic framework we derive optimized trial designs by maximizing utility functions. Features to be optimized include the sample size and the population in which the trial is performed (the full population or the targeted subgroup only) as well as the underlying multiple test procedure. The approach accounts for prior knowledge of the efficacy of the drug in the considered populations using a two dimensional prior distribution. The considered utility functions account for the costs of the clinical trial as well as the expected benefit when demonstrating efficacy in the different subpopulations. We model utility functions from a sponsor’s as well as from a public health perspective, reflecting actual civil interests. Examples of optimized trial designs obtained by numerical optimization are presented for both perspectives. PMID:27684573

  12. Quantitative Imaging in Cancer Clinical Trials

    PubMed Central

    Yankeelov, Thomas E.; Mankoff, David A.; Schwartz, Lawrence H.; Lieberman, Frank S.; Buatti, John M.; Mountz, James M.; Erickson, Bradley J.; Fennessy, Fiona M.M.; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L.; Linden, Hannah M.; Kinahan, Paul; Zhao, Binsheng; Hylton, Nola M.; Gillies, Robert J.; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L.

    2015-01-01

    As anti-cancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. While traditional, anatomic CT and MRI exams are useful in many settings, there is increasing evidence that these methods cannot answer the fundamental biological and physiological questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients, and to provide a more efficient path for the development of improved targeted therapies. PMID:26773162

  13. Public information about clinical trials and research.

    PubMed

    Plétan, Yannick; Zannad, Faïez; Jaillon, Patrice

    2003-01-01

    Be it to restore the confused image of clinical research in relation to the lay public, or to develop new ways of accruing healthy volunteers or patients for clinical trials, there is a need to draft some guidance on how best to provide information on research. Although the French legal and regulatory armamentarium in this area is essentially liberal, there is currently little-justified reluctance among study sponsors to advertise publicly. A group of academic and pharmaceutical industry researchers, assembled for a workshop, together with regulators, journalists, representatives from ethics committees, social security, patient and health consumer groups and other French institutional bodies, has suggested the following series of recommendations: there is no need for additional legal or regulatory constraints; sponsors should be aware of and make use of direct public information on trials; a 'good practice charter' on public communication about clinical trials should be developed; all professionals should be involved in this communication platform; communication in the patient's immediate vicinity should be preferred (primary-care physician, local press); clinical databases and websites accessible to professionals, but also to patients and non-professionals, should be developed; genuine instruction on clinical trials for physicians and health professionals unfamiliar with such trials should be developed and disseminated; media groups should receive at least some training in the fundamentals of clinical research.

  14. Quantitative Imaging in Cancer Clinical Trials.

    PubMed

    Yankeelov, Thomas E; Mankoff, David A; Schwartz, Lawrence H; Lieberman, Frank S; Buatti, John M; Mountz, James M; Erickson, Bradley J; Fennessy, Fiona M M; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L; Linden, Hannah M; Kinahan, Paul E; Zhao, Binsheng; Hylton, Nola M; Gillies, Robert J; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L

    2016-01-15

    As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.

  15. Quality of clinical trials: A moving target

    PubMed Central

    Bhatt, Arun

    2011-01-01

    Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

  16. Prostate cancer vaccines in clinical trials.

    PubMed

    Lubaroff, David M

    2012-07-01

    This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.

  17. Trial Registration at ClinicalTrials.gov between May and October 2005

    PubMed Central

    Zarin, Deborah A.; Tse, Tony; Ide, Nicholas C.

    2006-01-01

    BACKGROUND Clinical trial registration allows interested parties to obtain information about ongoing and completed trials, but there are few data indicating the quality of the information provided during the registration process. We used information in the publicly available ClinicalTrials.gov database to describe patterns of trial registration before and after the implementation by journal editors of a new policy requiring registration as a prerequisite for publication. METHODS We reviewed ClinicalTrials.gov records to determine patterns of completion of the “Intervention Name” and “Primary Outcome Measure” data fields for trials registered on May 20 and October 11, 2005, and for trials registered during the interval between these two dates, inclusively. RESULTS During the interval studied, the number of registrations in ClinicalTrials.gov increased by 73 percent from 13,153 to 22,714. The percentage of interventional trials registered by industry with nonspecific Intervention Name entries (attributable to four drug companies) decreased from 10 percent to 2 percent; all other industry and nonindustry records contained specific entries in this field. Of the 2670 studies registered by industry between the two dates, 76 percent provided information in the Primary Outcome Measure field, although these entries varied markedly in their degree of specificity. In the remaining 24 percent of the records, this field was blank. CONCLUSIONS During the summer of 2005, there were large increases in the number of clinical trial registrations. Overall, the data contained in records were more complete in October than they were in May, but there still is room for substantial improvement. PMID:16382064

