Clinical trial quality: From supervision to collaboration and beyond.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen

2018-02-01

Over the past decade, clinical trial quality has evolved from an after-the-fact, reactive activity to one focused on the important work of evidence generation from well-designed trials. This article explores the role the Clinical Trials Transformation Initiative has played in advancing quality as a core element of clinical trial design, through project work that initially focused on monitoring but evolved into a holistic, prospective, and comprehensive quality by design approach to clinical trial design and conduct.

Factors associated with reporting results for pulmonary clinical trials in ClinicalTrials.gov.

PubMed

Riley, Isaretta L; Boulware, L Ebony; Sun, Jie-Lena; Chiswell, Karen; Que, Loretta G; Kraft, Monica; Todd, Jamie L; Palmer, Scott M; Anderson, Monique L

2018-02-01

Background/aims The Food and Drug Administration Amendments Act mandates that applicable clinical trials report basic summary results to the ClinicalTrials.gov database within 1 year of trial completion or termination. We aimed to determine the proportion of pulmonary trials reporting basic summary results to ClinicalTrials.gov and assess factors associated with reporting. Methods We identified pulmonary clinical trials subject to the Food and Drug Administration Amendments Act (called highly likely applicable clinical trials) that were completed or terminated between 2008 and 2012 and reported results by September 2013. We estimated the cumulative percentage of applicable clinical trials reporting results by pulmonary disease category. Multivariable Cox regression modeling identified characteristics independently associated with results reporting. Results Of 1450 pulmonary highly likely applicable clinical trials, 380 (26%) examined respiratory neoplasms, 238 (16%) asthma, 175 (12%) chronic obstructive pulmonary disease, and 657 (45%) other respiratory diseases. Most (75%) were pharmaceutical highly likely applicable clinical trials and 71% were industry-funded. Approximately 15% of highly likely applicable clinical trials reported results within 1 year of trial completion, while 55% reported results over the 5-year study period. Earlier phase highly likely applicable clinical trials were less likely to report results compared to phase 4 highly likely applicable clinical trials (phases 1/2 and 2 (adjusted hazard ratio 0.41 (95% confidence interval: 0.31-0.54)), phases 2/3 and 3 (adjusted hazard ratio 0.55 (95% confidence interval: 0.42-0.72)) and phase not applicable (adjusted hazard ratio 0.43 (95% confidence interval: 0.29-0.63)). Pulmonary highly likely applicable clinical trials without Food and Drug Administration oversight were less likely to report results compared with those with oversight (adjusted hazard ratio 0.65 (95% confidence interval: 0

Clinical Trials

MedlinePlus

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

ClinicalTrials.gov

MedlinePlus

... Terms and Conditions Disclaimer ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted ... world. ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ...

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov.

PubMed

Chen, Junchao; Huang, Jihan; Li, Jordan V; Lv, Yinghua; He, Yingchun; Zheng, Qingshan

2017-01-01

The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM.

Standardizing clinical trials workflow representation in UML for international site comparison.

PubMed

de Carvalho, Elias Cesar Araujo; Jayanti, Madhav Kishore; Batilana, Adelia Portero; Kozan, Andreia M O; Rodrigues, Maria J; Shah, Jatin; Loures, Marco R; Patil, Sunita; Payne, Philip; Pietrobon, Ricardo

2010-11-09

With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials

Standardizing Clinical Trials Workflow Representation in UML for International Site Comparison

PubMed Central

de Carvalho, Elias Cesar Araujo; Jayanti, Madhav Kishore; Batilana, Adelia Portero; Kozan, Andreia M. O.; Rodrigues, Maria J.; Shah, Jatin; Loures, Marco R.; Patil, Sunita; Payne, Philip; Pietrobon, Ricardo

2010-01-01

Background With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. Methods Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. Results Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. Conclusions This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative

Active video games to promote physical activity in children with cancer: a randomized clinical trial with follow-up.

PubMed

Kauhanen, Lotta; Järvelä, Liisa; Lähteenmäki, Päivi M; Arola, Mikko; Heinonen, Olli J; Axelin, Anna; Lilius, Johan; Vahlberg, Tero; Salanterä, Sanna

2014-04-05

Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children's cancer treatment. The aim of this study is to evaluate the effect of active video games in promotion of physical activity in children with cancer. The research is conducted as a parallel randomized clinical trial with follow-up. Patients between 3 and 16 years old, diagnosed with cancer and treated with vincristine in two specialized medical centers are asked to participate. Based on statistical estimates, the target enrollment is 40 patients. The intervention includes playing elective active video games and, in addition, education and consultations for the family. The control group will receive a general recommendation for physical activity for 30 minutes per day. The main outcomes are the amount of physical activity and sedentary behavior. Other outcomes include motor performance, fatigue and metabolic risk factors. The outcomes are examined with questionnaires, diaries, physical examinations and blood tests at baseline and at 2, 6, 12 and 30 months after the baseline. Additionally, the children's perceptions of the most enjoyable activation methods are explored through an interview at 2 months. This trial will help to answer the question of whether playing active video games is beneficial for children with cancer. It will also provide further reasoning for physical activity promotion and training of motor skills during treatment. ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012).

The web of clinical trial registration obligations: have foreign clinical trials been caught?

PubMed

Hathaway, Carolyne R; Manthei, John R; Haas, J Ben; Meltzer, Elizabeth D

2009-01-01

The web of overlapping requirements, standards, recommendations and policies governing the conduct of clinical trials highlights the intense scrutiny of the ethical, data quality and public access issues raised by human trials that are conducted to demonstrate the safety and efficacy of medical products marketed in the United States. One relatively recent development is the requirement that sponsors register and make public information about their clinical trials and clinical trial results. These clinical trial registration requirements illustrate the interests of patients, providers and researchers in increased visibility, transparency and accessibility of clinical trials and the data they generate. These requirements, however, pose regulatory, logistical and practical hurdles for companies sponsoring clinical trials of drugs and medical devices.

Clinical Trials - Multiple Languages

MedlinePlus

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

Conducting clinical trials in Singapore.

PubMed

Woo, K T

1999-04-01

All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov

PubMed Central

Huang, Jihan; Li, Jordan V.; Lv, Yinghua; He, Yingchun

2017-01-01

Objective The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. Methods We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Results Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. Conclusion This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM. PMID:29138646

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

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

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.

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2010 CFR

2010-04-01

... clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... and evaluation of clinical trials. For drugs covered under this section, the Commissioner and other agency officials will monitor the progress of the conduct and evaluation of clinical trials and be...

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.

The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C?*.

PubMed

Opal, Steven M; Dellinger, R Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C

2014-07-01

The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. We selected the major clinical studies that investigated interventional trials with novel therapies to treat sepsis over the last 30 years. Phase II and phase III trials investigating new treatments for sepsis and editorials and critiques of these studies. Selected manuscripts and clinical study reports were analyzed from sepsis trials. Specific shortcomings and potential pit falls in preclinical evaluation and clinical study design and analysis were reviewed and synthesized. After review and discussion, a series of 12 recommendations were generated with suggestions to guide future studies with new treatments for sepsis. We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design

A systematic review of measurement of endoscopic disease activity and mucosal healing in Crohn's disease: recommendations for clinical trial design.

PubMed

Khanna, Reena; Bouguen, Guillaume; Feagan, Brian G; DʼHaens, Geert; Sandborn, William J; Dubcenco, Elena; Baker, K Adam; Levesque, Barrett G

2014-10-01

Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials. A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized. The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties. Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

PubMed

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants <18 years old) conducted in South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

Clinical trials involving positron emission tomography and prostate cancer: an analysis of the ClinicalTrials.gov database.

PubMed

Cihoric, Nikola; Vlaskou Badra, Eugenia; Tsikkinis, Alexandros; Prasad, Vikas; Kroeze, Stephanie; Igrutinovic, Ivan; Jeremic, Branislav; Beck, Marcus; Zschaeck, Sebastian; Wust, Peter; Ghadjar, Pirus

2018-06-18

The goal of this study is to evaluate the status and future perspectives of clinical trials on positron emission tomography in prostate cancer for diagnostic or therapeutic as well as for surveillance purposes. The www.ClinicalTrials.gov database was searched on the 20th of January 2017 for all trials containing terms describing "prostate cancer" (prostate, prostatic, malignant, malignancy, cancer, tumor) and "positron emission tomography". In total 167 trials were identified. Trials that included diseases other than PCa were excluded (n = 27; 16%). Furthermore, we excluded trials (n = 4, 2%) withdrawn prior to first patient enrollment. The remaining trials (n = 137, 82%) were selected for further manual classification analysis. One hundred thirty-seven trials were detected and analyzed. Majority of trials were in "active" recruitment status (n = 46, 34%) followed by trials that had been "completed" - (n = 34, 25%) and trials with "closed recruitment but active follow-up" (n = 23, 17%). Phase 1 and 2 comprised 46% of the complete trial portfolio. Locally confined disease was of major interest (n = 46, 34%), followed by metastatic disease - not otherwise specified (n = 43, 13%). Evaluation of PET was the primary goal of the trial in 114 (83%) cases. Most of the trials evaluated only one agent (n = 122, 89%). Choline and PSMA represented two major groups (total 50%) and they were equally distributed across trial portfolio with 25% (n = 34) each. PSMA trials showed the highest average annual growth rate of 56%. The trials were conducted in 17 countries. The scientific community is showing a strong and ever-growing interest in the field and we expect that in the coming years, more phase III trials will be initiated ultimately delivering the required Level 1 evidence.

Ethics of clinical trials.

PubMed

Iyalomhe, G B S; Imomoh, P A

2007-01-01

Although clinical trials are conducted far more ethically and safer now than they were some decades ago, the elimination of gross abuses has tended to highlight more subtle ethical problems. Therefore, research in man, especially clinical drug trials, must now take into account ethical and legal requirements. This review examines the progress of clinical trial ethics, highlights the major ethical principles and challenges involved in the conduct of clinical trials, and suggests measures to ensure scientifically and ethically sound clinical trials. An internet search and a perusal of the literature on the history of clinical trials, medical ethics and good clinical practice, reveal that apart from laying a general principle, the Oath of Hippocrates did not provide a guide on the specific ethical problems involved in undertaking research, an important arm of advancement in medical knowledge. Hence, to avert continued ethical abuses of subjects during clinical research, the current reference guideliNe--the Helsinki Declaration of 1964 (revised in 1975), was adopted by the World Medical Assembly. It emphasized four major principles: autonomy, nonmaleficience, beneficence and justice. In applying these principles, the researcher must obtain a written free and well informed consent from patients who should be aware of their right to withdraw from trial at any moment. Where possible, a new drug should always first be compared to placebo in order to prove its superiority. He must ethically monitor and assess risks and benefits of the trial throughout its duration and use a fair procedure in selecting research subjects and must respect the concept of inviolability of the human person. Ethical challenges confronting clinical trials include the appropriateness of the proposed research, obtaining free informed consent, use of medications after completion of drug trials, drug toxicities and long-term side effects as well as the release and publication of research result. To

Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark.

PubMed

Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

2014-01-01

Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A "single point-of-entry" system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment.

Respiratory Tract Infection Clinical Trials from 2007 to 2012. A Systematic Review of ClinicalTrials.gov.

PubMed

Ruopp, Marcus; Chiswell, Karen; Thaden, Joshua T; Merchant, Kunal; Tsalik, Ephraim L

2015-12-01

Respiratory tract infections are highly prevalent and variable, and confer considerable morbidity and mortality. There is a growing need for new treatments for such infections, particularly in the setting of worsening antibacterial resistance. We analyzed data from ClinicalTrials.gov to summarize activity in respiratory infection trials, identify gaps in research activity, and inform efforts to address disparities between antimicrobial resistance and development of new antibacterial drugs. We examined 69,779 interventional trials registered with ClinicalTrials.gov from 2007 to 2012, focusing on study conditions and interventions to identify respiratory infection-related trials. Programmatic identification with manual confirmation yielded 6,253 infectious disease trials, 1,377 respiratory infection trials, and 270 lower respiratory tract infection trials for analysis. The 1,377 respiratory infection trials accounted for 2% of all trials and 22% of infectious diseases trials. Such trials (54.8%) were more likely than either nonrespiratory infectious diseases trials (48.1%) or noninfectious disease trials (42.8%) to receive industry funding. Stratification of respiratory infection trials by registration year demonstrated declining industry funding: 181 (64.9%) in 2007-2008 to 110 (46.0%) in 2011-2012. Respiratory infection trials more frequently evaluated vaccines (52.7 vs. 15.5% of nonrespiratory tract infection trials). Lower respiratory tract infection trials (excluding tuberculosis) focused primarily on bacterial pathogens (78.5%) followed by viral (12.6%), fungal (5.6%), and nontuberculous mycobacterial (3.0%) pathogens. Approximately 40% of 120 lower respiratory tract infection trials that were completed or terminated published results in the literature. On multivariable logistic regression analysis, a treatment focus was associated with decreased odds of publishing results (odds ratio, 0.28; 95% confidence interval, 0.10-0.82; P = 0.02). There were also

Prevalence of clinical trial status discrepancies: A cross-sectional study of 10,492 trials registered on both ClinicalTrials.gov and the European Union Clinical Trials Register.

PubMed

Fleminger, Jessica; Goldacre, Ben

2018-01-01

Trial registries are a key source of information for clinicians and researchers. While building OpenTrials, an open database of public trial information, we identified errors and omissions in registries, including discrepancies between descriptions of the same trial in different registries. We set out to ascertain the prevalence of discrepancies in trial completion status using a cohort of trials registered on both the European Union Clinical Trials Register (EUCTR) and ClinicalTrials.gov. We used matching titles and registry IDs provided by both registries to build a cohort of dual-registered trials. Completion statuses were compared; we calculated descriptive statistics on the prevalence of discrepancies. 11,988 dual-registered trials were identified. 1,496 did not provide a comparable completion status, leaving 10,492 trials. 16.2% were discrepant on completion status. The majority of discrepancies (90.5%) were a 'completed' trial on ClinicalTrials.gov inaccurately marked as 'ongoing' on EUCTR. Overall, 33.9% of dual-registered trials described as 'ongoing' on EUCTR were listed as 'completed' on ClinicalTrials.gov. Completion status on registries is commonly inaccurate. Previous work on publication bias may underestimate non-reporting. We describe simple steps registry owners and trialists could take to improve accuracy.

Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.

PubMed

Ogutu, Bernhards R; Baiden, Rita; Diallo, Diadier; Smith, Peter G; Binka, Fred N

2010-04-20

The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that

Sustainable development of a GCP-compliant clinical trials platform in Africa: the Malaria Clinical Trials Alliance perspective

PubMed Central

2010-01-01

Background The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Case description Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. Conclusion In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The

Temporal Trends and Predictors for Cancer Clinical Trial Availability for Medically Underserved Populations

PubMed Central

Lakoduk, Ashley M.; Priddy, Laurin L.; Yan, Jingsheng; Xie, Xian-Jin

2015-01-01

Background. Lack of access to available cancer clinical trials has been cited as a key factor limiting trial accrual, particularly among medically underserved populations. We examined the trends and factors in clinical trial availability within a major U.S. safety-net hospital system. Materials and Methods. We identified cancer clinical trials activated at the Harold C. Simmons Cancer from 1991 to 2014 and recorded the characteristics of the trials that were and were not activated at the Parkland Health and Hospital System satellite site. We used univariate and multivariate logistic regression to determine the association between trial characteristics and nonactivation status, and chi-square analysis to determine the association between the trial characteristics and the reasons for nonactivation. Results. A total of 773 trials were identified, of which 152 (20%) were not activated at Parkland. In multivariable analysis, nonactivation at Parkland was associated with trial year, sponsor, and phase. Compared with the 1991–2006 period, clinical trials in the 2007–2014 period were almost eightfold more likely not to be activated at Parkland. The most common reasons for nonactivation at Parkland were an inability to perform the study procedures (27%) and the startup costs (15%). Conclusion. Over time, in this single-center setting, a decreasing proportion of cancer clinical trials were available to underserved populations. Trial complexity and costs appeared to account for much of this trend. Efforts to overcome these barriers will be key to equitable access to clinical trials, efficient accrual, and the generalizability of the results. Implications for Practice: Despite numerous calls to increase and diversify cancer clinical trial accrual, the present study found that cancer clinical trial activation rates in a safety-net setting for medically underserved populations have decreased substantially in recent years. The principal reasons for study nonactivation were

Tools in a clinical information system supporting clinical trials at a Swiss University Hospital.

PubMed

Weisskopf, Michael; Bucklar, Guido; Blaser, Jürg

2014-12-01

hospital admission alerts of trial participants, 107 running trials have activated this option, including 48 out of 97 studies (49.5%) registered in the year 2013, generating approximately 85 alerts per month. The popularity of the presented tools in the clinical information system illustrates their potential to facilitate the conduct of clinical trials. The tools also allow for enhanced transparency on trials conducted at the hospital. Future studies on monitoring and inspection findings will have to evaluate their impact on quality and safety. © The Author(s) 2014.

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.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be

Gene therapy clinical trials worldwide to 2017: An update.

PubMed

Ginn, Samantha L; Amaya, Anais K; Alexander, Ian E; Edelstein, Michael; Abedi, Mohammad R

2018-03-25

To date, almost 2600 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our November 2017 update, we have entries on 2597 trials undertaken in 38 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and the genes that have been transferred. Details of the analyses presented, and our searchable database are available via The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in gene therapy clinical trials around the world, and discuss key trends since the previous review, namely the use of chimeric antigen receptor T cells for the treatment of cancer and advancements in genome editing technologies, which have the potential to transform the field moving forward. Copyright © 2018 John Wiley & Sons, Ltd.

Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department

PubMed Central

Ni, Yizhao; Kennebeck, Stephanie; Dexheimer, Judith W; McAneney, Constance M; Tang, Huaxiu; Lingren, Todd; Li, Qi; Zhai, Haijun; Solti, Imre

2015-01-01

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials. Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed. Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches. Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials. PMID:25030032

Clinical Trials - Information for Participants

MedlinePlus

... Study Near You Learn More Share Clinical Trials – Information for Participants Overview Clinical research trials are at ... improved health in the future. Learn More Contact Information For more information about clinical trials conducted at ...

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

Contribution of clinical trials to gross domestic product in Hungary

PubMed Central

Kaló, Zoltán; Antal, János; Pénzes, Miklós; Pozsgay, Csilla; Szepezdi, Zsuzsanna; Nagyjánosi, László

2014-01-01

Aim To determine the contribution of clinical trials to the gross domestic product (GDP) in Hungary. Methods An anonymous survey of pharmaceutical companies and clinical research organizations (CROs) was conducted to estimate their clinical trial-related employment and revenues. Clinical trial documents at the National Institute of Pharmacy (NIP) were analyzed to estimate trial-related revenues at health care institutions and the value of investigational medical products (IMPs) based on avoided drug costs. Financial benefits were calculated as 2010 US $ purchasing power parity (PPP) values. Results Clinical trials increased the revenue of Hungarian health care providers by US $165.6 million. The value of IMPs was US $67.0 million. Clinical trial operation and management activities generated 900 jobs and US $166.9 million in revenue among CROs and pharmaceutical companies. Conclusions The contribution of clinical trials to the Hungarian GDP in 2010 amounted to 0.2%. Participation in international clinical trials may result in health, financial, and intangible benefits that contribute to the sustainability of health care systems, especially in countries with severe resource constraints. Although a conservative approach was employed to estimate the economic benefits of clinical trials, further research is necessary to improve the generalizability of our findings. PMID:25358877

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

PubMed

Paul, Jisna R; Ranganathan, Prabha

2012-06-01

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.