  18. Advances in cardiology: clinical trial update.

    PubMed

    Howe, Andrew J; Shand, James A; Menown, Ian B A

    2011-05-01

    Multiple key cardiology trials have been presented or published over recent months, several with the potential to change clinical practice. In this article, we summarize and place in clinical context new trial findings regarding anticoagulation in the cardiac catheterization laboratory (enoxaparin, fondaparinux and unfractionated heparin), the implications of genetic polymorphisms and functional testing for antiplatelet therapy (clopidogrel and ticagrelor), new oral anticoagulants for use in atrial fibrillation (apixiban and rivaroxaban), optimal pacing strategies and pharmacological agents in heart failure (ivabradine, eplerenone, cardiac resynchronization therapy, telemonitoring and intracoronary bone marrow stem cell infusion). Clinical trials in percutaneous structural intervention (transcatheter aortic valve implantation, MONARC™ mitral annular implant, STARFlex(®) patent foramen ovale device) and advanced percutaneous coronary intervention (everolimus-eluting stents, biodegradable polymer/polymer-free technologies and contemporary use of intravascular ultrasound) are also discussed.

  19. Clinical trials for stem cell therapies

    PubMed Central

    2011-01-01

    In recent years, clinical trials with stem cells have taken the emerging field in many new directions. While numerous teams continue to refine and expand the role of bone marrow and cord blood stem cells for their vanguard uses in blood and immune disorders, many others are looking to expand the uses of the various types of stem cells found in bone marrow and cord blood, in particular mesenchymal stem cells, to uses beyond those that could be corrected by replacing cells in their own lineage. Early results from these trials have produced mixed results often showing minor or transitory improvements that may be attributed to extracellular factors. More research teams are accelerating the use of other types of adult stem cells, in particular neural stem cells for diseases where beneficial outcome could result from either in-lineage cell replacement or extracellular factors. At the same time, the first three trials using cells derived from pluripotent cells have begun. PMID:21569277

  20. Franz Kafka's The Trial: guilty or innocent?

    PubMed

    Siegel, E

    1996-07-01

    Through an examination of The Trial by Kafka I attempt to show that the depiction of the Court apparatus is dynamically related to the commission of unconscious crimes of the type we encounter in our patients. To provide a context for the novel, I discuss Kafka's biography and some possible unconscious motivations. My goal is to show how the concept of a particular type of superego pressure can be used to understand the subtle irony in The Trial. Although Joseph K.'s behavior frequently involves oedipal crimes, there are many preoedipal themes that help account for his experience of the Court. I contrast this psychoanalytic understanding of K.'s guilt with that of literary critics who interpret The Trial as an allegory of guilt but who minimize the psychological dimensions.

  1. Missing data handling in chronic pain trials.

    PubMed

    Kim, Yongman

    2011-03-01

    In chronic pain trials, proper handling of missing data due to dropout is an important issue because the dropout rate is high and the study conclusion may depend on the method chosen. The intent-to-treat (ITT) principle usually requires imputations for missing data to include the dropouts as well as completers in the statistical analysis. However, a statistical analysis with imputation might lead to a misinterpretation of clinical data. In chronic pain trials, treatment-related dropouts are clinical outcomes themselves. For example, an early dropout due to toxicity usually indicates a treatment failure, as does a dropout due to lack of efficacy. Problems with traditional methods such as last observation carried forward (LOCF) or baseline observation carried forward (BOCF) are identified especially in the chronic pain setting. Alternative methods, such as continuous responder analysis and two-part model analysis, treating dropouts as clinical events, are introduced with an example of osteoarthritis clinical trial data.