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. A total of 2367 trials (26.6%) deposited basic summary results within the registry. Of those , 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

Clinical trials finance and operations.

PubMed

O'Brien, Jennifer A

2007-01-01

The National Coverage Decision of 2000 was designed to enhance the participation in clinical trials for both patients and physicians by mandating the governmental coverage for services in a clinical trial that are considered "routine" regardless of the trial. Participation in clinical trials can be a practice builder as well as a contribution to the betterment of medical science. Without proper coverage analysis, study budgeting, accurate time estimates, and effective negotiation prior to signing the contract, participation in clinical trials can cost a practice rather than benefit it.

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics and their Environment

DTIC Science & Technology

2012-07-01

sites to assess their discussions with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about...with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about such trials, and barriers to and...calculated and compared across race/ethnicity. Examination of major outcomes included willingness to participate in, knowledge of, and attitudes towards

Epidemiology of clinical trials of medicines in respiratory diseases in Europe and Italy.

PubMed

Bodini, Roberta; Santus, Pierachille; Di Marco, Fabiano; Aliberti, Stefano; Centanni, Stefano; Blasi, Francesco; Rizzi, Andrea; Recchia, Giuseppe

2017-04-01

Clinical trials play a key role in advancing medical knowledge, improving patient care and promoting economic growth in Europe. We have assessed the clinical trial activity in any respiratory diseases in Europe, with a specific focus on Italy. Information from public sources (EFPIA, clinicaltrials.gov, clinicaltrialsregister. eu, AIFA) was used to describe clinical trial activity of in respiratory diseases in Europe and by country. In 2015, 3908 clinical trials were reported in Europe, 386 in respiratory diseases (9.9%). Germany was the first country both as absolute number (76 trials) and as percentage within country trials (14%), followed by Poland. Spain, Italy and France were the countries with the lowest number and percentage of trials in respiratory diseases. In 2013, the Italian Drug Agency reported 9 trials with respiratory compounds in Italy (2.1% of overall trials, 12ˆ position in the therapeutic area rank), 33% in phase 2 and 66% in phase 3. No phase 1 or phase 4 trials were reported for respiratory trials. Prevalence of respiratory trials by non-profit sponsors (28.3%) was below the average for the country (38.3%). Europe has a greater potential for clinical research on drugs for respiratory diseases, particularly in countries with less activity, such as Spain, France and Italy, that should identify and implement actions to increase attractiveness for clinical trials of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

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. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

[Clinical trials in nursing journals].

PubMed

Di Giulio, Paola; Campagna, Sara; Dimonte, Valerio

2014-01-01

Clinical trials are pivotal for the development of nursing knowledge. To describe the clinical trials published in nursing journals in the last two years and propose some general reflections on nursing research. A search with the key-word trial was done on PubMed (2009-2013) on Cancer Nursing, European Journal of Oncology Nursing, International Journal of Nursing Studies, Journal of Advanced Nursing, Journal of Clinical Nursing and Nursing Research. Of 228 trials identified, 104 (45.8%) were published in the last 2 years. Nurses from Asian countries published the larger number of trials. Educational and supportive interventions were the most studied (61/104 trials), followed by clinical interventions (33/104). Samples were limited and most trials are monocentric. A growing number of trials is published, on issues relevant for the nursing profession, however larger samples and multicentric studies would be necessary.

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.

Review of the registration of clinical trials in UMIN-CTR from 2 June 2005 to 1 June 2010 - focus on Japan domestic, academic clinical trials

PubMed Central

2013-01-01

Background Established on 1 June 2005, the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) is the largest clinical trial registry in Japan, and joined the World Health Organization (WHO) registry network in October 2008. Our aim was to understand the registration trend and overall characteristics of Japan domestic, academic (non-industry-funded) clinical trials, which constitute the main body of registrations in UMIN-CTR. In addition, we aimed to investigate the accessibility of clinical trials in UMIN-CTR to people worldwide, as well as the accessibility of clinical trials conducted in Japan but registered abroad to Japanese people in the Japanese language. Methods We obtained the data for registrations in UMIN-CTR from the UMIN Center, and extracted Japan domestic, academic clinical trials to analyze their registration trend and overall characteristics. We also investigated how many of the trials registered in UMIN-CTR could be accessed from the International Clinical Trials Registry Platform (ICTRP). Finally, we searched ClinicalTrials.gov for all clinical trials conducted in Japan and investigated how many of them were also registered in Japanese registries. All of the above analyses included clinical trials registered from 2 June 2005 to 1 June 2010. Results During the period examined, the registration trend showed an obvious peak around September 2005 and rapid growth from April 2009. Of the registered trials, 46.4% adopted a single-arm design, 34.5% used an active control, only 10.9% were disclosed before trial commencement, and 90.0% did not publish any results. Overall, 3,063 of 3,064 clinical trials registered in UMIN-CTR could be accessed from ICTRP. Only 8.7% of all clinical trials conducted in Japan and registered in ClinicalTrials.gov were also registered in Japanese registries. Conclusions The International Committee of Medical Journal Editors (ICMJE) announcements about clinical trial registration and the Ethical

Informed Consent (Clinical Trials)

MedlinePlus

... Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z List of Cancer ... Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & ...

Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network.

PubMed

Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi

2016-07-11

Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

PubMed

Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

2015-05-01

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Characteristics of clinical trial websites: information distribution between ClinicalTrials.gov and 13 primary registries in the WHO registry network.

PubMed

Ogino, Daisuke; Takahashi, Kunihiko; Sato, Hajime

2014-11-05

It is well known that information about clinical trials is not easily accessible by the public. In Japan, clinical trial information can be accessed by the general public through online registries; however, many people find these registries difficult to use. To improve current clinical trial registries, we propose that combining them with clinical information phrased in lay terms would be beneficial to other interested professionals such as journalists and clinicians, as well as the general public. Therefore, this study aimed to examine the current pattern of distribution of clinical trial information from the primary World Health Organization (WHO) registries. Based on the results of this assessment, we then aimed to build and evaluate a prototype of the Japan Primary Registries Network (JPRN) portal that would be easily accessible to patients and the public, while still remaining useful for professionals. We assessed a total of 14 primary clinical trial registries listed on the WHO International Clinical Trials Registry Platform between January and February 2013. Website content was accessed and checked against a series of items that looked at usability, communication, design and accessibility of the sites. We excluded registries that were not active or were not on the approved WHO registry list at the time of our assessment. We also examined only the English versions of the websites as native-language registries may offer more functionality or different content than the English version of the same website. All registries examined had a function allowing users to search the registry data and that displayed the related information from the search, including the clinical trial registration data. However, few websites were found to be user-friendly, and there was little integration with social media. We confirmed that there are few websites providing useful clinical trial information to patients and their families. However, information gleaned from some of the more

Discrepancies between ClinicalTrials.gov recruitment status and actual trial status: a cross-sectional analysis.

PubMed

Jones, Christopher W; Safferman, Michelle R; Adams, Amanda C; Platts-Mills, Timothy F

2017-10-11

To determine the accuracy of the recruitment status listed on ClinicalTrials.gov as compared with the actual trial status. Cross-sectional analysis. Random sample of interventional phase 2-4 clinical trials registered between 2010 and 2012 on ClinicalTrials.gov. For each trial which was listed within ClinicalTrials.gov as ongoing, two investigators performed a comprehensive literature search for evidence that the trial had actually been completed. For each trial listed as completed or terminated early by ClinicalTrials.gov, we compared the date that the trial was actually concluded with the date the registry was updated to reflect the study's conclusion status. Among the 405 included trials, 92 had a registry status indicating that study activity was either ongoing or the recruitment status was unknown. Of these, published results were available for 34 (37%). Among the 313 concluded trials, the median delay between study completion and a registry update reflecting that the study had ended was 141 days (IQR 48-419), with delays of over 1 year present for 29%. In total, 125 trials (31%) either had a listed recruitment status which was incorrect or had a delay of more than 1 year between the time the study was concluded and the time the registry recruitment status was updated. At present, registry recruitment status information in ClinicalTrials.gov is often outdated or wrong. This inaccuracy has implications for the ability of researchers to identify completed trials and accurately characterise all available medical knowledge on a given subject. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Parents' perceived obstacles to pediatric clinical trial participation: Findings from the clinical trials transformation initiative.

PubMed

Greenberg, Rachel G; Gamel, Breck; Bloom, Diane; Bradley, John; Jafri, Hasan S; Hinton, Denise; Nambiar, Sumathi; Wheeler, Chris; Tiernan, Rosemary; Smith, P Brian; Roberts, Jamie; Benjamin, Daniel K

2018-03-01

Enrollment of children into pediatric clinical trials remains challenging. More effective strategies to improve recruitment of children into trials are needed. This study used in-depth qualitative interviews with parents who were approached to enroll their children in a clinical trial in order to gain an understanding of the barriers to pediatric clinical trial participation. Twenty-four parents whose children had been offered the opportunity to participate in a clinical trial were interviewed: 19 whose children had participated in at least 1 clinical trial and 5 who had declined participation in any trial. Each study aspect, from the initial explanation of the study to the end of the study, can affect the willingness of parents to consent to the proposed study and future studies. Establishing trust, appropriate timing, a transparent discussion of risks and benefits oriented to the layperson, and providing motivation for children to participate were key factors that impacted parents' decisions. In order for clinical trial accrual to be successful, parents' priorities and considerations must be a central focus, beginning with initial trial design. The recommendations from the parents who participated in this study can be used to support budget allocations that ensure adequate training of study staff and improved staffing on nights and weekends. Studies of parent responses in outpatient settings and additional inpatient settings will provide valuable information on the consent process from the child's and parent's perspectives. Further studies are needed to explore whether implementation of such strategies will result in improved recruitment for pediatric clinical trials.

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.

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

PubMed Central

Bothwell, Laura E; Avorn, Jerry; Khan, Nazleen F; Kesselheim, Aaron S

2018-01-01

Objectives This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials. Design Review of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs. Results 142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs. Conclusions Wider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis. PMID:29440155

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mishra, Mark V., E-mail: mmishra@umm.edu; Aggarwal, Sameer; Bentzen, Soren M.

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. Methods and Materials: Active PBT clinical trials were identified from (clinicaltrials.gov) and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% ofmore » trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.« less

Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials.

PubMed

Serebruany, Victor L; Glassman, Alexander H; Malinin, Alex I; Sane, David C; Finkel, Mitchell S; Krishnan, Ranga R; Atar, Dan; Lekht, Vladimir; O'Connor, Christopher M

2003-09-01

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics, and Their Environment

DTIC Science & Technology

2011-07-01

cancer clinical trials, attitudes and knowledge about such trials, and barriers to and facilitators of participation, b) Conduct a self-administered...facilitate or hinder participation in prostate cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of...cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of prostate trials and sites, and broader community

Histone deacetylase inhibitors: current status and overview of recent clinical trials.

PubMed

Ma, Xujun; Ezzeldin, Hany H; Diasio, Robert B

2009-10-01

Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that have a potential role in the regulation of gene expression, induction of cell death, apoptosis and cell cycle arrest of cancer cells by altering the acetylation status of chromatin and other non-histone proteins. In clinical trials, HDAC inhibitors have demonstrated promising antitumour activity as monotherapy in cutaneous T-cell lymphoma and other haematological malignancies. In solid tumours, several HDAC inhibitors have been shown to be efficacious as single agents; however, results of most clinical trials were in favour of using HDAC inhibitors either prior to the initiation of chemotherapy or in combination with other treatments. Currently, the molecular basis of response to HDAC inhibitors in patients is not fully understood. In this review, we summarize the current status of HDAC inhibitors, as single agents or in combination with other agents in different phases of clinical trials. In most of the clinical trials, HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC inhibitors have been studied in phase I, II and III clinical trials with variable efficacy. The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome.

Patient engagement in clinical trials: The Clinical Trials Transformation Initiative's leadership from theory to practical implementation.

PubMed

Patrick-Lake, Bray

2018-02-01

Patient engagement is an increasingly important aspect of successful clinical trials. Over the past decade, as patient group involvement in clinical trials has continued to increase and diversify, the Clinical Trials Transformation Initiative has not only recognized the crucial role patients play in improving the clinical trial enterprise but also made a deep commitment to help grow and shape the emerging field of patient engagement. This article describes the evolution of patient engagement including the origins of the patient engagement movement; barriers to successful engagement and remaining challenges to full and valuable collaboration between patient groups and trial sponsors; and Clinical Trials Transformation Initiative's role in influencing the field through organizational practices, formal project work and resulting recommendations, and external advocacy efforts.

Factors Contributing to Exacerbating Vulnerabilities in Global Clinical Trials

PubMed Central

da Silva, Ricardo E.; Amato, Angélica A.; Guilhem, Dirce B.; de Carvalho, Marta R.; Lima, Elisangela da C.; Novaes, Maria Rita C. G.

2018-01-01

Background: Although policies and guidelines make use of the concept of vulnerability, few define it. The European Union's directive for clinical trials does not include explanations for or the reasoning behind the designation of certain groups as vulnerable. Emerging economies from lower middle-income countries have, in recent years, had the largest average annual growth rate, as well as increase, in number of clinical trials registered in the US government's database. Nevertheless, careful supervision of research activities has to be ensured. Objective: To describe and analyze the features of the clinical trials involving vulnerable populations in various countries classified by development status and geographic region. Methods: Retrospective study that involved analysis of data obtained from the International Clinical Trials Registry Platform (ICTRP) database between 01/2014 and 12/2014 from countries with (i) highest trial densities during 2005 to 2012, (ii) highest average growth rate in clinical trials, and (iii) greatest trial capabilities. Results: Statistical analysis of this study showed that patients incapable of giving consent personally are 11.4 times more likely to be vulnerable patients than patients who are capable, and that patients in upper-middle-income countries are 1.7 times more likely to be vulnerable patients than patients from high-income countries when participating in global clinical trials. Malaysia (21%), Egypt (20%), Turkey (19%), Israel (18%), and Brazil (17%) had the highest percentages of vulnerable populations involving children. Conclusions: Although the inability to provide consent personally was a factor associated with vulnerability, arbitrary criteria may have been considered when classifying the populations of clinical trials as vulnerable. The EU Clinical Trials Register should provide guidance regarding exactly what aspects or factors should be taken into account to frame given populations as vulnerable, because

Factors Contributing to Exacerbating Vulnerabilities in Global Clinical Trials.

PubMed

da Silva, Ricardo E; Amato, Angélica A; Guilhem, Dirce B; de Carvalho, Marta R; Lima, Elisangela da C; Novaes, Maria Rita C G

2017-01-01

Background: Although policies and guidelines make use of the concept of vulnerability, few define it. The European Union's directive for clinical trials does not include explanations for or the reasoning behind the designation of certain groups as vulnerable. Emerging economies from lower middle-income countries have, in recent years, had the largest average annual growth rate, as well as increase, in number of clinical trials registered in the US government's database. Nevertheless, careful supervision of research activities has to be ensured. Objective: To describe and analyze the features of the clinical trials involving vulnerable populations in various countries classified by development status and geographic region. Methods: Retrospective study that involved analysis of data obtained from the International Clinical Trials Registry Platform (ICTRP) database between 01/2014 and 12/2014 from countries with (i) highest trial densities during 2005 to 2012, (ii) highest average growth rate in clinical trials, and (iii) greatest trial capabilities. Results: Statistical analysis of this study showed that patients incapable of giving consent personally are 11.4 times more likely to be vulnerable patients than patients who are capable, and that patients in upper-middle-income countries are 1.7 times more likely to be vulnerable patients than patients from high-income countries when participating in global clinical trials. Malaysia (21%), Egypt (20%), Turkey (19%), Israel (18%), and Brazil (17%) had the highest percentages of vulnerable populations involving children. Conclusions: Although the inability to provide consent personally was a factor associated with vulnerability, arbitrary criteria may have been considered when classifying the populations of clinical trials as vulnerable. The EU Clinical Trials Register should provide guidance regarding exactly what aspects or factors should be taken into account to frame given populations as vulnerable, because

Paying for Clinical Trials

Cancer.gov

Learn about the different types of costs related to taking part in a clinical trial, and who is expected to pay for which costs. This whiteboard animation from the National Cancer Insitute (NCI) is part of a video series about clinical trials.

Biopharmaceutical industry-sponsored global clinical trials in emerging countries.

PubMed

Alvarenga, Lenio Souza; Martins, Elisabeth Nogueira

2010-01-01

To evaluate biopharmaceutical industry-sponsored clinical trials placed in countries previously described as emerging regions for clinical research, and potential differences for those placed in Brazil. Data regarding recruitment of subjects for clinical trials were retrieved from www.clinicaltrials.gov on February 2nd 2009. Proportions of sites in each country were compared among emerging countries. Multiple logistic regressions were performed to evaluate whether trial placement in Brazil could be predicted by trial location in other countries and/or by trial features. A total of 8,501 trials were then active and 1,170 (13.8%) included sites in emerging countries (i.e., Argentina, Brazil, China, Czech Republic, Hungary, India, Mexico, Poland, Russia, South Korea, and South Africa). South Korea and China presented a significantly higher proportion of sites when compared to other countries (p<0.05). Multiple logistic regressions detected no negative correlation between placement in other countries when compared to Brazil. Trials involving subjects with less than 15 years of age, those with targeted recruitment of at least 1,000 subjects, and seven sponsors were identified as significant predictors of trial placement in Brazil. No clear direct competition between Brazil and other emerging countries was detected. South Korea showed the higher proportion of sites and ranked third in total number of trials, appearing as a major player in attractiveness for biopharmaceutical industry-sponsored clinical trials.

Characteristics of oncology clinical trials: insights from a systematic analysis of ClinicalTrials.gov.

PubMed

Hirsch, Bradford R; Califf, Robert M; Cheng, Steven K; Tasneem, Asba; Horton, John; Chiswell, Karen; Schulman, Kevin A; Dilts, David M; Abernethy, Amy P

2013-06-10

Clinical trials are essential to cancer care, and data about the current state of research in oncology are needed to develop benchmarks and set the stage for improvement. To perform a comprehensive analysis of the national oncology clinical research portfolio. All interventional clinical studies registered on ClinicalTrials.gov between October 2007 and September 2010 were identified using Medical Subject Heading terms and submitted conditions. They were reviewed to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. Of 40 970 interventional studies registered between October 2007 and September 2010, a total of 8942 (21.8%) focused on oncology. Compared with other specialties, oncology trials were more likely to be single arm (62.3% vs 23.8%; P < .001), open label (87.8% vs 47.3%; P < .001), and nonrandomized (63.9% vs 22.7%; P < .001). There was moderate but significant correlation between number of trials conducted by cancer type and associated incidence and mortality (Spearman rank correlation coefficient, 0.56 [P = .04] and 0.77 [P = .001], respectively). More than one-third of all oncology trials were conducted solely outside North America. There are significant variations between clinical trials in oncology and other diseases, as well as among trials within oncology. The differences must be better understood to improve both the impact of cancer research on clinical practice and the use of constrained resources.

Building trust and diversity in patient-centered oncology clinical trials: An integrated model.

PubMed

Hurd, Thelma C; Kaplan, Charles D; Cook, Elise D; Chilton, Janice A; Lytton, Jay S; Hawk, Ernest T; Jones, Lovell A

2017-04-01

Trust is the cornerstone of clinical trial recruitment and retention. Efforts to decrease barriers and increase clinical trial participation among diverse populations have yielded modest results. There is an urgent need to better understand the complex interactions between trust and clinical trial participation. The process of trust-building has been a focus of intense research in the business community. Yet, little has been published about trust in oncology clinical trials or the process of building trust in clinical trials. Both clinical trials and business share common dimensions. Business strategies for building trust may be transferable to the clinical trial setting. This study was conducted to understand and utilize contemporary thinking about building trust to develop an Integrated Model of Trust that incorporates both clinical and business perspectives. A key word-directed literature search of the PubMed, Medline, Cochrane, and Google Search databases for entries dated between 1 January 1985 and 1 September 2015 was conducted to obtain information from which to develop an Integrated Model of Trust. Successful trial participation requires both participants and clinical trial team members to build distinctly different types of interpersonal trust to effect recruitment and retention. They are built under conditions of significant emotional stress and time constraints among people who do not know each other and have never worked together before. Swift Trust and Traditional Trust are sequentially built during the clinical trial process. Swift trust operates during the recruitment and very early active treatment phases of the clinical trial process. Traditional trust is built over time and operates during the active treatment and surveillance stages of clinical trials. The Psychological Contract frames the participants' and clinical trial team members' interpersonal trust relationship. The "terms" of interpersonal trust are negotiated through the psychological

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

Inclusion of Minority Patients in Breast Cancer Clinical Trials: The Role of the Clinical Trial Environment

DTIC Science & Technology

2007-05-01

competence of clinical trial staff, and outreach efforts. We have started to geographic, social and physical attributes of the communities surrounding the...aimed at clinical trial sites and that address specific barriers associated with the social or physical environment. 15. SUBJECT TERMS Clinical trials...and availability of trials, patient burden and benefit, site cultural competence, and outreach efforts. We will also examine the social and

Types of Cancer Clinical Trials

Cancer.gov

Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.

Dialogues on Diversifying Clinical Trials: Successful Strategies for Engaging Women and Minorities in Clinical Trials

PubMed Central

Fadiran, Emmanuel Olutayo; Parrish, L. Jo; Griffith, Rachel A.; Weiss, Eleanor; Carter, Christine

2012-01-01

Abstract There is mounting scientific evidence pointing to genetic or physiologic distinctions between genders and among racial and ethnic groups that influence disease risk and severity and response to treatment. The diverse enrollment of subjects engaged in clinical trials research is, thus, critical to developing safer and more effective drugs and medical devices. However, in the United States, there are striking disparities in clinical trial participation. To address this problem, the Food and Drug Administration (FDA) Office of Women's Health and the Society for Women's Health Research (SWHR) together convened the 2-day meeting, Dialogues on Diversifying Clinical Trials. The conference was held in Washington, DC, on September 22–23, 2011, and brought together a wide range of speakers from clinical research, industry, and regulatory agencies. Here, we present the major findings discussed at this meeting about female and minority patients and physicians and their willingness to participate in clinical trials and the barriers that sponsors face in recruiting a diverse trial population. We also discuss some recommendations for improving trial diversity through new technologies and greater efficiency in trial regulation and review. PMID:22747427

Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

PubMed

Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

2016-06-01

Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

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

Optimizing biologically targeted clinical trials for neurofibromatosis

PubMed Central

Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J

2014-01-01

Introduction The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Areas covered Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. Expert opinion The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy. PMID:23425047

[Establishing the acupuncture-moxibustion clinical trial registry and improving the transparence of clinical trials of acupuncture and moxibustion].

PubMed

Liu, Yali; He, Liyun; Liu, Jia; Yang, Xingyue; Yan, Dongning; Wang, Xin; Luo, Lin; Li, Hongjiao; Yan, Shiyan; Wen, Tiancai; Bai, Wenjing; Wu, Taixiang; Liu, Baoyan

2017-07-12

As a kind of intervention measures of traditional Chinese medicine, acupuncture-moxibustion is highly adopted on global clinical practice. Even though the global clinical trial registration system was established more than 10 years ago, the proportion of acupuncture-moxibustion clinical trial registration is still very low; and it is very problematic on the methodological quality and report quality in the published acupuncture-moxibustion clinical trials. In order to manage particularly the acupuncture-moxibustion clinical trials, China Academy of Chinese Medical Sciences, collaborated with China Association of Acupuncture and Moxibustion and World Federation of Acupuncture Societies, established the Acupuncture-Moxibustion Clinical Trail Registry (AMCTR). AMCTR is a secondary registry platform affiliated to the Chinese Clinical Trial Registry (ChiCTR) and WHO International Clinical Trials Registry Platform (ICTRP), specifically for the acceptance and management of clinical trials in the field of acupuncture and moxibustion. It is a nonprofit academic organization, located in China Academy of Chinese Medical Sciences.

Clinical trials. A pending subject.

PubMed

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

2018-04-01

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.

Women in Clinical Trials

MedlinePlus

... your healthcare provider if a clinical trial is right for you. Are Women in Clinical Trials? Yes. Women are already in ... how drugs and devices work. FDA Office of Women’s ... should not feel pressured to join. You have the right to quit at any time. There are rules ...

The costs associated with adverse event procedures for an international HIV clinical trial determined by activity-based costing.

PubMed

Chou, Victoria B; Omer, Saad B; Hussain, Hamidah; Mugasha, Christine; Musisi, Maria; Mmiro, Francis; Musoke, Philippa; Jackson, J Brooks; Guay, Laura A

2007-12-01

To determine costs for adverse event (AE) procedures for a large HIV perinatal trial by analyzing actual resource consumption using activity-based costing (ABC) in an international research setting. The AE system for an ongoing clinical trial in Uganda was evaluated using ABC techniques to determine costs from the perspective of the study. Resources were organized into cost categories (eg, personnel, patient care expenses, laboratory testing, equipment). Cost drivers were quantified, and unit cost per AE was calculated. A subset of time and motion studies was performed prospectively to observe clinic personnel time required for AE identification. In 18 months, there were 9028 AEs, with 970 (11%) reported as serious adverse events. Unit cost per AE was $101.97. Overall, AE-related costs represented 32% ($920,581 of $2,834,692) of all study expenses. Personnel ($79.30) and patient care ($11.96) contributed the greatest proportion of component costs. Reported AEs were predominantly nonserious (mild or moderate severity) and unrelated to study drug(s) delivery. Intensive identification and management of AEs to conduct clinical trials ethically and protect human subjects require expenditure of substantial human and financial resources. Better understanding of these resource requirements should improve planning and funding of international HIV-related clinical trials.

Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

PubMed

Hindryckx, Pieter; Levesque, Barrett G; Holvoet, Tom; Durand, Serina; Tang, Ceen-Ming; Parker, Claire; Khanna, Reena; Shackelton, Lisa M; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Lebwohl, Benjamin; Leffler, Daniel A; Jairath, Vipul

2018-01-01

Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The mPED randomized controlled clinical trial: applying mobile persuasive technologies to increase physical activity in sedentary women protocol

PubMed Central

2011-01-01

Background Despite the significant health benefits of regular physical activity, approximately half of American adults, particularly women and minorities, do not meet the current physical activity recommendations. Mobile phone technologies are readily available, easily accessible and may provide a potentially powerful tool for delivering physical activity interventions. However, we need to understand how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women. The purpose of this paper is to describe the study design and protocol of the mPED (mobile phone based physical activity education) randomized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions. Methods A randomized controlled trial (RCT) with three arms; 1) PLUS (3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention), 2) REGULAR (3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention), and 3) CONTROL (pedometer only, but no intervention will be conducted). A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be randomized into one of the three groups. The mobile phone serves as a means of delivering the physical activity intervention, setting individualized weekly physical activity goals, and providing self-monitoring (activity diary), immediate feedback and social support. The mobile phone also functions as a tool for communication and real-time data capture. The primary outcome is objectively measured physical activity. Discussion If efficacy of the intervention with a mobile phone is demonstrated, the results of this RCT will be able to provide new insights for current behavioral sciences and m

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.

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

The National Clinical Trials Network: Conducting Successful Clinical Trials of New Therapies for Rare Cancers

PubMed Central

Schott, Anne F.; Welch, John J.; Verschraegen, Claire F.; Kurzrock, Razelle

2015-01-01

Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer-related deaths in the United States. However, rare cancers show some of the highest response rates to targeted therapies, probably due to identification of oncogenic drivers with little inter-patient variability. Although the low incidence of rare cancers make large scale randomized trials involving single histologies difficult to perform, drugs have been successfully developed in rare cancers utilizing clinical trial designs that combine microscopic anatomies. Such trials are being pursued within the National Clinical Trials Network (NCTN), which possesses unique qualifications to perform widespread molecular screening of tumors for patient enrollment onto therapeutic clinical trials. When larger clinical trials are needed to determine optimum treatment strategies in rare cancers, the NCTN's broad reach in North America and internationally, and ability to partner with both US-based and international research organizations, can make these challenging studies feasible. PMID:26433554

[Maraviroc: clinical trials results].

PubMed

Chidiac, C; Katlama, C; Yeni, P

2008-03-01

Just over a decade after identification of chemokine receptors CCR5 and CXCR4 as coreceptors for HIV, maraviroc (Celsentri), the first CCR5 antagonist, has recently obtained its Marketing Authorization in the United States and Europe, for treatment of treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable. CCR5 antagonists, after fusion inhibitor enfuvirtide available since 2003, also belong to entry inhibitors. These molecules, unlike previous antiretrovirals, do not target the virus but its target cell by blocking viral penetration. Maraviroc has shown its clinical efficacy in patients failing other antiretroviral classes. Its safety profile was similar to placebo in two large phase III trials. However, careful assessment of both hepatic and immunologic safety of this new therapeutic class is needed. Viral tropism testing has to be investigated before using maraviroc in the clinic, because CCR5 antagonists are not active against CXCR4 viruses. For the moment indicated for the treatment-experienced patient population, maraviroc could in the future benefit to other types of patients, depending on ongoing trials results.

Awareness and attitudes towards clinical trials among Polish oncological patients who had never participated in a clinical trial.

PubMed

Staniszewska, Anna; Lubiejewska, Adriana; Czerw, Aleksandra; Dąbrowska-Bender, Marta; Duda-Zalewska, Aneta; Olejniczak, Dominik; Juszczyk, Grzegorz; Bujalska-Zadrożny, Magdalena

2018-03-21

Participation in a clinical trial significantly shortens waiting time associated with receiving specialist care. Furthermore, it may be the case that, through clinical trials, subjects can access medicines that are not typically available in Poland. The aim of this study was to determine the opinions of oncological patients about clinical trials. The research has been carried out during the years 2014-2016. A proprietary questionnaire consisting of 10 closed, single and multiple choice questions about awareness and perceptions of clinical trials, and 5 questions concerning demographic information was used. A group of 256 patients with cancer (54% women, 46% men), aged 21-77 years, was surveyed. Respondents were statistically more likely to decide to participate in a clinical trial as oncological patients than the healthy volunteers (Pearson's χ2 test p = 0.00006). The desire to qualify for clinical trials in no way depends on the knowledge of side effects (Pearson's χ2 test p = 0.16796). Our study found that the patients' awareness about clinical trials varied. However, a positive attitude towards research was visible. The main identified barriers to clinical trial participation were fear of possible side effects. Most patients regarded clinical trials as useful, and considered that they are conducted to introduce new treatment/new drug.

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.

Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

PubMed Central

Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

2013-01-01

Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

Feasibility of feature-based indexing, clustering, and search of clinical trials. A case study of breast cancer trials from ClinicalTrials.gov.

PubMed

Boland, M R; Miotto, R; Gao, J; Weng, C

2013-01-01

When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.

Patient reported outcomes (PROs) in clinical trials: is 'in-trial' guidance lacking? a systematic review.

PubMed

Kyte, Derek G; Draper, Heather; Ives, Jonathan; Liles, Clive; Gheorghe, Adrian; Calvert, Melanie

2013-01-01

Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on 'in-trial' activity (recruitment, data collection and data inputting) and the management of 'concerning' PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas. Systematic review of 1,362 articles identified 18 eligible papers containing 'in-trial' guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86-0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with 'pre-trial' activities (72%), for example, outcome measure selection and study design issues, or 'post-trial' activities (16%) such as data analysis, reporting and interpretation. 'In-trial' guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data. The findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection.

Managing multicentre clinical trials with open source.

PubMed

Raptis, Dimitri Aristotle; Mettler, Tobias; Fischer, Michael Alexander; Patak, Michael; Lesurtel, Mickael; Eshmuminov, Dilmurodjon; de Rougemont, Olivier; Graf, Rolf; Clavien, Pierre-Alain; Breitenstein, Stefan

2014-03-01

Multicentre clinical trials are challenged by high administrative burden, data management pitfalls and costs. This leads to a reduced enthusiasm and commitment of the physicians involved and thus to a reluctance in conducting multicentre clinical trials. The purpose of this study was to develop a web-based open source platform to support a multi-centre clinical trial. We developed on Drupal, an open source software distributed under the terms of the General Public License, a web-based, multi-centre clinical trial management system with the design science research approach. This system was evaluated by user-testing and well supported several completed and on-going clinical trials and is available for free download. Open source clinical trial management systems are capable in supporting multi-centre clinical trials by enhancing efficiency, quality of data management and collaboration.

Results of an Oncology Clinical Trial Nurse Role Delineation Study.

PubMed

Purdom, Michelle A; Petersen, Sandra; Haas, Barbara K

2017-09-01

To evaluate the relevance of a five-dimensional model of clinical trial nursing practice in an oncology clinical trial nurse population. 
. Web-based cross-sectional survey.
. Online via Qualtrics.
. 167 oncology nurses throughout the United States, including 41 study coordinators, 35 direct care providers, and 91 dual-role nurses who provide direct patient care and trial coordination.
. Principal components analysis was used to determine the dimensions of oncology clinical trial nursing practice.
. Self-reported frequency of 59 activities.
. The results did not support the original five-dimensional model of nursing care but revealed a more multidimensional model.
. An analysis of frequency data revealed an eight-dimensional model of oncology research nursing, including care, manage study, expert, lead, prepare, data, advance science, and ethics.
. This evidence-based model expands understanding of the multidimensional roles of oncology nurses caring for patients with cancer enrolled in clinical trials.

Progress in defining clinically meaningful changes for clinical trials in nonrenal manifestations of SLE disease activity.

PubMed

Choi, Chan-Bum; Liang, Matthew H; Bae, Sang-Cheol

2016-01-06

Since the 2002 Dusseldorf meeting, one new agent, Benlysta, has been approved by the US Food and Drug Administration for systemic lupus erythematosus. Experiences from the field in conducting trials of all the agents tested during this period have provided valuable practical insights. There has been incremental progress in defining the minimal clinically important difference (MCID) of key disease manifestations and the view is largely that of the health care providers and not that of the person suffering the disease. This basic methodological work on the MCID should improve the efficiency and the clinical relevance of future trials and their design.

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.

The Role of Oncology Nurses in Discussing Clinical Trials.

PubMed

Flocke, Susan A; Antognoli, Elizabeth; Daly, Barbara J; Jackson, Brigid; Fulton, Sarah E; Liu, Tasnuva M; Surdam, Jessica; Manne, Sharon; Meropol, Neal J

2017-09-01

To describe oncology nurses' experiences discussing clinical trials with their patients, and to assess barriers to these discussions.
. A qualitative study designed to elicit narratives from oncology nurses. 
. Community- and academic-based oncology clinics throughout the United States.
. 33 oncology nurses involved in direct patient care in community-based and large hospital-based settings. The sample was drawn from members of the Oncology Nursing Society. 
. In-depth interviews were conducted and analyzed using a 
immersion/crystallization approach to identify themes and patterns. The analyses highlight specific issues, examples, and contexts that present challenges to clinical trial discussions with patients.
. Oncology nurses view their roles as patient educators and advocates to be inclusive of discussion of clinical trials. Barriers to such discussions include lack of knowledge and strategies for addressing patients' common misconceptions and uncertainty about the timing of discussions.
. These data indicate that enabling nurses to actively engage patients in discussions of clinical trials requires educational interventions to build self-efficacy and close knowledge gaps. 
. Oncology nurses can play a critical role in advancing cancer care by supporting patients in decision making about clinical trial participation. This will require training and education to build their knowledge, reduce barriers, and increase their self-efficacy to fulfill this responsibility in various clinical settings.

Challenges and opportunities in SLE clinical trials.

PubMed

van Vollenhoven, Ronald F

2013-09-01

To provide an update on the field of clinical trials in systemic lupus erythematosus (SLE). This review will examine failed and successful clinical trials in SLE in order to draw lessons and determine the optimal ways forward. Over the past decade, many clinical trials in SLE met with limited success, but in the past 2 years several SLE clinical trials have been successful. The two large phase III randomized controlled trials (RCTs) of belimumab achieved their primary endpoints and resulted in food and drug administration and European medicines agency approval of the drug. Characteristics of these trials were, among other things, a very large number of patients (>800 each), compound clinical endpoints, and a flexible design with regards to concomitant medication use. Likewise, large randomized controlled trials with mycophenolate mofetil, although nominally unsuccessful, clearly demonstrated the clinical benefit of this drug in lupus nephritis. Posthoc analyses of several failed trials involving abatacept and rituximab revealed design elements and/or outcomes that might have changed the outcomes of these studies. Many smaller trials have also been reported, in some instances with surprisingly positive results. An improved understanding of specific design features in SLE clinical trials combined with robust outcomes will make it possible more effectively to design and conduct clinical trials in SLE.

From clinical trial to prescription.

PubMed

Carpenter, William T

2002-03-01

There are many steps between drug discovery and prescribing for a patient. Each step has problems. In this issue of ARCHIVES, Klein and colleagues propose changes in clinical trials that would result in more meaningful information for the treating physician. Of particular importance is the gap between what a physician needs to know and what is produced in the clinical trials that leads to approval of a new drug by the US Food and Drug Administration (FDA). Their recommendations for improving clinical trials are cogent, but broad-based implementation depends on an organizational structure and political effectiveness not presently in place. Most important, as the authors note, is an effective work group representing industry, regulatory agencies, and academic and federal science, addressing clinical trials issues with public participation. While improved quality and relevance of data from clinical trials will strengthen the scientific foundation of pharmacotherapy, other problems impede the delivery of objective information to the treating physician. Most hotly debated is the role of money in the creation and dissemination of knowledge.

Mortality Rates Among Substance Use Disorder Participants in Clinical Trials: Pooled Analysis of Twenty-Two Clinical Trials Within the National Drug Abuse Treatment Clinical Trials Network.

PubMed

Lindblad, Robert; Hu, Lian; Oden, Neal; Wakim, Paul; Rosa, Carmen; VanVeldhuisen, Paul

2016-11-01

Most substance use disorders (SUD) treatment clinical trials are too short and small to reliably estimate the incidence of rare events like death. The aim of this study is to estimate the overall mortality rates among a SUD treatment-seeking population by pooling participants from multiple clinical trials conducted through the National Institute on Drug Abuse (NIDA)-sponsored National Drug Abuse Treatment Clinical Trials Network (CTN). Drug and or alcohol users (N=9866) who sought treatment and participated in one of the twenty-two CTN trials. Data were collected through randomized clinical trials in national community treatment programs for SUD. Pooled analysis was performed to assess age- and gender-standardized mortality rate(s) (SM rate(s)), and mortality ratio(s) (SM ratio(s)) of CTN trial participants compared to the U.S. general population. The age- and gender-SM rate among CTN trials participants was 1403 (95% CI: 862-2074) per 100,000 person years (PY) compared to 542 (95% CI: 541-543) per 100,000 PY among the U.S. general population in 2005. By gender, age-adjusted SM ratio for female CTN trial participants was over five times (SM ratio=5.35, 95% CI: 3.31-8.19)), and for male CTN trial participants, it was over three times (SM ratio=3.39, 95% CI: 2.25-4.90) higher than their gender comparable peers in the U.S. general population. Age and gender-standardized mortality rates and ratios among NIDA CTN SUD treatment-seeking clinical trial participants are higher than the age and gender comparable U.S. general population. The overall mortality rates of CTN trial participants are similar to in-treatment mortality reported in large U.S. and non-U.S. cohorts of opioid users. Future analysis with additional CTN trial participants and risk times will improve the stability of estimates, especially within subgroups based on primary substance of abuse. These SUD mortality rates can be used to facilitate safety monitoring within SUD clinical trials. Copyright © 2016

The EXCITE Trial: Predicting a Clinically Meaningful Motor Activity Log Outcome

PubMed Central

Park, Si-Woon; Wolf, Steven L.; Blanton, Sarah; Winstein, Carolee; Nichols-Larsen, Deborah S.