  2. Cooperative Group Trials in the Community Setting

    PubMed Central

    Wade, James Lloyd; Petrelli, Nicholas J.; McCaskill-Stevens, Worta

    2015-01-01

    Over the last 40 years the National Cancer Institute (NCI) has created a vibrant public-private partnership for the implementation of NCI sponsored cooperative group (Network) clinical trials throughout the United States and Canada. Over these four decades, the cancer clinical trials process has become more complex more precise and more resource intensive. During this same time period, financial resources to support the NCI community research initiative have become more constrained. The newest manifestation of NCI sponsored community based cancer clinical trial research, known as the National Community Oncology Research Program (NCORP) began initial operation August 1st, 2014. This paper describes several key strategies that community sites may use to not only be successful, but to thrive in this new financially austere research environment. PMID:26433550

  3. [Radiotherapy phase I trials' methodology: Features].

    PubMed

    Rivoirard, R; Vallard, A; Langrand-Escure, J; Guy, J-B; Ben Mrad, M; Yaoxiong, X; Diao, P; Méry, B; Pigne, G; Rancoule, C; Magné, N

    2016-12-01

    In clinical research, biostatistical methods allow the rigorous analysis of data collection and should be defined from the trial design to obtain the appropriate experimental approach. Thus, if the main purpose of phase I is to determine the dose to use during phase II, methodology should be finely adjusted to experimental treatment(s). Today, the methodology for chemotherapy and targeted therapy is well known. For radiotherapy and chemoradiotherapy phase I trials, the primary endpoint must reflect both effectiveness and potential treatment toxicities. Methodology should probably be complex to limit failures in the following phases. However, there are very few data about methodology design in the literature. The present study focuses on these particular trials and their characteristics. It should help to raise existing methodological patterns shortcomings in order to propose new and better-suited designs.

  4. Cooperative Group Trials in the Community Setting.

    PubMed

    Lloyd Wade, James; Petrelli, Nicholas J; McCaskill-Stevens, Worta

    2015-10-01

    Over the last 40 years the National Cancer Institute (NCI) has created a vibrant public-private partnership for the implementation of NCI-sponsored cooperative group (Network) clinical trials throughout the United States and Canada. Over these four decades, the cancer clinical trials process has become more complex more precise and more resource intensive. During this same time period, financial resources to support the NCI community research initiative have become more constrained. The newest manifestation of NCI-sponsored community based cancer clinical trial research, known as the National Community Oncology Research Program (NCORP) began initial operation August 1, 2014. We describe several key strategies that community sites may use to not only be successful but to thrive in this new financially austere research environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. [Clinical trials: principles of the method].

    PubMed

    Aboulker, J P

    2000-04-15

    Comparative judgement, which is seminal to any kind of science performing measurements, has been applied to clinical reasoning for many centuries. The need for systematizing the observational methods used in medicine in order to draw more reliable inferences about the effects of therapies has been active all along the 19th century. This has resulted in controlled studies which yielded important advances in clinical and therapeutic knowledge, although their designs were not fully satisfactory. Clinical trials have gained their status of "hard science", methodology allowing causal inference, by the end of the 1940s after having adopted the statistical theories developed in the 1930s by Fisher for experimental design in agronomy. A long way has been run since the first controlled randomized trial. However, half a century later, modern clinical trial remains essentially a controlled randomized prospective study using methods to limit potential biases and to establish statistical significance.

  6. Are outcome-adaptive allocation trials ethical?

    PubMed

    Hey, Spencer Phillips; Kimmelman, Jonathan

    2015-04-01

    Randomization is firmly established as a cornerstone of clinical trial methodology. Yet, the ethics of randomization continues to generate controversy. The default, and most efficient, allocation scheme randomizes patients equally (1:1) across all arms of study. However, many randomized trials are using outcome-adaptive allocation schemes, which dynamically adjust the allocation ratio in favor of the better performing treatment arm. Advocates of outcome-adaptive allocation contend that it better accommodates clinical equipoise and promotes informed consent, since such trials limit patient-subject exposure to sub-optimal care. In this essay, we argue that this purported ethical advantage of outcome-adaptive allocation does not stand up to careful scrutiny in the setting of two-armed studies and/or early-phase research.