2013-01-01

Background and Objective This study determined which baseline clinical measurements best predicted a predefined clinically meaningful outcome on the Motor Activity Log (MAL) and developed a predictive multivariate model to determine outcome after 2 weeks of constraint-induced movement therapy (CIMT) and 12 months later using the database from participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial. Methods A clinically meaningful CIMT outcome was defined as achieving higher than 3 on the MAL Quality of Movement (QOM) scale. Predictive variables included baseline MAL, Wolf Motor Function Test (WMFT), the sensory and motor portion of the Fugl-Meyer Assessment (FMA), spasticity, visual perception, age, gender, type of stroke, concordance, and time after stroke. Significant predictors identified by univariate analysis were used to develop the multivariate model. Predictive equations were generated and odds ratios for predictors were calculated from the multivariate model. Results Pretreatment motor function measured by MAL QOM, WMFT, and FMA were significantly associated with outcome immediately after CIMT. Pretreatment MAL QOM, WMFT, proprioception, and age were significantly associated with outcome after 12 months. Each unit of higher pretreatment MAL QOM score and each unit of faster pretreatment WMFT log mean time improved the probability of achieving a clinically meaningful outcome by 7 and 3 times at posttreatment, and 5 and 2 times after 12 months, respectively. Patients with impaired proprioception had a 20% probability of achieving a clinically meaningful outcome compared with those with intact proprioception. Conclusions Baseline clinical measures of motor and sensory function can be used to predict a clinically meaningful outcome after CIMT. PMID:18780883

The EXCITE Trial: Predicting a clinically meaningful motor activity log outcome.

PubMed

Park, Si-Woon; Wolf, Steven L; Blanton, Sarah; Winstein, Carolee; Nichols-Larsen, Deborah S

2008-01-01

This study determined which baseline clinical measurements best predicted a predefined clinically meaningful outcome on the Motor Activity Log (MAL) and developed a predictive multivariate model to determine outcome after 2 weeks of constraint-induced movement therapy (CIMT) and 12 months later using the database from participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial. A clinically meaningful CIMT outcome was defined as achieving higher than 3 on the MAL Quality of Movement (QOM) scale. Predictive variables included baseline MAL, Wolf Motor Function Test (WMFT), the sensory and motor portion of the Fugl-Meyer Assessment (FMA), spasticity, visual perception, age, gender, type of stroke, concordance, and time after stroke. Significant predictors identified by univariate analysis were used to develop the multivariate model. Predictive equations were generated and odds ratios for predictors were calculated from the multivariate model. Pretreatment motor function measured by MAL QOM, WMFT, and FMA were significantly associated with outcome immediately after CIMT. Pretreatment MAL QOM, WMFT, proprioception, and age were significantly associated with outcome after 12 months. Each unit of higher pretreatment MAL QOM score and each unit of faster pretreatment WMFT log mean time improved the probability of achieving a clinically meaningful outcome by 7 and 3 times at posttreatment, and 5 and 2 times after 12 months, respectively. Patients with impaired proprioception had a 20% probability of achieving a clinically meaningful outcome compared with those with intact proprioception. Baseline clinical measures of motor and sensory function can be used to predict a clinically meaningful outcome after CIMT.

The current status of clinical trials focusing on nasopharyngeal carcinoma: A comprehensive analysis of ClinicalTrials.gov database.

PubMed

Peng, Hao; Chen, Lei; Chen, Yu-Pei; Li, Wen-Fei; Tang, Ling-Long; Lin, Ai-Hua; Sun, Ying; Ma, Jun

2018-01-01

Clinical Trials have emerged as the main force in driving the development of medicine. However, little is known about the current status of clinical trials regarding nasopharyngeal carcinoma (NPC). This study aimed at providing a comprehensive landscape of NPC-related trials on the basis of ClinicalTrials.gov database. We used the keyword "nasopharyngeal carcinoma" to search the ClinicalTrials.gov database and assessed the characteristics of these trials. Up to December 30, 2016, 462 eligible trials in total were identified, of which 222 (48.0%) recruited only NPC (NPC trials) and the other 240 (52.0%) recruited both NPC and other cancers (multiple cancer trials). Moreover, 47 (10.2%) were Epstein-Barr virus (EBV)-related trials and 267 (57.8%) focused on metastatic/recurrent disease. Compared with NPC trials, the multiple cancer trials had a higher percentage of phase 1 (26.7% vs. 6.7%, P < 0.001) studies and more patients with metastatic/recurrent disease (72.5% vs. 41.9%, P < 0.001). Notably, non-EBV trials had more phase 2 or 3 (78.4% vs. 48.8%, P < 0.001) and interventional studies (89.5% vs. 70.7%, P = 0.002) than EBV trials. Obviously, more phase 2/3 or 3 trials were conducted in patients with non-metastatic/recurrent disease (29.4% vs. 4.9%, P < 0.001); however, metastatic/recurrent trials were more likely to be anticancer (94.6% vs. 63.6%, P < 0.001). The role of plasma EBV DNA in clinical trials is underestimated, and high-level randomized clinical trials should be performed for patients with metastatic/recurrent disease.

Types of Treatment: Clinical Trials

MedlinePlus

... or kidney disease Who's on the Clinical Trial Team? A clinical trial team is made up of doctors, nurses, social workers and other healthcare professionals. The team members: Check each participant's health at the beginning ...

Barriers to the conduct of randomised clinical trials within all disease areas.

PubMed

Djurisic, Snezana; Rath, Ana; Gaber, Sabrina; Garattini, Silvio; Bertele, Vittorio; Ngwabyt, Sandra-Nadia; Hivert, Virginie; Neugebauer, Edmund A M; Laville, Martine; Hiesmayr, Michael; Demotes-Mainard, Jacques; Kubiak, Christine; Jakobsen, Janus C; Gluud, Christian

2017-08-01

Randomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers. We performed systematic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. The following barriers to randomised clinical trials were identified: inadequate knowledge of clinical research and trial methodology; lack of funding; excessive monitoring; restrictive privacy law and lack of transparency; complex regulatory requirements; and inadequate infrastructures. There is a need for more pragmatic randomised clinical trials conducted with low risks of systematic and random errors, and multinational cooperation is essential. The present paper presents major barriers to randomised clinical trials. It also underlines the value of using a pan-European-distributed infrastructure to help investigators overcome barriers for multi-country trials in any disease area.

Prevalence of primary outcome changes in clinical trials registered on ClinicalTrials.gov: a cross-sectional study.

PubMed

Ramagopalan, Sreeram; Skingsley, Andrew P; Handunnetthi, Lahiru; Klingel, Michelle; Magnus, Daniel; Pakpoor, Julia; Goldacre, Ben

2014-01-01

An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor. A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Our analysis showed that 28229 of 89204 (31.7%) registered studies had their primary outcome changed.  Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p<0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p<0.001.  Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.

Improving clinical trials in the critically ill.

PubMed

Angus, Derek C; Mira, Jean-Paul; Vincent, Jean-Louis

2010-02-01

To propose ways in which clinical trials in intensive care can be improved. An international roundtable conference was convened focused on improvement in three broad areas: translation of new knowledge from bench to bedside; design and conduct of clinical trials; and clinical trial infrastructure and environment. The roundtable recommendations were: improvement in clinical trials is a multistep process from better preclinical studies to better clinical trial methodology; new technologies should be used to improve models of critical illness; diseasomes and theragnostics will aid inpatient population selection and more appropriate targeting of interventions; broader study end points should include morbidity as well as mortality; more multicenter studies should be conducted by national and international networks or clinical trials groups; and better collaboration is needed with the industry. There was broad agreement among the roundtable participants regarding a number of explicit opportunities for the improvement of clinical trials in critical care.

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

PubMed

Huang, Grant D; Bull, Jonca; Johnston McKee, Kelly; Mahon, Elizabeth; Harper, Beth; Roberts, Jamie N

2018-03-01

Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical Trials

MedlinePlus

... pill that has no medicine in it. Most times participants do not know which they are receiving. Other clinical trials involve a crossover design, where participants are randomly assigned to take a ...

Outcome measurement in clinical trials for Ulcerative Colitis: towards standardisation

PubMed Central

Cooney, Rachel M; Warren, Bryan F; Altman, Douglas G; Abreu, Maria T; Travis, Simon PL

2007-01-01

Clinical trials on novel drug therapies require clear criteria for patient selection and agreed definitions of disease remission. This principle has been successfully applied in the field of rheumatology where agreed disease scoring systems have allowed multi-centre collaborations and facilitated audit across treatment centres. Unfortunately in ulcerative colitis this consensus is lacking. Thirteen scoring systems have been developed but none have been properly validated. Most trials choose different endpoints and activity indices, making comparison of results from different trials extremely difficult. International consensus on endoscopic, clinical and histological scoring systems is essential as these are the key components used to determine entry criteria and outcome measurements in clinical trials on ulcerative colitis. With multiple new therapies under development, there is a pressing need for consensus to be reached. PMID:17592647

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

Physical activity monitoring in adolescents with juvenile fibromyalgia: findings from a clinical trial of cognitive-behavioral therapy.

PubMed

Kashikar-Zuck, Susmita; Flowers, Stacy R; Strotman, Daniel; Sil, Soumitri; Ting, Tracy V; Schikler, Kenneth N

2013-03-01

Juvenile fibromyalgia (JFM) is a chronic musculoskeletal pain condition that is associated with reduced physical function. Recent research has demonstrated that cognitive-behavioral therapy (CBT) is effective in improving daily functioning among adolescents with JFM. However, it is not known whether these improvements were accompanied by increased physical activity levels. Our objective was to analyze secondary data from a randomized clinical trial of CBT to examine whether CBT was associated with improvement in objectively measured physical activity and whether actigraphy indices corresponded with self-reported functioning among adolescents with JFM. Participants were 114 adolescents (ages 11-18 years) recruited from pediatric rheumatology clinics that met criteria for JFM and were enrolled in a clinical trial. Subjects were randomly (1:1) assigned to receive either CBT or fibromyalgia education (FE). Participants wore a hip-mounted accelerometer for 1 week as part of their baseline and posttreatment assessments. The final sample included 68 subjects (94% female, mean age 15.2 years) for whom complete actigraphy data were obtained. Actigraphy measures were not found to correspond with self-reported improvements in functioning. While self-reported functioning improved in the CBT condition compared to FE, no significant changes were seen in either group for activity counts, sedentary, moderate, or vigorous activity. The CBT group had significantly lower peak and light activity at posttreatment. Actigraphy monitoring provides a unique source of information about patient outcomes. CBT intervention was not associated with increased physical activity in adolescents with JFM, indicating that combining CBT with interventions to increase physical activity may enhance treatment effects. Copyright © 2013 by the American College of Rheumatology.

Resource implications of preparing individual participant data from a clinical trial to share with external researchers.

PubMed

Tudur Smith, Catrin; Nevitt, Sarah; Appelbe, Duncan; Appleton, Richard; Dixon, Pete; Harrison, Janet; Marson, Anthony; Williamson, Paula; Tremain, Elizabeth

2017-07-17

Demands are increasingly being made for clinical trialists to actively share individual participant data (IPD) collected from clinical trials using responsible methods that protect the confidentiality and privacy of clinical trial participants. Clinical trialists, particularly those receiving public funding, are often concerned about the additional time and money that data-sharing activities will require, but few published empirical data are available to help inform these decisions. We sought to evaluate the activity and resources required to prepare anonymised IPD from a clinical trial in anticipation of a future data-sharing request. Data from two UK publicly funded clinical trials were used for this exercise: 2437 participants with epilepsy recruited from 90 hospital outpatient clinics in the SANAD trial and 146 children with neuro-developmental problems recruited from 18 hospitals in the MENDS trial. We calculated the time and resources required to prepare each anonymised dataset and assemble a data pack ready for sharing. The older SANAD trial (published 2007) required 50 hours of staff time with a total estimated associated cost of £3185 whilst the more recently completed MENDS trial (published 2012) required 39.5 hours of staff time with total estimated associated cost of £2540. Clinical trial researchers, funders and sponsors should consider appropriate resourcing and allow reasonable time for preparing IPD ready for subsequent sharing. This process would be most efficient if prospectively built into the standard operational design and conduct of a clinical trial. Further empirical examples exploring the resource requirements in other settings is recommended. SANAD: International Standard Randomised Controlled Trials Registry: ISRCTN38354748 . Registered on 25 April 2003. EU Clinical Trials Register Eudract 2006-004025-28 . Registered on 16 May 2007. International Standard Randomised Controlled Trials Registry: ISRCTN05534585 /MREC 07/MRE08

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.

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

Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings.

PubMed

Epperson, C Neill; Terman, Michael; Terman, Jiuan Su; Hanusa, Barbara H; Oren, Dan A; Peindl, Kathleen S; Wisner, Katherine L

2004-03-01

Bright light therapy was shown to be a promising treatment for depression during pregnancy in a recent open-label study. In an extension of this work, we report findings from a double-blind placebo-controlled pilot study. Ten pregnant women with DSM-IV major depressive disorder were randomly assigned from April 2000 to January 2002 to a 5-week clinical trial with either a 7000 lux (active) or 500 lux (placebo) light box. At the end of the randomized controlled trial, subjects had the option of continuing in a 5-week extension phase. The Structured Interview Guide for the Hamilton Depression Scale-Seasonal Affective Disorder Version was administered to assess changes in clinical status. Salivary melatonin was used to index circadian rhythm phase for comparison with antidepressant results. Although there was a small mean group advantage of active treatment throughout the randomized controlled trial, it was not statistically significant. However, in the longer 10-week trial, the presence of active versus placebo light produced a clear treatment effect (p =.001) with an effect size (0.43) similar to that seen in antidepressant drug trials. Successful treatment with bright light was associated with phase advances of the melatonin rhythm. These findings provide additional evidence for an active effect of bright light therapy for antepartum depression and underscore the need for an expanded randomized clinical trial.

The quality of registration of clinical trials.

PubMed

Viergever, Roderik F; Ghersi, Davina

2011-02-24

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. 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. 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.

Standards for gene therapy clinical trials based on pro-active risk assessment in a London NHS Teaching Hospital Trust.

PubMed

Bamford, K B; Wood, S; Shaw, R J

2005-02-01

Conducting gene therapy clinical trials with genetically modified organisms as the vectors presents unique safety and infection control issues. The area is governed by a range of legislation and guidelines, some unique to this field, as well as those pertinent to any area of clinical work. The relevant regulations covering gene therapy using genetically modified vectors are reviewed and illustrated with the approach taken by a large teaching hospital NHS Trust. Key elements were Trust-wide communication and involvement of staff in a pro-active approach to risk management, with specific emphasis on staff training and engagement, waste management, audit and record keeping. This process has led to the development of proposed standards for clinical trials involving genetically modified micro-organisms.

Mortality Rates among Substance Use Disorder Participants in Clinical Trials: Pooled Analysis of Twenty-two Clinical Trials within the National Drug Abuse Treatment Clinical Trials Network

PubMed Central

Lindblad, Robert; Hu, Lian; Oden, Neal; Wakim, Paul; Rosa, Carmen; VanVeldhuisen, Paul

2016-01-01

Background Most substance use disorders (SUD) treatment clinical trials are too short and small to reliably estimate the incidence of rare events like death. Objective The aim of this study is to estimate the overall mortality rates among a SUD treatment-seeking population by pooling participants from multiple clinical trials conducted through the National Institute on Drug Abuse (NIDA)-sponsored National Drug Abuse Treatment Clinical Trials Network (CTN). Participants Drug and or alcohol users (N=9,866) who sought treatment and participated in one of the twenty-two CTN trials. Measurements Data were collected through randomized clinical trials in national community treatment programs (CTPs) for SUD. Pooled analysis was performed to assess age- and gender-standardized mortality rate(s) (SM rate(s)), and mortality ratio(s) (SM ratio(s)) of CTN trial participants compared to the U.S. general population. We also assessed if there were differences in mortality rates across different types of substance of abuse. Results The age- and gender-SM rate among CTN trials participants was 1403 (95% CI: 862-2074) per 100,000 person years (PY) compared to 542 (95% CI: 541-543) per 100,000 PY among the U.S. general population in 2005. By gender, age-adjusted SM ratio for female CTN trial participants was over five times (SM ratio=5.35, 95% CI: 3.31-8.19)), and for male CTN trial participants was over three times (SM ratio=3.39, 95% CI: 2.25-4.90) higher than their gender comparable peers in the U.S. general population. Conclusions Age and gender-standardized mortality rates and ratios among NIDA CTN SUD treatment-seeking clinical trial participants are higher than the age and gender comparable U.S. general population. The overall mortality rates of CTN trial participants are similar to in-treatment mortality reported in large U.S. and non-U.S. cohorts of opioid users. Future analysis with additional CTN trial participants and risk times will improve the stability of estimates

Comparative costs and activity from a sample of UK clinical trials units.

PubMed

Hind, Daniel; Reeves, Barnaby C; Bathers, Sarah; Bray, Christopher; Corkhill, Andrea; Hayward, Christopher; Harper, Lynda; Napp, Vicky; Norrie, John; Speed, Chris; Tremain, Liz; Keat, Nicola; Bradburn, Mike

2017-05-02

The costs of medical research are a concern. Clinical Trials Units (CTUs) need to better understand variations in the costs of their activities. Representatives of ten CTUs and two grant-awarding bodies pooled their experiences in discussions over 1.5 years. Five of the CTUs provided estimates of, and written justification for, costs associated with CTU activities required to implement an identical protocol. The protocol described a 5.5-year, nonpharmacological randomized controlled trial (RCT) conducted at 20 centres. Direct and indirect costs, the number of full time equivalents (FTEs) and the FTEs attracting overheads were compared and qualitative methods (unstructured interviews and thematic analysis) were used to interpret the results. Four members of the group (funding-body representatives or award panel members) reviewed the justification statements for transparency and information content. Separately, 163 activities common to trials were assigned to roles used by nine CTUs; the consistency of role delineation was assessed by Cohen's κ. Median full economic cost of CTU activities was £769,637 (range: £661,112 to £1,383,323). Indirect costs varied considerably, accounting for between 15% and 59% (median 35%) of the full economic cost of the grant. Excluding one CTU, which used external statisticians, the total number of FTEs ranged from 2.0 to 3.0; total FTEs attracting overheads ranged from 0.3 to 2.0. Variation in directly incurred staff costs depended on whether CTUs: supported particular roles from core funding rather than grants; opted not to cost certain activities into the grant; assigned clerical or data management tasks to research or administrative staff; employed extensive on-site monitoring strategies (also the main source of variation in non-staff costs). Funders preferred written justifications of costs that described both FTEs and indicative tasks for funded roles, with itemised non-staff costs. Consistency in role delineation was fair (κ�

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.