  7. Tooth whitening clinical trials: a global perspective.

    PubMed

    Gerlach, Robert W

    2007-09-01

    Tooth whitening has been the subject of extensive clinical trials research since the introduction of the first hydrogen-peroxide whitening strips in 2000. Availability of digital image analysis, an unambiguous and reproducible method for assessing color change, has contributed to global clinical research and product development on whitening strips. The research has included a series of global randomized controlled trials in distinct sites and cultures, involving 6-6.5% hydrogen peroxide whitening strips used for 7-21 days. These studies, conducted at research hospitals, dental schools, and private dental practice, demonstrated significant color improvement with whitening strips relative to baseline and/or various controls without serious adverse events. This integrated clinical trials research provides important evidence of long-term safety and effectiveness of tooth whitening with 6-6.5% hydrogen peroxide whitening strips.

  8. Trials, tricks and transparency: how disclosure rules affect clinical knowledge.

    PubMed

    Dahm, Matthias; González, Paula; Porteiro, Nicolás

    2009-12-01

    Scandals of selective reporting of clinical trial results by pharmaceutical firms have underlined the need for more transparency in clinical trials. We provide a theoretical framework which reproduces incentives for selective reporting and yields three key implications concerning regulation. First, a compulsory clinical trial registry complemented through a voluntary clinical trial results database can implement full transparency (the existence of all trials as well as their results is known). Second, full transparency comes at a price. It has a deterrence effect on the incentives to conduct clinical trials, as it reduces the firms' gains from trials. Third, in principle, a voluntary clinical trial results database without a compulsory registry is a superior regulatory tool; but we provide some qualified support for additional compulsory registries when medical decision-makers cannot anticipate correctly the drug companies' decisions whether to conduct trials.

  9. SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

    PubMed

    Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

    2015-12-01

    The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

  10. Should Sponsors and DSMBs Share Interim Results Across Trials?

    PubMed Central

    Shah, Seema K.; Dawson, Liza; Dixon, Dennis O.; Lie, Reidar K.

    2011-01-01

    Increasing numbers of multinational clinical trials have generated new ethical obligations of research sponsors and their DSMBs. Although sponsors and DSMBs clearly have ethical obligations to protect subjects in their trials, future patients, and the integrity of their trial, the obligations they have to protect subjects in other trials have been overlooked. When interim results from clinical trials can significantly affect the conduct of other trials and the welfare of the subjects in those trials, sponsors and DSMBs may have obligations to disclose results to the relevant parties. We propose that sponsors and DSMBs routinely work together in advance to develop a plan for disclosing relevant information in cases where it is necessary to protect the welfare of subjects in other trials. Channels of communication between sponsors, DSMBs, IRBs, and others involved in similar and concurrent trials will better protect both research participants and the integrity of the research enterprise. PMID:21937922

  11. SPIRIT 2013 statement: defining standard protocol items for clinical trials.

    PubMed

    Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Doré, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

    2013-02-05

    The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

  12. Investigator experiences with financial conflicts of interest in clinical trials.

    PubMed

    Rochon, Paula A; Sekeres, Melanie; Hoey, John; Lexchin, Joel; Ferris, Lorraine E; Moher, David; Wu, Wei; Kalkar, Sunila R; Van Laethem, Marleen; Gruneir, Andrea; Gold, Jennifer; Maskalyk, James; Streiner, David L; Taback, Nathan; Chan, An-Wen

    2011-01-12

    Financial conflicts of interest (fCOI) can introduce actions that bias clinical trial results and reduce their objectivity. We obtained information from investigators about adherence to practices that minimize the introduction of such bias in their clinical trials experience. Email survey of clinical trial investigators from Canadian sites to learn about adherence to practices that help maintain research independence across all stages of trial preparation, conduct, and dissemination. The main outcome was the proportion of investigators that reported full adherence to preferred trial practices for all of their trials conducted from 2001-2006, stratified by funding source. 844 investigators responded (76%) and 732 (66%) provided useful information. Full adherence to preferred clinical trial practices was highest for institutional review of signed contracts and budgets (82% and 75% of investigators respectively). Lower rates of full adherence were reported for the other two practices in the trial preparation stage (avoidance of confidentiality clauses, 12%; trial registration after 2005, 39%). Lower rates of full adherence were reported for 7 practices in the trial conduct (35% to 43%) and dissemination (53% to 64%) stages, particularly in industry funded trials. 269 investigators personally experienced (n = 85) or witnessed (n = 236) a fCOI; over 70% of these situations related to industry trials. Full adherence to practices designed to promote the objectivity of research varied across trial stages and was low overall, particularly for industry funded trials.

  13. Investigator experiences with financial conflicts of interest in clinical trials

    PubMed Central

    2011-01-01

    Background Financial conflicts of interest (fCOI) can introduce actions that bias clinical trial results and reduce their objectivity. We obtained information from investigators about adherence to practices that minimize the introduction of such bias in their clinical trials experience. Methods Email survey of clinical trial investigators from Canadian sites to learn about adherence to practices that help maintain research independence across all stages of trial preparation, conduct, and dissemination. The main outcome was the proportion of investigators that reported full adherence to preferred trial practices for all of their trials conducted from 2001-2006, stratified by funding source. Results 844 investigators responded (76%) and 732 (66%) provided useful information. Full adherence to preferred clinical trial practices was highest for institutional review of signed contracts and budgets (82% and 75% of investigators respectively). Lower rates of full adherence were reported for the other two practices in the trial preparation stage (avoidance of confidentiality clauses, 12%; trial registration after 2005, 39%). Lower rates of full adherence were reported for 7 practices in the trial conduct (35% to 43%) and dissemination (53% to 64%) stages, particularly in industry funded trials. 269 investigators personally experienced (n = 85) or witnessed (n = 236) a fCOI; over 70% of these situations related to industry trials. Conclusion Full adherence to practices designed to promote the objectivity of research varied across trial stages and was low overall, particularly for industry funded trials. PMID:21226951

  14. The Hawthorne Effect: a randomised, controlled trial

    PubMed Central

    McCarney, Rob; Warner, James; Iliffe, Steve; van Haselen, Robbert; Griffin, Mark; Fisher, Peter

    2007-01-01

    Background The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia. Methods Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months). Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). Results We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT), with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group), and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group). There was no significant difference on carer quality of life. Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning. Trial registration Current controlled trials: ISRCTN45577048 PMID:17608932

  15. Lessons from randomised direct comparative trials.

    PubMed

    Achiron, Anat; Fredrikson, Sten

    2009-02-01

    For over a decade, four immunomodulatory therapies have been available for the treatment of relapsing remitting multiple sclerosis. However, few direct comparative data were available to facilitate the choice of treatment. This choice has been influenced by the perception that interferon-beta preparations have greater efficacy than glatiramer acetate, due to apparently more rapid and robust reduction of gadolinium-enhancing lesions seen on magnetic resonance imaging in the pivotal trials of these agents. This situation has changed in the last year, with the outcomes of three randomised clinical trials comparing the efficacy and safety of glatiramer acetate with that of a high-dose interferon-beta in relapsing remitting multiple sclerosis. These are the REGARD, BEYOND and BECOME trials. In the REGARD trial, 764 patients were randomised to treatment with either interferon-beta 1a sc 44 microg or glatiramer acetate for 96 weeks; no significant difference in the time to first relapse was observed. The largest of the three comparative studies, the BEYOND trial, compared treatment with interferon-beta 1b sc 500 microg, interferon-beta 1b sc 250 microg or glatiramer acetate for two years in 2,244 patients. The hazard ratio for multiple relapses was close to unity for comparisons between all groups, indicating equivalent efficacy in all three treatment arms. Relapse rates (around 0.3 relapses/year) in all these studies were much lower than anticipated and lower than those reported a decade previously in the pivotal trials of beta-interferons and glatiramer acetate. No unexpected safety issues were identified in any of these studies. The completion of these direct comparative studies has considerably enriched the clinical evidence database by contributing large numbers of patients. This provides an invaluable contribution for helping the physician make an informed choice about treatment. The results of the direct comparative studies provide evidence that glatiramer acetate