The Cooperative Landscape of Multinational Clinical Trials

PubMed Central

Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

2015-01-01

The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155

Transparency in ovarian cancer clinical trial results: ClinicalTrials.gov versus PubMed, Embase and Google scholar.

PubMed

Roberto, Anna; Radrezza, Silvia; Mosconi, Paola

2018-04-10

In recent years the question of the lack of transparency in clinical research has been debated by clinicians, researchers, citizens and their representatives, authors and publishers. This is particularly important for infrequent cancers such as ovarian cancer, where treatment still gives disappointing results in the majority of cases. Our aim was to assess the availability to the public of results in ClinicalTrials.gov, and the frequency of non-publication of results in ClinicalTrials.gov and in PubMed, Embase and Google Scholar. We collected all trials on ovarian cancer identified as "completed status" in the ClinicalTrials.gov registry on 17 January 2017. We checked the availability of the results in ClinicalTrials.gov and systematically identified published manuscripts on results. Out of 2725 trials on ovarian cancer identified, 752 were classified as "completed status". In those closed between 2008 and 2015, excluding phase I, the frequency of results in ClinicalTrials.gov was 35%. Of the 752 completed studies the frequency of published results in PubMed, Embase or Google Scholar ranged from 57.9% to 69.7% in the last years. These findings show a lack of transparency and credibility of research. Citizens or patients' representatives, with the medical community, should continuously support initiatives to improve the publication and dissemination of clinical study results.

Improving physical activity in arthritis clinical trial (IMPAACT): study design, rationale, recruitment, and baseline data.

PubMed

Chang, Rowland W; Semanik, Pamela A; Lee, Jungwha; Feinglass, Joseph; Ehrlich-Jones, Linda; Dunlop, Dorothy D

2014-11-01

Over 21 million Americans report an arthritis-attributable activity limitation. Knee osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common/disabling forms of arthritis. Various forms of physical activity (PA) can improve a variety of health outcomes and reduce health care costs, but the proportion of the US population engaging in the recommended amount of PA is low and even lower among those with arthritis. The Improving Motivation for Physical Activity in Arthritis Clinical Trial (IMPAACT) is a randomized clinical trial that studied the effects of a lifestyle PA promotion intervention on pain and physical function outcomes. The IMPAACT intervention was based on a chronic care/disease management model in which allied health professionals promote patient self-management activities outside of traditional physician office encounters. The program was a motivational interviewing-based, individualized counseling and referral intervention, directed by a comprehensive assessment of individual patient barriers and strengths related to PA performance. The specific aims of IMPAACT were to test the efficacy of the IMPAACT intervention for persons with arthritis (N=185 persons with RA and 155 persons with knee OA) in improving arthritis-specific and generic self-reported pain and Physical Function outcomes, observed measures of function, and objectively measured and self-reported PA levels. Details of the stratified-randomized study design, subject recruitment, and data collection are described. The results from IMPAACT will generate empiric evidence pertaining to increasing PA levels in persons with arthritis and result in widely applicable strategies for health behavior change. Copyright © 2014 Elsevier Inc. All rights reserved.

Emerging innovations in clinical trial design.

PubMed

Berry, D A

2016-01-01

Designs of clinical trials have changed little since the advent of randomization in the 1940s. Modern innovations in designs are being driven by the increasing recognition in clinical research that diseases are heterogeneous and patients who apparently have the same disease require different therapies. This article describes some innovations in clinical trial design across therapeutic areas but with a focus on oncology. No one knows what the future holds for clinical trial design but the status quo of large trials that pretend the patient population is homogeneous is not sustainable, either economically or scientifically/medically. No one knows what the eventual business model and regulatory model will be, but they will be very different from today's. © 2015 American Society for Clinical Pharmacology and Therapeutics.

NRG Oncology medical physicists' manpower survey quantifying support demands for multi-institutional clinical trials.

PubMed

Monroe, James I; Boparai, Karan; Xiao, Ying; Followill, David; Galvin, James M; Klein, Eric E; Low, Daniel A; Moran, Jean M; Zhong, Haoyu; Sohn, Jason W

2018-02-04

A survey was created by NRG to assess a medical physicists' percent full time equivalent (FTE) contribution to multi-institutional clinical trials. A 2012 American Society for Radiation Oncology report, "Safety Is No Accident," quantified medical physics staffing contributions in FTE factors for clinical departments. No quantification of FTE effort associated with clinical trials was included. To address this lack of information, the NRG Medical Physics Subcommittee decided to obtain manpower data from the medical physics community to quantify the amount of time medical physicists spent supporting clinical trials. A survey, consisting of 16 questions, was designed to obtain information regarding physicists' time spent supporting clinical trials. The survey was distributed to medical physicists at 1996 radiation therapy institutions included on the membership rosters of the 5 National Clinical Trials Network clinical trial groups. Of the 451 institutions who responded, 50% (226) reported currently participating in radiation therapy trials. On average, the designated physicist at each institution spent 2.4 hours (standard deviation [SD], 5.5) per week supervising or interacting with clinical trial staff. On average, 1.2 hours (SD, 3.1), 1.8 hours (SD, 3.9), and 0.6 hours (SD, 1.1) per week were spent on trial patient simulations, treatment plan reviews, and maintaining a Digital Imaging and Communications in Medicine server, respectively. For all trial credentialing activities, physicists spent an average of 32 hours (SD, 57.2) yearly. Reading protocols and supporting dosimetrists, clinicians, and therapists took an average of 2.1 hours (SD, 3.4) per week. Physicists also attended clinical trial meetings, on average, 1.2 hours (SD, 1.9) per month. On average, physicist spent a nontrivial total of 9 hours per week (0.21 FTE) supporting an average of 10 active clinical trials. This time commitment indicates the complexity of radiation therapy clinical trials and should

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

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

Hyperbaric oxygen: B-level evidence in mild traumatic brain injury clinical trials.

PubMed

Figueroa, Xavier A; Wright, James K

2016-09-27

First, to demonstrate that B-level evidence exists for the use of hyperbaric oxygen therapy (HBOT) as an effective treatment in mild to moderate traumatic brain injury/persistent postconcussion syndrome (mTBI/PPCS). Second, to alert readers and researchers that currently used pressurized air controls (≥21% O2, >1.0 ATA) are therapeutically active and cannot be utilized as sham controls without further validation. Review of published, peer-reviewed articles of HBOT prospective and controlled clinical trials of mTBI/PPCS symptoms. Published results demonstrate that HBOT is effective in the treatment of mTBI/PPCS symptoms. Doses of oxygen that are applied at ≥21% O2 and at pressures of >1.0 ATA produce improvements from baseline measures. Some of the recently published clinical trials are mischaracterized as sham-controlled clinical trials (i.e., sham = 21% O2/1.2-1.3 ATA), but are best characterized as dose-varying (variation in oxygen concentration, pressure applied, or both) clinical trials. Hyperbaric oxygen and hyperbaric air have demonstrated therapeutic effects on mTBI/PPCS symptoms and can alleviate posttraumatic stress disorder symptoms secondary to a brain injury in 5 out of 5 peer-reviewed clinical trials. The current use of pressurized air (1.2-1.3 ATA) as a placebo or sham in clinical trials biases the results due to biological activity that favors healing. © 2016 American Academy of Neurology.

Type 1 Diabetes TrialNet--an international collaborative clinical trials network.

PubMed

Skyler, Jay S; Greenbaum, Carla J; Lachin, John M; Leschek, Ellen; Rafkin-Mervis, Lisa; Savage, Peter; Spain, Lisa

2008-12-01

Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of type 1 diabetes (T1D). The fundamental goal of TrialNet is to counter the T1D disease process by immune modulation and/or enhancement of beta cell proliferation and regeneration. To achieve this goal, TrialNet researchers are working to better understand the natural history of the disease, to identify persons at risk, and to clinically evaluate novel therapies that balance potential risks and benefits. The particular focus is on studies of preventive measures. In addition, TrialNet evaluates therapies in individuals with newly diagnosed T1D with preserved beta cell function to help determine the risk/benefit profile and gain an initial assessment of potential efficacy in preservation of beta cell function, so that promising agents can be studied in prevention trials. In addition, TrialNet evaluates methodologies that enhance the conduct of its clinical trials, which includes tests of outcome assessment methodology, the evaluation of surrogate markers, and mechanistic studies laying the foundation for future clinical trials.

A web-based clinical trial management system for a sham-controlled multicenter clinical trial in depression.

PubMed

Durkalski, Valerie; Wenle Zhao; Dillon, Catherine; Kim, Jaemyung

2010-04-01

Clinical trial investigators and sponsors invest vast amounts of resources and energy into conducting trials and often face daily challenges with data management, project management, and data quality control. Rather than waiting months for study progress reports, investigators need the ability to use real-time data for the coordination and management of study activities across all study team members including site investigators, oversight committees, data and safety monitoring boards, and medical safety monitors. Web-based data management systems are beginning to meet this need but what distinguishes one system from the other are user needs/requirements and cost. To illustrate the development and implementation of a web-based data and project management system for a multicenter clinical trial designed to test the superiority of repeated transcranial magnetic stimulation versus sham for the treatment of patients with major depression. The authors discuss the reasons for not using a commercially available system for this study and describe the approach to developing their own web-based system for the OPT-TMS study. Timelines, effort, system architecture, and lessons learned are shared with the hope that this information will direct clinical trial researchers and software developers towards more efficient, user-friendly systems. The developers use a combination of generic and custom application code to allow for the flexibility to adapt the system to the needs of the study. Features of the system include: central participant registration and randomization; secure data entry at the site; participant progress/study calendar; safety data reporting; device accounting; monitor verification; and user-configurable generic reports and built-in customized reports. Hard coding was more time-efficient to address project-specific issues compared with the effort of creating a generic code application. As a consequence of this strategy, the required maintenance of the system is

Effect of European Clinical Trials Directive on academic drug trials in Denmark: retrospective study of applications to the Danish Medicines Agency 1993-2006.

PubMed

Berendt, Louise; Håkansson, Cecilia; Bach, Karin Friis; Dalhoff, Kim; Andreasen, Per Buch; Petersen, Lene Grejs; Andersen, Elin; Poulsen, Henrik Enghusen

2008-01-05

To determine the impact of the European Union's Clinical Trials Directive on the number of academic drug trials carried out in Denmark. Retrospective review of applications for drug trials to the Danish Medicines Agency, 1993-2006. Applications for drug trials for alternate years were classified as academic or commercial trials. A random subset of academic trials was reviewed for number of participants in and intended monitoring of the trials. Academic and commercial drug trials showed an identical steady decline from 1993 to 2006 and no noticeable change after 2004 when good clinical practice became mandatory for academic trials. The Clinical Trials Directive introduced in May 2004 to ensure good clinical practice for academic drug trials was not associated with a decline in research activity in Denmark; presumably because good clinical practice units had already been in place in Danish universities since 1999. With such an infrastructure academic researchers can do drug trials under the same regulations as drug companies.

Current status of registry of vaccine clinical trials conducted by Korean investigators in ClinicalTrials.gov, database of US National Institutes of Health.

PubMed

Cho, Jahyang; Kim, Bo Bae; Bae, Chong-Woo; Cha, Sung-Ho

2013-01-01

PubMed is not only includes international medical journals but also has a registration site for the ongoing clinical trials, such as ClinicalTrials.gov, under the supervision of US National Institutes of Health. We analyzed current status of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. As of October 2012, there are total of 72 trials found on registry of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. These trials were analyzed and classified by conditions of vaccine clinical trials, biologicals or drugs used in vaccine clinical trials, status of proceeding research, and list of sponsor and collaborators. Total 72 trials of vaccine clinical trials conducted by Korean investigators are classified by groups of infection (64 trials), cancer (4 trials), and others (4 trials). Infections group shown are as follows: poliomyelitis, pertussis, diphtheria, tetanus, and Haemophilus influenzae type b (10), influenza (9), human papillomavirus infection (8), pneumococcal vaccine (6), herpes zoster (4), smallpox (4), hepatitis B (4), etc. One trial of each in lung cancer, breast cancer, prostate cancer, and colorectal cancer are shown in cancer group. One trial of each in Crohn's disease, ulcerative colitis, renal failure, and rheumatoid arthritis are shown in other group. Vaccine clinical trials conducted by Korean investigators in ClinicalTrial.gov reflects the current status of Korean research on vaccine clinical trials at the international level and can indicate research progress. It is hoped that this aids the development of future vaccine clinical trials in Korea.

Importance of placebo effect in cough clinical trials.

PubMed

Eccles, Ron

2010-01-01

Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed.

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

Methodology Series Module 4: Clinical Trials.

PubMed

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.

Clinical Perspectives from Randomized Phase 3 Trials on Prostate Cancer: An Analysis of the ClinicalTrials.gov Database.

PubMed

Tsikkinis, Alexandros; Cihoric, Nikola; Giannarini, Gianluca; Hinz, Stefan; Briganti, Alberto; Wust, Peter; Ost, Piet; Ploussard, Guillaume; Massard, Christophe; Surcel, Cristian I; Sooriakumaran, Prasanna; Isbarn, Hendrik; De Visschere, Peter J L; Futterer, Jurgen J; van der Bergh, Roderick C N; Dal Pra, Alan; Aebersold, Daniel M; Budach, Volker; Ghadjar, Pirus

2015-09-01

It is not easy to overview pending phase 3 trials on prostate cancer (PCa), and awareness of these trials would benefit clinicians. To identify all phase 3 trials on PCa registered in the ClinicalTrials.gov database with pending results. On September 29, 2014, a database was established from the records for 175 538 clinical trials registered on ClinicalTrials.gov. A search of this database for the substring "prostat" identified 2951 prostate trials. Phase 3 trials accounted for 441 studies, of which 333 concerned only PCa. We selected only ongoing or completed trials with pending results, that is, for which the primary endpoint had not been published in a peer-reviewed medical journal. We identified 123 phase 3 trials with pending results. Trials were conducted predominantly in North America (n=63; 51%) and Europe (n=47; 38%). The majority were on nonmetastatic disease (n=82; 67%), with 37 (30%) on metastatic disease and four trials (3%) including both. In terms of intervention, systemic treatment was most commonly tested (n=71; 58%), followed by local treatment 34 (28%), and both systemic and local treatment (n=11; 9%), with seven (6%) trials not classifiable. The 71 trials on systemic treatment included androgen deprivation therapy (n=34; 48%), chemotherapy (n=15; 21%), immunotherapy (n=9; 13%), other systemic drugs (n=9; 13%), radiopharmaceuticals (n=2; 3%), and combinations (n=2; 3%). Local treatments tested included radiation therapy (n=27; 79%), surgery (n=5; 15%), and both (n=2; 2%). A limitation is that not every clinical trial is registered on ClinicalTrials.gov. There are many PCa phase 3 trials with pending results, most of which address questions regarding systemic treatments for both nonmetastatic and metastatic disease. Radiation therapy and androgen deprivation therapy are the interventions most commonly tested for local and systemic treatment, respectively. This report describes all phase 3 trials on prostate cancer registered in the ClinicalTrials

[Clinical trials registry].

PubMed

Ryder, Elena

2004-12-01

Authors and journals are more enthusiastic about the publication of trials with positive results than those negative or inconclusive trials. The International Committee of Medical Journal Editors proposed comprehensive trials registration as a solution to the problem of selective awareness and announces that the ICMJE member journals will adopt a trial-registration policy to promote this goal. They establish as a condition of consideration for publication, registration in a public trials registry. They recommend registries that meet certain criteria as www.clinicaltrials.com. Among those criteria is that the registry must be supported by a non-profit organization. On the other hand, people from Current Controlled Trials Ltd. being a commercial company, but meeting all the other criteria established by the ICMJE, feel that is being put aside. We wonder if clinical trials in our country are being registered in some of these International Registries. If not, would it be time to do so?

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.

Best clinical trials reported in 2010.

PubMed

Garner, John B; Grayburn, Paul A; Yancy, Clyde W

2011-07-01

Each year, a number of clinical trials emerge with data sufficient to change clinical practice. Determining which findings will result in practice change and which will provide only incremental benefit can be a dilemma for clinicians. The authors review selected clinical trials reported in 2010 in journals, at society meetings, and at conferences, focusing on those studies that have the potential to change clinical practice. This review offers 3 separate means of analysis: an abbreviated text summary, organized by subject area; a comprehensive table of relevant clinical trials that provides a schematic review of the hypotheses, interventions, methods, primary end points, results, and implications; and a complete bibliography for further reading as warranted. It is hoped that this compilation of relevant clinical trials and their important findings released in 2010 will be of benefit in the everyday practice of cardiovascular medicine. Copyright © 2011 Elsevier Inc. All rights reserved.

Increasing Recreational Physical Activity in Patients With Chronic Low Back Pain: A Pragmatic Controlled Clinical Trial.

PubMed

Ben-Ami, Noa; Chodick, Gabriel; Mirovsky, Yigal; Pincus, Tamar; Shapiro, Yair

2017-02-01

Study Design Prospective, pragmatic, nonrandomized controlled clinical trial. Background Clinical guidelines recommend physical activity for the treatment of chronic low back pain. But engaging patients in physical activity has proven difficult. Known obstacles to physical activity include low self-efficacy and fear avoidance. Objectives This study tested the effectiveness of an enhanced transtheoretical model intervention (ETMI) aimed at increasing recreational physical activity in patients with chronic low back pain, in comparison to usual physical therapy. Methods Patients (n = 220) referred to physical therapy for chronic low back pain were allocated to ETMI or to a control group. The ETMI was delivered by physical therapists and based on behavior-change principles, combined with increased reassurance, therapeutic alliance, and exposure to reduce fear avoidance. The primary outcome was back pain-related disability (Roland-Morris Disability Questionnaire). Secondary outcomes included pain intensity, mental and physical health, and levels of physical activity. Results Intention-to-treat analysis in 189 patients at 12 months indicated that patients in the ETMI group had significantly lower disability compared to usual physical therapy. The difference in mean change from baseline between the interventions was 2.7 points (95% confidence interval: 0.9, 4.5) on the Roland-Morris Disability Questionnaire. At 12 months, worst pain, physical activity, and physical health were all significantly better in patients receiving ETMI. The average number of sessions was 3.5 for the ETMI group and 5.1 for controls. Conclusion Targeting obstacles to physical activity with an intervention that includes components to address self-efficacy and fear avoidance appears to be more effective than usual physical therapy care in reducing long-term disability. Further research is needed to explore the mechanisms that impact outcomes in this intervention package. Level of Evidence Therapy

The mPED randomized controlled clinical trial: applying mobile persuasive technologies to increase physical activity in sedentary women protocol.

PubMed

Fukuoka, Yoshimi; Komatsu, Judith; Suarez, Larry; Vittinghoff, Eric; Haskell, William; Noorishad, Tina; Pham, Kristin

2011-12-14

Despite the significant health benefits of regular physical activity, approximately half of American adults, particularly women and minorities, do not meet the current physical activity recommendations. Mobile phone technologies are readily available, easily accessible and may provide a potentially powerful tool for delivering physical activity interventions. However, we need to understand how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women. The purpose of this paper is to describe the study design and protocol of the mPED (mobile phone based physical activity education) randomized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions. A randomized controlled trial (RCT) with three arms; 1) PLUS (3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention), 2) REGULAR (3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention), and 3) CONTROL (pedometer only, but no intervention will be conducted). A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be randomized into one of the three groups. The mobile phone serves as a means of delivering the physical activity intervention, setting individualized weekly physical activity goals, and providing self-monitoring (activity diary), immediate feedback and social support. The mobile phone also functions as a tool for communication and real-time data capture. The primary outcome is objectively measured physical activity. If efficacy of the intervention with a mobile phone is demonstrated, the results of this RCT will be able to provide new insights for current behavioral sciences and mHealth. ClinicalTrials.gov#:NCTO1280812.

EAP viewpoint on unpublished data from paediatric clinical trials.

PubMed

Schrier, L; Illy, K; Valiulis, A; Wyder, C; Stiris, T

2018-02-01

European children and paediatricians rely heavily on the fair, complete and timely publication of data obtained from paediatric randomised controlled trials (RCTs). Selective publication and reporting of paediatric RCTs is common practice. Industry-sponsored trials are more likely to remain unpublished, and take longer to get published compared with trials sponsored by others. However, also academic sponsors contribute to inefficiencies in publishing clinical data. Publication bias violates the ethical obligation that investigators have towards study participants, leads to considerable inefficiencies in research and a waste of financial and human resources, and has the potential to distort evidence for treatment approaches. The European Academy of Paediatrics (EAP) therefore actively supports initiatives that increase the public dissemination of paediatric clinical trial data. The EAP will raise awareness about the guidelines for Good Publication Practice among European paediatricians and subspecialty societies.

Inclusion of Minority Patients in Breast Cancer Clinical Trials: The Role of the Clinical Trial Environment

DTIC Science & Technology

2008-05-01

trials, site cultural competence, and outreach efforts. We will also examine the social and physical characteristics of the community surrounding the...clinical trial sites and those that address specific barriers associated with the social or physical environment. 2 Body This annual report...indicators. Data will be collected to characterize both the physical environment and the social environment surrounding clinical trials. The

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

[Features of Clinical Register of Chinese Medicine and Pharmacy Based on ClinicalTrials.gov. (USA)].

PubMed

Lu, Peng-fei; Liao, Xing; Xie, Yan-ming; Wang, Zhi-guo

2015-11-01

In recent 10 years, clinical trials of Chinese medicine and pharmacy (cMP) at clinicalTrials.gov.(USA) are gradually increasing. In order to analyze features of CMP clinical register, ClinicalTrials.gov register database were comprehensively retrieved in this study. Included clinical trials were input one item after another using EXCEL. A final of 348 CMP clinical trials were included. Results showed that China occupied the first place in CMP clinical register, followed by USA. CMP clinical trials, sponsored mainly by colleges/universities and hospitals, mostly covered interventional studies on evaluating safety/effectiveness of CMP. The proportions of studies, sponsored by mainland China and companies, recruitment trials and multi-center clinical trials in interventional trials were increasing. The proportions of studies sponsored by Hong Kong and Taiwan, research completed trials, unclear research status, phase III clinical trials, and published research trials in interventional trials were decreasing. Published ratios of CMP clinical trials were quite low. There were more missing types and higher proportions in trial register information.

Impact of the European Clinical Trials Directive on academic clinical research.

PubMed

Baeyens, A J

2004-01-01

With the adoption of the Clinical Trials Directive it was Europe's intention to make the performance of multi-national clinical trials in Europe easier through the harmonization of the regulatory procedures. As the Directive was mainly conceived to facilitate the performance of multi-national clinical trials to develop new drugs, it is to be determined to what extent academic clinical trials will be concerned by the Directive and more importantly what will be its impact on daily academic clinical research. Contrary to several national regulations the scope of the Directive is very large only excluding non-interventional trials. This implies that most of the academic clinical trials will be concerned by the Directive. Besides the handling of the regulatory procedures in the different countries, issues related to insurance, labeling requirements and provision of the investigational medical products will expose the academic sponsor to additional administrative and financial challenges that will have to be handled appropriately, as the academic sponsors will be controlled by Inspectors regarding their compliance with the new regulations to come.

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

Clinical trials attitudes and practices of Latino physicians.

PubMed

Ramirez, Amelie G; Wildes, Kimberly; Talavera, Greg; Nápoles-Springer, Anna; Gallion, Kipling; Pérez-Stable, Eliseo J

2008-07-01

Ethnic differences in physicians' attitudes and behaviors related to clinical trials might partially account for disparities in clinical trial participation among Latino patients. Literature regarding Latino physicians' clinical trials attitudes and practices, in comparison to White physicians, was lacking. Cross-sectional data from randomly selected physicians (N=695), stratified by ethnicity, were analyzed to test associations of ethnicity with physicians' participation in and attitudes toward referral of patients to clinical trials. Chi-square analyses showed significant (p<0.05) associations of physician race/ethnicity and clinical trials involvement, type of trial for which the physician is likely to recommend a patient, belief in scientific value, and factors that would influence recommendation for a patient to participate. Multivariate analyses resulted in several significant (p<0.05) predictors of clinical trials outcomes, including physician race/ethnicity. Latino physicians were significantly less involved in clinical trials than White physicians and found less scientific value in them, highlighting areas for future education and intervention.

[Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

PubMed

Shimada, Yasuhiro

2016-04-01

The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

Clinical relevance of findings in trials of CBT for depression.

PubMed

Lepping, P; Whittington, R; Sambhi, R S; Lane, S; Poole, R; Leucht, S; Cuijpers, P; McCabe, R; Waheed, W

2017-09-01

Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression - Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD. Copyright © 2017. Published by Elsevier Masson SAS.

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.

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

A data grid for imaging-based clinical trials

NASA Astrophysics Data System (ADS)

Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

2007-03-01

Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

Active implementation strategy of CONSORT adherence by a dental specialty journal improved randomized clinical trial reporting.

PubMed

Pandis, Nikolaos; Shamseer, Larissa; Kokich, Vincent G; Fleming, Padhraig S; Moher, David

2014-09-01

To describe a novel CONsolidated Standards of Reporting Trials (CONSORT) adherence strategy implemented by the American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO) and to report its impact on the completeness of reporting of published trials. The AJO-DO CONSORT adherence strategy, initiated in June 2011, involves active assessment of randomized clinical trial (RCT) reporting during the editorial process. The completeness of reporting CONSORT items was compared between trials submitted and published during the implementation period (July 2011 to September 2013) and trials published between August 2007 and July 2009. Of the 42 RCTs submitted (July 2011 to September 2013), 23 were considered for publication and assessed for completeness of reporting, seven of which were eventually published. For all published RCTs between 2007 and 2009 (n = 20), completeness of reporting by CONSORT item ranged from 0% to 100% (Median = 40%, interquartile range = 60%). All published trials in 2011-2013, reported 33 of 37 CONSORT (sub) items. Four CONSORT 2010 checklist items remained problematic even after implementation of the adherence strategy: changes to methods (3b), changes to outcomes (6b) after the trial commenced, interim analysis (7b), and trial stopping (14b), which are typically only reported when applicable. Trials published following implementation of the AJO-DO CONSORT adherence strategy completely reported more CONSORT items than those published or submitted previously. Copyright © 2014 Elsevier Inc. All rights reserved.

Recommendations for imaging tumor response in neurofibromatosis clinical trials

PubMed Central

Ardern-Holmes, Simone L.; Babovic-Vuksanovic, Dusica; Barker, Fred G.; Connor, Steve; Evans, D. Gareth; Fisher, Michael J.; Goutagny, Stephane; Harris, Gordon J.; Jaramillo, Diego; Karajannis, Matthias A.; Korf, Bruce R.; Mautner, Victor; Plotkin, Scott R.; Poussaint, Tina Y.; Robertson, Kent; Shih, Chie-Schin; Widemann, Brigitte C.

2013-01-01

Objective: Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Methods: Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. Results: MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. Conclusions: The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors. PMID:24249804

Recommendations for imaging tumor response in neurofibromatosis clinical trials.

PubMed

Dombi, Eva; Ardern-Holmes, Simone L; Babovic-Vuksanovic, Dusica; Barker, Fred G; Connor, Steve; Evans, D Gareth; Fisher, Michael J; Goutagny, Stephane; Harris, Gordon J; Jaramillo, Diego; Karajannis, Matthias A; Korf, Bruce R; Mautner, Victor; Plotkin, Scott R; Poussaint, Tina Y; Robertson, Kent; Shih, Chie-Schin; Widemann, Brigitte C

2013-11-19

Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors.

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

Qualitative analysis of clinical research coordinators' role in phase I cancer clinical trials.

PubMed

Fujiwara, Noriko; Ochiai, Ryota; Shirai, Yuki; Saito, Yuko; Nagamura, Fumitaka; Iwase, Satoru; Kazuma, Keiko

2017-12-01

Clinical research coordinators play a pivotal role in phase I cancer clinical trials. We clarified the care coordination and practice for patients provided by clinical research coordinators in phase I cancer clinical trials in Japan and elucidated clinical research coordinators' perspective on patients' expectations and understanding of these trials. Fifteen clinical research coordinators participated in semi-structured interviews regarding clinical practices; perceptions of patients' expectations; and the challenges that occur before, during, and after phase I cancer clinical trials. Qualitative content analysis showed that most clinical research coordinators observed that patients have high expectations from the trials. Most listened to patients to confirm patients' understanding and reflected on responses to maintain hope, but to avoid excessive expectations; clinical research coordinators considered avoiding unplanned endings; and they aimed to establish good relationships between patients, medical staff, and among the professional team. Clinical research coordinators were insightful about the needs of patients and took a meticulous approach to the phase I cancer clinical trial process, allowing time to connect with patients and to coordinate the inter-professional research team. Additionally, education in advanced oncology care was valuable for comforting participants in cancer clinical trials.

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

2017-12-01

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.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

PubMed Central

May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

2011-01-01

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30–40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

Impact of the European clinical trials directive on prospective academic clinical trials associated with BMT.

PubMed

Frewer, L J; Coles, D; van der Lans, I A; Schroeder, D; Champion, K; Apperley, J F

2011-03-01

The European Clinical Trials Directive (EU 2001; 2001/20/EC) was introduced to improve the efficiency of commercial and academic clinical trials. Concerns have been raised by interested organizations and institutions regarding the potential for negative impact of the Directive on non-commercial European clinical research. Interested researchers within the European Group for Blood and Marrow Transplantation (EBMT) were surveyed to determine whether researcher experiences confirmed this view. Following a pilot study, an internet-based questionnaire was distributed to individuals in key research positions in the European haemopoietic SCT community. Seventy-one usable questionnaires were returned from participants in different EU member states. The results indicate that the perceived impact of the European Clinical Trials Directive has been negative, at least in the research areas of interest to the EBMT.

Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative.

PubMed

Greenberg, Rachel G; Corneli, Amy; Bradley, John; Farley, John; Jafri, Hasan S; Lin, Li; Nambiar, Sumathi; Noel, Gary J; Wheeler, Chris; Tiernan, Rosemary; Smith, P Brian; Roberts, Jamie; Benjamin, Daniel K

2018-03-01

Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator (those who have never served as a clinical trial investigator) providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. We conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials. Using a 4-point Likert scale, providers described their perception of potential barriers to their practice serving as a site for pediatric clinical trials. Of the 136 providers surveyed, 52/136 (38%) had previously referred a pediatric patient to a trial, and only 17/136 (12%) had ever been an investigator for a pediatric trial. Lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. Overall, providers perceived greater challenges related to parental concerns and parent or child logistical barriers than study implementation and ethics or regulatory barriers as barriers to their practice serving as a trial site. Providers who had previously been an investigator for a pediatric trial were less likely to be concerned with potential barriers than non-investigators. Understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation.

Design Dilemma: The Debate over Using Placebos in Cancer Clinical Trials

Cancer.gov

Many patients and researchers assert that in cancer clinical trials, placebos are inappropriate and that all participants should receive active treatment. But with the emergence of molecularly targeted anticancer agents, some cancer researchers believe placebo-controlled trials are now feasible and, in some cases, necessary.

Global women's health: current clinical trials in low- and middle-income countries.

PubMed

Merriel, A; Harb, H M; Williams, H; Lilford, R; Coomarasamy, A

2015-01-01

Clinical trials in low- and middle-income countries (LMICs) are necessary to develop evidence-based approaches to improve women's health. Understanding what research is currently being conducted will allow the identification of research gaps, avoidance of duplication, planning of future studies, collaboration amongst research groups, and geographical targeting for research investments. To provide an overview of active women's health trials in LMICs. The World Health Organization's International Clinical Trials Registry Platform was searched for trials registered between 1 April 2012 and 31 March 2014. Selected trials were randomised, conducted in LMICs, active, and with a women's health intervention or a significant outcome for the woman. Two reviewers extracted data. Analysis included geographical spread, speciality areas, pre-enrolment registration, study size, and funders. Of the 8966 records, 509 were eligible for inclusion. Gynaecology trials made up 57% of the research, whereas the remaining 43% of trials were in obstetrics. Research activity focused on fertility (17%), the antenatal period (15%), benign gynaecology (14%), intrapartum care (9%), and pre-invasive disease and cancers (8%). The majority of trials (84%) took place in middle-income countries (MICs). In low-income countries (LICs) 83% of research investigated obstetrics, and in MICs 60% of research investigated gynaecology. Most trials (80%) had a sample size of 500 or fewer participants. The median size of trials in LICs was 815 compared with 128 in MICs. Pre-enrolment registration occurred in 54% of trials. The majority (62%) of trials were funded locally. Many LMICs are active in women's health research. The majority of registered trials are located in MICs; however, the trials in LICs are often larger. The focus of research in MICs may be driven by local priorities and funding, with fertility being highly researched. In LICs, pregnancy is the focus, perhaps reflecting the international

A commentary on transdermal drug delivery systems in clinical trials.

PubMed

Watkinson, Adam C

2013-09-01

The number of drugs available as marketed transdermal products is limited to those that exhibit the correct physicochemical and pharmacokinetic properties that enable their effective delivery across the skin. In this respect, there are less than 20 drugs that are currently marketed in the US and EU as products that deliver systemic levels of their active ingredients. An analysis of clinical trials conducted in the transdermal sector shows a similar picture with only nine drugs accounting for approximately 80% of all transdermal clinical trials listed on ClinicalTrials.gov. Those drugs for which there are very few transdermal trials listed consist mostly of molecules that are inherently unsuitable for transdermal delivery and serve as a clear warning to drug developers that the science that governs transdermal drug delivery is well reflected by the successes and failures of drugs in development as well as those that make it to the market. Copyright © 2013 Wiley Periodicals, Inc.

Assessing the challenges of multi-scope clinical research sites: an example from NIH HIV/AIDS clinical trials networks.

PubMed

Rosas, Scott R; Cope, Marie T; Villa, Christie; Motevalli, Mahnaz; Utech, Jill; Schouten, Jeffrey T

2014-04-01

Large-scale, multi-network clinical trials are seen as a means for efficient and effective utilization of resources with greater responsiveness to new discoveries. Formal structures instituted within the National Institutes of Health (NIH) HIV/AIDS Clinical Trials facilitate collaboration and coordination across networks and emphasize an integrated approach to HIV/AIDS vaccine, prevention and therapeutics clinical trials. This study examines the joint usage of clinical research sites as means of gaining efficiency, extending capacity, and adding scientific value to the networks. A semi-structured questionnaire covering eight clinical management domains was administered to 74 (62% of sites) clinical site coordinators at single- and multi-network sites to identify challenges and efficiencies related to clinical trials management activities and coordination with multi-network units. Overall, respondents at multi-network sites did not report more challenges than single-network sites, but did report unique challenges to overcome including in the areas of study prioritization, community engagement, staff education and training, and policies and procedures. The majority of multi-network sites reported that such affiliations do allow for the consolidation and cost-sharing of research functions. Suggestions for increasing the efficiency or performance of multi-network sites included streamlining standards and requirements, consolidating protocol activation methods, using a single cross-network coordinating centre, and creating common budget and payment mechanisms. The results of this assessment provide important information to consider in the design and management of multi-network configurations for the NIH HIV/AIDS Clinical Trials Networks, as well as others contemplating and promoting the concept of multi-network settings. © 2013 John Wiley & Sons Ltd.

Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases.

PubMed

Artusi, Carlo Alberto; Mishra, Murli; Latimer, Patricia; Vizcarra, Joaquin A; Lopiano, Leonardo; Maetzler, Walter; Merola, Aristide; Espay, Alberto J

2018-01-01

We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders. We systematically reviewed PubMed and ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints. We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials. Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

NCI National Clinical Trials Network Structure

Cancer.gov

Learn about how the National Clinical Trials Network (NCTN) is structured. The NCTN is a program of the National Cancer Institute that gives funds and other support to cancer research organizations to conduct cancer clinical trials.

Recent clinical trials in valvular heart disease.

PubMed

Kiss, Daniel; Anwaruddin, Saif

2017-07-01

With widespread adoption of transcatheter aortic valve replacement, there has been a change in the approach to management of valvular heart disease. New interest has taken hold in transcatheter therapies for valvular heart disease, as well as research into pathophysiology and progression of disease. Additionally, several key trials have further refined our understanding of surgical management of valvular heart disease. This review will elucidate recent clinical trial data leading to changes in practice. There have been several landmark trials expanding the indications for transcatheter aortic valve replacement. Additionally, although still early, trials are beginning to demonstrate the feasibility and safety of transcatheter mitral valves. Options for transcatheter management of right-sided valvular disease continue to evolve, and these are areas of active investigation. The emergence of novel therapies for valvular heart disease has expanded the management options available, allowing physicians to better individualize treatment of patients with valvular heart disease. This review will focus on the recent (within 2 years) trials in this field of interest.

Clinical Research and Clinical Trials

MedlinePlus

... NICHD News Videos OUTREACH Safe to Sleep® National Child & Maternal Health Education Program RELATED WEBSITES NIH.gov HHS.gov USA.gov ClinicalTrials.gov WEBSITE POLICIES Disclaimer FOIA Privacy Policy Accessibility NIH...Turning Discovery Into Health ®

Impact of Prior Cancer on Eligibility for Lung Cancer Clinical Trials

PubMed Central

Laccetti, Andrew L.; Xuan, Lei; Halm, Ethan A.; Pruitt, Sandi L.