  16. Clustering clinical trials with similar eligibility criteria features.

    PubMed

    Hao, Tianyong; Rusanov, Alexander; Boland, Mary Regina; Weng, Chunhua

    2014-12-01

    To automatically identify and cluster clinical trials with similar eligibility features. Using the public repository ClinicalTrials.gov as the data source, we extracted semantic features from the eligibility criteria text of all clinical trials and constructed a trial-feature matrix. We calculated the pairwise similarities for all clinical trials based on their eligibility features. For all trials, by selecting one trial as the center each time, we identified trials whose similarities to the central trial were greater than or equal to a predefined threshold and constructed center-based clusters. Then we identified unique trial sets with distinctive trial membership compositions from center-based clusters by disregarding their structural information. From the 145,745 clinical trials on ClinicalTrials.gov, we extracted 5,508,491 semantic features. Of these, 459,936 were unique and 160,951 were shared by at least one pair of trials. Crowdsourcing the cluster evaluation using Amazon Mechanical Turk (MTurk), we identified the optimal similarity threshold, 0.9. Using this threshold, we generated 8806 center-based clusters. Evaluation of a sample of the clusters by MTurk resulted in a mean score 4.331±0.796 on a scale of 1-5 (5 indicating "strongly agree that the trials in the cluster are similar"). We contribute an automated approach to clustering clinical trials with similar eligibility features. This approach can be potentially useful for investigating knowledge reuse patterns in clinical trial eligibility criteria designs and for improving clinical trial recruitment. We also contribute an effective crowdsourcing method for evaluating informatics interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Post combustion trials at Dofasco's KOBM furnace

    SciTech Connect

    Farrand, B.L.; Wood, J.E.; Goetz, F.J.

    1992-01-01

    Post combustion trials were conducted at Dofasco's 300 tonne KOBM furnace as part of the AISI Direct Steelmaking Program. The purpose of the project work was to measure the post combustion ratio (PCR) and heat transfer efficiency (HTE) of the post combustion reaction in a full size steelmaking vessel. A method of calculating PCR and HTE using off gas analysis and gas temperature was developed. The PCR and HTE were determined under normal operating conditions. Trials assessed the effect of lance height, vessel volume, foaming slag and pellet additions on PCR and HTE.

  18. Infertility trial outcomes: healthy moms and babies.

    PubMed

    Silver, Robert

    2014-05-01

    Traditionally, the primary outcome of infertility trials has been a positive pregnancy test or a clinically recognized pregnancy. However, parents desire a healthy baby that grows up to be a healthy adult, rather than a positive pregnancy test. Too often results of infertility trials are lacking in crucial obstetric details. This is problematic because treatments for infertility have the capacity to increase the risk for a variety of adverse obstetric outcomes. This review will outline important obstetric variables that should be included when reporting infertility research. The rationale for including these data, precise definitions of the variables, and cost-effective strategies for obtaining these obstetric details will be highlighted.

  19. Ethical Issues in Clinical Trials Involving Nanomedicine

    PubMed Central

    Resnik, David B.; Tinkle, Sally S.

    2009-01-01

    Nanomedicine shows tremendous promise for improving medical diagnosis, treatment, and prevention, but it also raises a variety of ethical concerns. Because of the paucity of data on the physicochemical properties of nanoscale materials in biological systems, clinical trials of nanomedicine products present some unique challenges related to risk minimization, management and communication involving human subjects. Although these clinical trials do not raise any truly novel ethical issues, the rapid development of nanotechnology and its potentially profound social and environmental impacts, add a sense of urgency to the problems that arise. PMID:17166777

  20. Implementing personalized cancer genomics in clinical trials.

    PubMed

    Simon, Richard; Roychowdhury, Sameek

    2013-05-01

    The recent surge in high-throughput sequencing of cancer genomes has supported an expanding molecular classification of cancer. These studies have identified putative predictive biomarkers signifying aberrant oncogene pathway activation and may provide a rationale for matching patients with molecularly targeted therapies in clinical trials. Here, we discuss some of the challenges of adapting these data for rare cancers or molecular subsets of certain cancers, which will require aligning the availability of investigational agents, rapid turnaround of clinical grade sequencing, molecular eligibility and reconsidering clinical trial design and end points.