2014-01-01

Background In oncology clinical trials, the assumption that a prior cancer diagnosis could interfere with study conduct or outcomes results in frequent exclusion of such patients. We determined the prevalence and characteristics of this practice in lung cancer clinical trials and estimated impact on trial accrual. Methods We reviewed lung cancer clinical trials sponsored or endorsed by the Eastern Oncology Cooperative Group for exclusion criteria related to a prior cancer diagnosis. We estimated prevalence of prior primary cancer diagnoses among lung cancer patients using Surveillance Epidemiology and End Results (SEER)-Medicare linked data. We assessed the association between trial characteristics and prior cancer exclusion using chi-square analysis. All statistical tests were two-sided. Results Fifty-one clinical trials (target enrollment 13072 patients) were included. Forty-one (80%) excluded patients with a prior cancer diagnosis as follows: any prior (14%), within five years (43%), within two or three years (7%), or active cancer (16%). In SEER-Medicare data (n = 210509), 56% of prior cancers were diagnosed within five years before the lung cancer diagnosis. Across trials, the estimated number and proportion of patients excluded because of prior cancer ranged from 0–207 and 0%-18%. Prior cancer was excluded in 94% of trials with survival primary endpoints and 73% of trials with nonsurvival primary endpoints (P = .06). Conclusions A substantial proportion of patients are reflexively excluded from lung cancer clinical trials because of prior cancer. This inclusion criterion is applied widely across studies, including more than two-thirds of trials with nonsurvival endpoints. More research is needed to understand the basis and ramifications of this exclusion policy. PMID:25253615

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

PubMed

Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

2016-11-23

Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Visual scoring of non-cavitated caries lesions and clinical trial efficiency, testing xylitol in caries active adults

PubMed Central

Brown, JP; Amaechi, BT; Bader, JD; Gilbert, GH; Makhija, SK; Lozano-Pineda, J; Leo, MC; Chuhe, C; Vollmer, WM

2013-01-01

Objectives To better understand the effectiveness of xylitol in caries prevention in adults, and to attempt improved clinical trial efficiency. Methods As part of the Xylitol for Adult Caries Trial (X-ACT), non-cavitated and cavitated caries lesions were assessed in subjects who were experiencing the disease. The trial was a test of the effectiveness of 5 grams/day of xylitol, consumed by dissolving in the mouth five 1 gram lozenges spaced across each day, compared with a sucralose placebo. For this analysis, seeking trial efficiency, 538 subjects aged 21–80, with complete data for four dental examinations were selected from the 691 randomized into the three year trial, conducted at three sites. Acceptable inter and intra examiner reliability before and during the trial was quantified using the kappa statistic. Results The mean annualized non-cavitated plus cavitated lesion transition scores in coronal and root surfaces, from sound to carious favoured xylitol over placebo, during the three cumulative periods of 12, 24, and 33 months, but these clinically and statistically non-significant differences declined in magnitude over time. Restricting the present assessment to those subjects with a higher baseline lifetime caries experience showed possible but inconsistent benefit. Conclusions There was no clear and clinically relevant preventive effect of xylitol on caries in adults with adequate fluoride exposure when non-cavitated plus cavitated lesions were assessed. This conformed to the X-ACT trial result assessing cavitated lesions. Including non-cavitated lesion assessment in this full scale, placebo controlled, multi site, randomized, double blinded clinical trial in adults experiencing dental caries, did not achieve added trial efficiency or demonstrate practical benefit of xylitol. Trial Registration ClinicalTrials.Gov NCT00393055 PMID:24205951

Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design.

PubMed

Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

2016-12-01

This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical

Design of control-group conditions in clinical trials of behavioral interventions.

PubMed

Lindquist, Ruth; Wyman, Jean F; Talley, Kristine M C; Findorff, Mary J; Gross, Cynthia R

2007-01-01

To review considerations in the design of placebo (attention) control conditions for community-based clinical trials of health behavior change interventions and to provide practical strategies for the design of control conditions. A well-designed control condition is an essential component of a clinical trial to foster the unambiguous interpretation of study findings. Pitfalls in the design of control conditions in clinical trials of behavioral interventions are identified and strategies to address them are offered. Types of control conditions that have been used in fall prevention trials are described, along with their strengths and weaknesses. The control condition used in the recent fall evaluation and prevention program (FEPP) was designed to overcome limitations of previous trial designs; it is provided to illustrate how to apply specific design principles. Pitfalls in the design of behavioral intervention studies may be avoided with the application of sound design principles. The FEPP active control condition can be used as a model in the design of future studies.

Facilitating large-scale clinical trials: in Asia.

PubMed

Choi, Han Yong; Ko, Jae-Wook

2010-01-01

The number of clinical trials conducted in Asian countries has started to increase as a result of expansion of the pharmaceutical market in this area. There is a growing opportunity for large-scale clinical trials because of the large number of patients, significant market potential, good quality of data, and the cost effective and qualified medical infrastructure. However, for carrying out large-scale clinical trials in Asia, there are several major challenges, including the quality control of data, budget control, laboratory validation, monitoring capacity, authorship, staff training, and nonstandard treatment that need to be considered. There are also several difficulties in collaborating on international trials in Asia because Asia is an extremely diverse continent. The major challenges are language differences, diversity of patterns of disease, and current treatments, a large gap in the experience with performing multinational trials, and regulatory differences among the Asian countries. In addition, there are also differences in the understanding of global clinical trials, medical facilities, indemnity assurance, and culture, including food and religion. To make regional and local data provide evidence for efficacy through the standardization of these differences, unlimited effort is required. At this time, there are no large clinical trials led by urologists in Asia, but it is anticipated that the role of urologists in clinical trials will continue to increase. Copyright © 2010 Elsevier Inc. All rights reserved.

SU-F-T-237: The Imaging and Radiation Oncology Core (IROC) Cooperatives Activities Supporting the NCI’s National Clinical Trial Network

DOE Office of Scientific and Technical Information (OSTI.GOV)

Followill, D; Galvin, J; Michalski, J

Purpose: The Imaging and Radiation Oncology Core (IROC) Cooperative has been active for the past two years supporting the National Clinical Trial Network and the details of that support are reported. Methods: There are six QA centers (Houston, Ohio, Philadelphia-RT, Philadelphia-DI, Rhode Island, St. Louis) providing an integrated RT and DI quality control program in support of the NCI’s clinical trials. The QA Center’s efforts are focused on assuring high quality data for clinical trials designed to improve the clinical outcomes for cancer patients worldwide. This program is administered through five core services: site qualification, trial design support, credentialing, datamore » management, and case review. Results: IROC currently provides core support for 172 NCTN trials with RT, DI and RT/DI components. Many of these trials were legacy trial from the previous cooperative group program. IROC monitors nearly 1800 RT photon and 20 proton institutions. Over 28,000 beams outputs were monitored with 8% of the sites requiring repeat audits due to beam out of criteria. As part of credentialing, 950 QA phantoms have been irradiated, 515 imaging modalities evaluated and almost 4000 credentialing letters have been issued. In just year 2, 5290 RT and 4934 DI patient datasets were received (many using TRIAD) by IROC QA Centers to be prepared for review. During the past 2 years, a total of 6300 RT cases and 19,000 DI image sets were reviewed by IROC technical staff. To date, IROC has published 36 manuscripts. Conclusion: The QA services provided by IROC are numerous and are continually being evaluated for effectiveness, harmonized across all NCTN Groups and administered in an efficient and timely manner to enhance accurate and per protocol trial data submission. These efforts increase each NCTN Group’s ability to derive meaningful outcomes from their clinical trials. This work was supported by DHHS NIH grant 5U24CA180803.« less

What Are Clinical Trials? | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn Javascript on. Feature: Clinical Trials What Are Clinical Trials? Past Issues / Fall 2010 Table of Contents ... conducted all the time. The Different Phases of Clinical Trials Clinical trials related to drugs are classified ...

Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool.

PubMed

Good, Marjorie J; Hurley, Patricia; Woo, Kaitlin M; Szczepanek, Connie; Stewart, Teresa; Robert, Nicholas; Lyss, Alan; Gönen, Mithat; Lilenbaum, Rogerio

2016-05-01

Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings. Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters. Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others. The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings. Copyright © 2016 by American Society of Clinical Oncology.

Compliance with results reporting at ClinicalTrials.gov.

PubMed

Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert M

2015-03-12

The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic

Engaging diverse communities participating in clinical trials: case examples from across Africa.

PubMed

Nyika, Aceme; Chilengi, Roma; Ishengoma, Deus; Mtenga, Sally; Thera, Mahamadou A; Sissoko, Mahamadou S; Lusingu, John; Tiono, Alfred B; Doumbo, Ogobara; Sirima, Sodiomon B; Lemnge, Martha; Kilama, Wen L

2010-03-26

In the advent of increasing international collaborative research involving participants drawn from populations with diverse cultural backgrounds, community engagement becomes very critical for the smooth conduction of the research. The African Malaria Network Trust (AMANET) is a pan-African non-governmental organization that sponsors and technically supports malaria vaccine trials in various African countries. AMANET sponsored phase Ib or IIb clinical trials of several malaria vaccine candidates in various Africa countries. In Burkina Faso, Mali and Tanzania trials of the merozoite surface protein 3 -- in its Long Synthetic Peptide configuration (MSP3 LSP) -- were conducted. In Mali, the apical membrane antigen 1 (AMA1) was tested, while a hybrid of glutamate rich protein (GLURP) and MSP3 (GMZ2) was tested in Gabon. AMANET recognizes the importance of engaging with the communities from which trial participants are drawn, hence community engagement was given priority in all project activities conducted in the various countries. Existing local social systems were used to engage the communities from which clinical trial participants were drawn. This article focuses on community engagement activities employed at various AMANET-supported clinical trial sites in different countries, highlighting subtle differences in the approaches used. The paper also gives some general pros and cons of community engagement. Community engagement enables two-way sharing of accurate information and ideas between researchers and researched communities, which helps to create an environment conducive to smooth research activities with enhanced sense of research ownership by the communities.

Patient choice in opt-in, active choice, and opt-out HIV screening: randomized clinical trial.

PubMed

Montoy, Juan Carlos C; Dow, William H; Kaplan, Beth C

2016-01-19

What is the effect of default test offers--opt-in, opt-out, and active choice--on the likelihood of acceptance of an HIV test among patients receiving care in an emergency department? This was a randomized clinical trial conducted in the emergency department of an urban teaching hospital and regional trauma center. Patients aged 13-64 years were randomized to opt-in, opt-out, and active choice HIV test offers. The primary outcome was HIV test acceptance percentage. The Denver Risk Score was used to categorize patients as being at low, intermediate, or high risk of HIV infection. 38.0% (611/1607) of patients in the opt-in testing group accepted an HIV test, compared with 51.3% (815/1628) in the active choice arm (difference 13.3%, 95% confidence interval 9.8% to 16.7%) and 65.9% (1031/1565) in the opt-out arm (difference 27.9%, 24.4% to 31.3%). Compared with active choice testing, opt-out testing led to a 14.6 (11.1 to 18.1) percentage point increase in test acceptance. Patients identified as being at intermediate and high risk were more likely to accept testing than were those at low risk in all arms (difference 6.4% (3.4% to 9.3%) for intermediate and 8.3% (3.3% to 13.4%) for high risk). The opt-out effect was significantly smaller among those reporting high risk behaviors, but the active choice effect did not significantly vary by level of reported risk behavior. Patients consented to inclusion in the study after being offered an HIV test, and inclusion varied slightly by treatment assignment. The study took place at a single county hospital in a city that is somewhat unique with respect to HIV testing; although the test acceptance percentages themselves might vary, a different pattern for opt-in versus active choice versus opt-out test schemes would not be expected. Active choice is a distinct test regimen, with test acceptance patterns that may best approximate patients' true preferences. Opt-out regimens can substantially increase HIV testing, and opt

Patient choice in opt-in, active choice, and opt-out HIV screening: randomized clinical trial

PubMed Central

Dow, William H; Kaplan, Beth C

2016-01-01

Study question What is the effect of default test offers—opt-in, opt-out, and active choice—on the likelihood of acceptance of an HIV test among patients receiving care in an emergency department? Methods This was a randomized clinical trial conducted in the emergency department of an urban teaching hospital and regional trauma center. Patients aged 13-64 years were randomized to opt-in, opt-out, and active choice HIV test offers. The primary outcome was HIV test acceptance percentage. The Denver Risk Score was used to categorize patients as being at low, intermediate, or high risk of HIV infection. Study answer and limitations 38.0% (611/1607) of patients in the opt-in testing group accepted an HIV test, compared with 51.3% (815/1628) in the active choice arm (difference 13.3%, 95% confidence interval 9.8% to 16.7%) and 65.9% (1031/1565) in the opt-out arm (difference 27.9%, 24.4% to 31.3%). Compared with active choice testing, opt-out testing led to a 14.6 (11.1 to 18.1) percentage point increase in test acceptance. Patients identified as being at intermediate and high risk were more likely to accept testing than were those at low risk in all arms (difference 6.4% (3.4% to 9.3%) for intermediate and 8.3% (3.3% to 13.4%) for high risk). The opt-out effect was significantly smaller among those reporting high risk behaviors, but the active choice effect did not significantly vary by level of reported risk behavior. Patients consented to inclusion in the study after being offered an HIV test, and inclusion varied slightly by treatment assignment. The study took place at a single county hospital in a city that is somewhat unique with respect to HIV testing; although the test acceptance percentages themselves might vary, a different pattern for opt-in versus active choice versus opt-out test schemes would not be expected. What this paper adds Active choice is a distinct test regimen, with test acceptance patterns that may best approximate patients’ true

How redesigning AD clinical trials might increase study partners' willingness to participate.

PubMed

Karlawish, Jason; Cary, Mark S; Rubright, Jonathan; Tenhave, Tom

2008-12-02

Timely recruiting and retaining participants into Alzheimer disease (AD) clinical trials is a challenge. We used conjoint analysis to identify how alterations in attributes of clinical trial design improve willingness to participate: risk, home visits, car service, or increased chance of receiving intervention. A total of 108 study partners of patients with very mild to severe stage AD rated willingness to allow their relative to participate in eight clinical trials that varied combinations of the four attributes. The highest utility was for home visits (0.89) which essentially compensated for the disutility of high risk (-0.85). The combination of home visits and car service was redundant, with almost no increase in utility over home visits alone. Seventeen percent were willing to participate in a trial with no amenities; the addition of home visits increased predicted willingness to participate to 27%; low risk, home visits, and higher chance of active treatment increased predicted willingness to 60%. The value of reducing the hassles of travel correlated well with measures of AD severity (activities of daily living r = 0.41, p < 0.001; basic activities of daily living r = 0.38, p < 0.001; Neuropsychiatric Inventory severity p = 0.24, p = 0.01; Neuropsychiatric Inventory distress r = 0.23, p < 0.02). No association was found between degree of study partner burden and willingness to tolerate risk of an intervention. Clinical trials that reduce travel inconvenience may offset the disincentive of study features such as the risk of intervention and may also increase willingness to participate. Redesigning trials may also help recruit patients with more severe Alzheimer disease. Shorter recruitment periods and increased retention rates may offset costs of these changes.

Regulating clinical trials in India: the economics of ethics.

PubMed

Porter, Gerard

2017-07-09

The relationship between the ethical standards for the governance of clinical trials and market forces can be complex and problematic. This article uses India as a case study to explore this nexus. From the mid-2000s, India became a popular destination for foreign-sponsored clinical trials. The Indian government had sought to both attract clinical trials and ensure these would be run in line with internationally accepted ethical norms. Reports of controversial medical research, however, triggered debate about the robustness and suitability of India's regulatory system. In response to civil society pressure and interventions by the Supreme Court, the Indian government proposed additional measures aimed at strengthening protections for clinical trial participants. Whilst the reforms can be seen as a victory for human rights activists, they have also been criticised as being overly burdensome for sponsors. Indeed, their announcement prompted an exodus of clinical trials from India. Fearful of losing business to 'rival' countries, the Indian government is revisiting some of its proposals. The Indian example suggests that research ethics frameworks and national policies for economic development are increasingly intertwined. Host countries are in theory free to improve the lot of research participants, but doing so may make them appear less attractive to foreign sponsors, who can simply shift their activities to more industry-friendly jurisdictions. Although these economic pressures are unlikely to lead to a regulatory 'race to the bottom', they may limit host countries' ability to enact socially desirable reforms. © 2017 John Wiley & Sons Ltd.

Novel ocular antihypertensive compounds in clinical trials

PubMed Central

Chen, June; Runyan, Stephen A; Robinson, Michael R

2011-01-01

Introduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary

Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications: the example of oncology trials.

PubMed

Perlmutter, A S; Tran, V-T; Dechartres, A; Ravaud, P

2017-04-01

Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [κ = 0.53, 95% confidence interval (0.25-0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of

A pilot survey of African-American physician perceptions about clinical trials.

PubMed

Lynch, G F; Gorelick, P B; Raman, R; Leurgans, S

2001-12-01

African Americans have been underrepresented in clinical trials. However, African-American physician attitudes about clinical trials may influence patient recruitment. We identified the perceptions of African-American physician members of the Cook County Physicians Association (CCPA) about clinical trials in the Chicago Metropolitan area using a self-administered questionnaire. An 18-item, 2-page survey that included information about physician demographics, practice type, and specialty, and perceptions regarding clinical research was sent to each of the 609 active or inactive members of the CCPA, a predominantly African-American physician organization. Each survey was accompanied by a letter of explanation and a self-addressed, return envelope. Data from the surveys were stored and analyzed in a database. A total of 166 members (27%) completed the survey. Fifty percent of the respondents were men and 50% were women. The mean age of the group was 45 years, and almost half had participated previously as a local investigator, or assisted on a clinical or laboratory study. Factors identified by the members as possibly being disadvantages to participation in a clinical trial, or factors influencing African-American recruitment included: (a) lack of patient awareness of clinical trials (93%); (b) patient mistrust of the medical community (92%); (c) additional administrative tasks in conjunction with a patient enrolled in a study (56%); (d) blind drug assignment (41.6%). African-American physicians perceive inherent disadvantages from participation in clinical trials and have pinpointed factors that may influence patient recruitment. These factors may be addressed by focused physician and community education.

Adaptive designs in clinical trials.

PubMed

Bowalekar, Suresh

2011-01-01

In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA)/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

Visual scoring of non cavitated caries lesions and clinical trial efficiency, testing xylitol in caries-active adults.

PubMed

Brown, John P; Amaechi, Bennett T; Bader, James D; Gilbert, Gregg H; Makhija, Sonia K; Lozano-Pineda, Juanita; Leo, Michael C; Chen, Chuhe; Vollmer, William M

2014-06-01

To better understand the effectiveness of xylitol in caries prevention in adults and to attempt improved clinical trial efficiency. As part of the Xylitol for Adult Caries Trial (X-ACT), non cavitated and cavitated caries lesions were assessed in subjects who were experiencing the disease. The trial was a test of the effectiveness of 5 g/day of xylitol, consumed by dissolving in the mouth five 1 g lozenges spaced across each day, compared with a sucralose placebo. For this analysis, seeking trial efficiency, 538 subjects aged 21-80, with complete data for four dental examinations, were selected from the 691 randomized into the 3-year trial, conducted at three sites. Acceptable inter- and intra-examiner reliability before and during the trial was quantified using the kappa statistic. The mean annualized noncavitated plus cavitated lesion transition scores in coronal and root surfaces, from sound to carious favoured xylitol over placebo, during the three cumulative periods of 12, 24, and 33 months, but these clinically and statistically nonsignificant differences declined in magnitude over time. Restricting the present assessment to those subjects with a higher baseline lifetime caries experience showed possible but inconsistent benefit. There was no clear and clinically relevant preventive effect of xylitol on caries in adults with adequate fluoride exposure when non cavitated plus cavitated lesions were assessed. This conformed to the X-ACT trial result assessing cavitated lesions. Including non cavitated lesion assessment in this full-scale, placebo-controlled, multisite, randomized, double-blinded clinical trial in adults experiencing dental caries did not achieve added trial efficiency or demonstrate practical benefit of xylitol. ClinicalTrials.Gov NCT00393055. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A National Cancer Clinical Trials Network: Recommendations from the Institute of Medicine

PubMed Central

Nass, Sharyl J.; Balogh, Erin; Mendelsohn, John

2010-01-01

Oncology has become one of the most active areas of drug discovery, with more than 800 cancer therapeutics in development. This presents an unprecedented opportunity to improve the outcome for patients with cancer, but also requires an effective and efficient clinical trials network to generate the evidence necessary for regulatory approval and optimal integration of new treatments into clinical care. The Clinical Trials Cooperative Group Program supported by the National Cancer Institute has been instrumental in establishing standards of care in oncology over the last 50 years, but it currently faces numerous challenges that threaten its ability to undertake the large-scale, multi-institutional trials that advance patient care. The Institute of Medicine recently appointed a consensus study committee to assess the organization and operation of the Cooperative Group Program and recommend ways to improve the quality of cancer clinical trials conducted by the Groups and others. The committee developed a set of recommendations, summarized here, that aim to improve the speed and efficiency of trials; incorporate innovative science and trial design; improve prioritization, selection, and support of trials; and increase participation by patients and physicians. PMID:21326081

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

A Brief Report of the Status of Central Nervous System Metastasis Enrollment Criteria for Advanced Non-Small Cell Lung Cancer Clinical Trials: A Review of the ClinicalTrials.gov Trial Registry.

PubMed

McCoach, Caroline E; Berge, Eamon M; Lu, Xian; Barón, Anna E; Camidge, D Ross

2016-03-01

Central nervous system (CNS) metastases are common in non-small cell lung cancer (NSCLC), yet clinical trials of new drugs in advanced NSCLC have varying inclusion and exclusion criteria for CNS disease. The true extent of variation in CNS-related enrollment criteria in NSCLC clinical trials has not been documented. We performed a systematic search of the ClinicalTrials.gov website to characterize interventional drug trials enrolling adult patients with advanced NSCLC. Of 413 open trials, 78 (19%) strictly excluded patients with leptomeningeal disease (LMD). Separate from LMD, patients with any history of CNS metastases were strictly excluded in 59 trials (14%), allowed after local treatment in 169 (41%), and allowed with no prior treatment in 106 (26%). No explicit mention of CNS disease was made in 79 trials (19%). In multivariate analysis looking at trial phase, location, sponsor, and treatment type, only sponsor was statistically significant, with pharmaceutical industry-sponsored trials having higher odds of excluding patients with brain metastases than did university or investigator-initiated trials (OR = 2.262, 95% confidence interval: 1.063-4.808, p = 0.0342) CONCLUSIONS: With 14% to 19% of trials excluding any history of LMD or CNS parenchymal metastatic disease and 41% of trials permitting CNS disease only after prior CNS-directed treatment, direct evidence of activity of a treatment on CNS disease cannot be reliably generated in most NSCLC trials. Given the high frequency of CNS disease in NSCLC and only sponsor being associated with specific CNS exclusion criteria, sponsors should consider tailoring trial designs to explore CNS benefit more explicitly. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

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.

Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials.

PubMed

Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D

2016-02-10

Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving

Review of ongoing clinical trials in non-small cell lung cancer: a status report for 2009 from the ClinicalTrials.gov website.

PubMed

Subramanian, Janakiraman; Madadi, Anusha R; Dandona, Monica; Williams, Kristina; Morgensztern, Daniel; Govindan, Ramaswamy

2010-08-01

Several new agents are being tested in clinical trials for patients with non-small cell lung cancer (NSCLC). A survey of ongoing clinical trials in NSCLC in the ClinicalTrials.gov website would help identify areas that require further attention in the future. We conducted a survey of ongoing clinical trials on NSCLC registered in the ClinicalTrials.gov website. The advanced search option was applied using the terms "non small cell lung cancer," "open studies," "interventional," and "adults 18 years or older." Of the 493 eligible trials, 77 (15.6%) were phase III, 92 (18.7%) were phase I, and 240 (48.7%) were phase II trials. Universities were listed as the primary sponsor for 224 (45.4%) trials and pharmaceutical industry for 166 (33.7%) trials. Majority of the trials were multicenter studies (56.8%) and were being conducted exclusively within the United States (51.3%). A large proportion of phase II and III clinical trials (77.2%) were focused on patients with advanced-stage disease. The most frequently used end points were progression-free survival (27.1%) followed by tumor response rate (22.9%) and overall survival (16.6%). Although biomarker analysis was included in 185 (37.5%) trials, only 39 (7.9%) trials used biomarkers for patient selection. Progression-free survival is the end point most commonly used to assess the effectiveness of experimental regimens, and biomarker-based patient selection is rarely used in ongoing clinical trials for NSCLC.

TU-G-BRB-02: Clinical Trials in Particle Therapy - Open Questions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choy, H.

2015-06-15

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. Themore » lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle

TU-G-BRB-00: Clinical Trials in Proton and Particle Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2015-06-15

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. Themore » lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle

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.

Clinical Trial Basics

MedlinePlus

... participate, in a study. These guidelines are called Inclusion/Exclusion Criteria . Factors that allow you to take part in a clinical trial are called "inclusion criteria." Those that exclude or prevent participation are " ...

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

PubMed

Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

2015-05-01

The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

An Argument for Fewer Clinical Trials.

PubMed

Borgerson, Kirstin

2016-11-01

The volume of clinical research is increasing exponentially-far beyond our ability to process and absorb the results. Given this situation, it may be beneficial to consider reducing the flow at its source. In what follows, I will motivate and critically evaluate the following proposal: researchers should conduct fewer clinical trials. More specifically, I c onsider whether researchers should be permitted to conduct only clinical research of very high quality and, in turn, whether research ethics committees (RECs) should prohibit all other, lower-quality research, even when it might appear to meet some minimal ethical standard. Following a close analysis of the social-value requirement of ethical clinical research, I argue that this proposal is defensible. The problem identified in this paper has two parts, quantity and quality, and some clarification is needed about the latter because "quality" is a highly contested term in the medical literature. When some scholars advocate for high-quality trials, they mean large-scale, simple, explanatory randomized controlled trials. Others, including myself, have defended a different characterization of high-quality research that tends more toward pragmatic trial design and the use of methods other than RCTs. Pragmatic trials aim to provide evidence that directly supports clinical decision-making in "usual" care settings. Unlike explanatory trials, which aim to abstract away from particular settings and patients, in the hopes of creating ideal conditions for the success of an intervention, pragmatic trials deliberately pursue knowledge of high applicability, through the use of representative subjects, clinically important questions, flexible treatment protocols, patient-oriented outcome measures, and so on. I see applicability as a marker of high-quality research. The context in which research is meant to be applied should be the context in which new interventions are evaluated. © 2016 The Hastings Center.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications-a cross-sectional study.

PubMed

Earley, Amy; Lau, Joseph; Uhlig, Katrin

2013-01-18

A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Registry-based study of clinical trial results reporting. ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.

Clinical trial designs incorporating predictive biomarkers☆

PubMed Central

Renfro, Lindsay A.; Mallick, Himel; An, Ming-Wen; Sargent, Daniel J.; Mandrekar, Sumithra J.

2016-01-01

Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer “targeted” drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research. PMID:26827695

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development

PubMed Central

Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho

2018-01-01

Background Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. Objective The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. Methods This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. Results In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully

Active Video Game Exercise Training Improves the Clinical Control of Asthma in Children: Randomized Controlled Trial

PubMed Central

Gomes, Evelim L. F. D.; Carvalho, Celso R. F.; Peixoto-Souza, Fabiana Sobral; Teixeira-Carvalho, Etiene Farah; Mendonça, Juliana Fernandes Barreto; Stirbulov, Roberto; Sampaio, Luciana Maria Malosá; Costa, Dirceu

2015-01-01

Objective The aim of the present study was to determine whether aerobic exercise involving an active video game system improved asthma control, airway inflammation and exercise capacity in children with moderate to severe asthma. Design A randomized, controlled, single-blinded clinical trial was carried out. Thirty-six children with moderate to severe asthma were randomly allocated to either a video game group (VGG; N = 20) or a treadmill group (TG; n = 16). Both groups completed an eight-week supervised program with two weekly 40-minute sessions. Pre-training and post-training evaluations involved the Asthma Control Questionnaire, exhaled nitric oxide levels (FeNO), maximum exercise testing (Bruce protocol) and lung function. Results No differences between the VGG and TG were found at the baseline. Improvements occurred in both groups with regard to asthma control and exercise capacity. Moreover, a significant reduction in FeNO was found in the VGG (p < 0.05). Although the mean energy expenditure at rest and during exercise training was similar for both groups, the maximum energy expenditure was higher in the VGG. Conclusion The present findings strongly suggest that aerobic training promoted by an active video game had a positive impact on children with asthma in terms of clinical control, improvementin their exercise capacity and a reductionin pulmonary inflammation. Trial Registration Clinicaltrials.gov NCT01438294 PMID:26301706

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

New male contraceptive entering clinical trials worldwide.

PubMed

1989-10-01

250 men are participating in a clinical trial of a reversible male testosterone contraceptive at the University of Washington in Seattle and at 9 other centers in Europe, Asia, and Australia. Clinicians inject the WHO-developed testosterone enanthate (200 mg) into these men once a week. The testosterone contraceptive instructs the pituitary gland to deactivate 2 hormones which normally maintain the testes' function resulting in a temporary stop of spermatogenesis just like the female oral contraceptive instructs the pituitary gland to suppress ovulation. Tests of 5 ejaculates in preliminary trials have indicated that 50-60% of the men experience azoospermia. Investigators are concerned with the possibility that ejaculates during normal intercourse may contain enough sperm to impregnate the partner. An investigator at the University of Washington believes this clinical trial of 250 men will determine whether this is indeed the case. The concern about contraceptive failure is the main problem with contraceptive testosterone. The minor side effects include weight gain which may be due to increased muscle mass and some sodium retention, acne, and possible reduction of libido but that has not yet occurred in the 250 men in the clinical trial. This contraceptive testosterone does not remain active for long periods of time if administered orally. Researchers are now developing a newer form of the contraceptive which will increase the intervals between administrations from 1 week to 3 months. An investigator from Seattle guesses that this male contraceptive will not be available for marketing in the US until at least 1994.

How redesigning AD clinical trials might increase study partners’ willingness to participate

PubMed Central

Karlawish, Jason; Cary, Mark S.; Rubright, Jonathan; TenHave, Tom

2008-01-01

Background: Timely recruiting and retaining participants into Alzheimer disease (AD) clinical trials is a challenge. We used conjoint analysis to identify how alterations in attributes of clinical trial design improve willingness to participate: risk, home visits, car service, or increased chance of receiving intervention. Method: A total of 108 study partners of patients with very mild to severe stage AD rated willingness to allow their relative to participate in eight clinical trials that varied combinations of the four attributes. Results: The highest utility was for home visits (0.89) which essentially compensated for the disutility of high risk (−0.85). The combination of home visits and car service was redundant, with almost no increase in utility over home visits alone. Seventeen percent were willing to participate in a trial with no amenities; the addition of home visits increased predicted willingness to participate to 27%; low risk, home visits, and higher chance of active treatment increased predicted willingness to 60%. The value of reducing the hassles of travel correlated well with measures of AD severity (activities of daily living r = 0.41, p < 0.001; basic activities of daily living r = 0.38, p < 0.001; Neuropsychiatric Inventory severity p = 0.24, p = 0.01; Neuropsychiatric Inventory distress r = 0.23, p < 0.02). No association was found between degree of study partner burden and willingness to tolerate risk of an intervention. Conclusion: Clinical trials that reduce travel inconvenience may offset the disincentive of study features such as the risk of intervention and may also increase willingness to participate. Redesigning trials may also help recruit patients with more severe Alzheimer disease. Shorter recruitment periods and increased retention rates may offset costs of these changes. GLOSSARY AD = Alzheimer disease; BLUP = best linear unbiased prediction; RAQ = Research Attitude Questionnaire. PMID:19047560

Ethics in clinical drug trial research in private practice.

PubMed

Beran, R G; Beran, M E

2006-09-01

Private clinics and clinicians have been involved in clinical drug trials for approximately two decades. This paper reviews the ethical consideration inherent in this process. Involvement of a single community based, private, Australian neurological clinic in the conduct of trials was audited. Changes in ethical considerations were analysed. The clinic previously audited its clinical trial involvement, starting with pharmaceutical company orchestrated trials. These were vetted by hospital based ethics committees (ECs) which then refused to review private research. A private EC accommodating NH & MRC standards was formed to assess private research. Indemnity concerns forced return to institutional ECs with government guaranteed indemnification. Trials evolved to investigator initiated, company sponsored studies thence a company asking the clinic to devise, sponsor and manage a trial. The latter relegated trial co-ordination to the clinic which would control publication thereby creating new ethical standards. Private practice trial involvement evolved from reluctant inclusion to a pivotal role in privately sponsored studies. Access to ECs is government endorsed and publication is independent for investigator-sponsored trials. There has been modification of standard operating procedures and enhanced ethical standards.

Clinical trial of sparfloxacin for lepromatous leprosy.

PubMed

Chan, G P; Garcia-Ignacio, B Y; Chavez, V E; Livelo, J B; Jimenez, C L; Parrilla, M L; Franzblau, S G

1994-01-01

Nine previously untreated patients with lepromatous leprosy were treated with 200 mg of sparfloxacin daily for 12 weeks to determine whether this drug is bactericidal for Mycobacterium leprae in humans. The efficacy of therapy was monitored both clinically and by measuring changes in morphological index, mouse footpad infectivity, and the radiorespirometric activity of M. leprae organisms obtained from serial biopsy specimens and also by determining titers of phenolic glycolipid-I in serum. Most patients showed clinical improvement within 2 weeks of treatment; this was accompanied by significant reductions in the morphological index, mouse footpad infectivity, and bacillary radiorespirometric activity. After 4 weeks of treatment, all patients had a morphological index of zero and specimens from most patients were noninfectious for mice, while the median decrease in radiorespirometric activity was > 99%. Overall results by the rapid radiorespirometric assay paralleled those of the mouse footpad and morphological index assays. Sparfloxacin given at 200 mg once daily appears to be rapidly bactericidal in humans, with activity similar to that observed in a previous clinical trial with 400 mg of ofloxacin.

Advances in the management of multiple sclerosis spasticity: recent clinical trials.

PubMed

Fernández, Oscar

2014-01-01

Most patients with multiple sclerosis (MS) experience spasticity as the clinical course evolves. Associated symptoms include (often painful) spasms, urinary dysfunction and sleep disturbances. THC:CBD oromucosal spray (Sativex®) is approved for symptom improvement in adult patients with moderate to severe MS-related spasticity who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. In pivotal clinical trials of THC:CBD oromucosal spray, a meaningful proportion of patients with treatment-resistant MS spasticity achieved clinically relevant improvement with active treatment versus placebo. The utility of a 4-week trial of therapy to identify patients who respond to treatment was demonstrated in an enriched-design study. THC:CBD oromucosal spray was well tolerated in these studies, with no evidence of effects typically associated with recreational cannabis use. In a subsequent post approval clinical trial, THC:CBD oromucosal spray had no statistically significant effect on cognition and mood compared with placebo. Moreover, after 50 weeks' treatment, approximately two-thirds of patients, physicians and caregivers reported improvement from baseline in spasticity based on global impressions of change. Key Messages: In phase III clinical trials, approximately one-third of MS patients with treatment-resistant spasticity had a clinically relevant and statistically significant response to THC:CBD oromucosal spray. In addition to a reduction in spasticity, responders experienced meaningful relief from associated symptoms. THC:CBD oromucosal spray was generally well tolerated and efficacy was maintained over the longer term. A post-approval clinical trial indicated no effect of THC:CBD oromucosal spray on cognition or mood after 50 weeks of use. © 2014 S. Karger AG, Basel.

Regulating trust in pediatric clinical trials.

PubMed

Pinxten, Wim; Nys, Herman; Dierickx, Kris

2008-12-01

The participation of minors in clinical trials is essential to provide safe and effective medical care to children. Because few drugs have been tested in children, pediatricians are forced to prescribe medications off-label with uncertain efficacy and safety. In this article, we analyze how the enrollment of minors in clinical trials is negotiated within relationships of mutual trust between clinicians, minors, and their parents. After a brief description of the problems associated with involving minors in clinical research, we consider how existing "relationships of trust" can be used as a place where the concerns of research subjects can be more fully discussed and addressed. Building on the tacit recognition of trust found in The European Clinical Trials Directive we make policy recommendations that allow for clearer, more ethically informed guidelines for enrolling minors in clinical research.

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

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.

Inside information: Financial conflicts of interest for research subjects in early phase clinical trials.

PubMed

Helft, Paul R; Ratain, Mark J; Epstein, Richard A; Siegler, Mark

2004-05-05

In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial.

Microbicide clinical trial adherence: insights for introduction.

PubMed

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

2013-04-08

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.

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.

OARSI Clinical Trials Recommendations: Hand imaging in clinical trials in osteoarthritis.

PubMed

Hunter, D J; Arden, N; Cicuttini, F; Crema, M D; Dardzinski, B; Duryea, J; Guermazi, A; Haugen, I K; Kloppenburg, M; Maheu, E; Miller, C G; Martel-Pelletier, J; Ochoa-Albíztegui, R E; Pelletier, J-P; Peterfy, C; Roemer, F; Gold, G E

2015-05-01

Tremendous advances have occurred in our understanding of the pathogenesis of hand osteoarthritis (OA) and these are beginning to be applied to trials targeted at modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply hand imaging assessments in disease modifying clinical trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for MRI); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications–a cross-sectional study

PubMed Central

Earley, Amy; Lau, Joseph; Uhlig,, Katrin

2013-01-01

Context A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. Objective To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Design Registry-based study of clinical trial results reporting. Setting ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. Selection criteria A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. Main outcome measure ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. Results In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Conclusions Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and

African American women's perceptions of cancer clinical trials

PubMed Central

Haynes-Maslow, Lindsey; Godley, Paul; Dimartino, Lisa; White, Brandolyn; Odom, Janice; Richmond, Alan; Carpenter, William

2014-01-01

Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trial participation among African Americans is significantly lower than Caucasians. This study engaged focus groups of 82 female African American cancer survivors or cancer caregivers, including those in better resourced, more urban areas and less resourced, more rural areas. Informed by an integrated conceptual model, the focus groups examined perceptions of cancer clinical trials and identified leverage points that future interventions may use to improve enrollment rates. Study findings highlight variation in community knowledge regarding cancer clinical trials, and the importance of community education regarding clinical trials and overcoming historical stigma associated with clinical research specifically and the health care system more generally. Study participants commented on the centrality of churches in their communities, and thus the promise of the church as loci of such education. Findings also suggested the value of informed community leaders as community information sources, including community members who have a previous diagnosis of cancer and clinical trial experience. The sample size and location of the focus groups may limit the generalizability of the results. Since the women in the focus groups were either cancer survivors or caregivers, they may have different experiences than nonparticipants who lack the close connection with cancer. Trust in the health system and in one's physician was seen as important factors associated with patient willingness to enroll in clinical trials, and participants suggested that physicians who were compassionate and who engaged and educated their patients would build important trust requisite for patient participation in clinical trials. PMID:24905181

[Why multi-national clinical trials now?--Industry perspective].

PubMed

Miki, Satoshi

2007-02-01

Clinical trial environment in Japan has issues such as high clinical development cost, resource-intensive and time-consuming preparation for clinical trial conduct in each clinical site, long "White Space" and slow speed in pt.recruitment. As a result of the Guideline revision in Nov., 2005, overseas' Phase III data is now usable as pivotal data for NDA submissions. Therefore, acceleration of "hollowing out of clinical trails for registration in Japan has been the significant concern. Under such circumstances, the possible solution would be to participate in the Multi-National Clinical Trials." While other Asian countries, EU and the US have rich precedents and experiences in conducting Multi-National Clinical Trials, Japan was left alone and other Asian countries do not need any collaboration with Japan. It is proposed that Japan take initiative to set up the network such as "Asian Clinical Trial Group" and collaborate with other Asian countries from the beginning of early stage development. Eventually, Asia should become the third region to create clinical evidence, same as to EU and the US.

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development.

PubMed

Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho; Kim, Tae Won

2018-04-24

Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and

Clinical trial design for orthodontists.

PubMed

Pandis, Nikolaos; Cobourne, Martyn T

2013-06-01

High-quality research should form the basis of all clinical practice. Randomized controlled trials currently provide the gold standard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics. Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome. The methods available to achieve true randomization, a fundamental component in the design of these trials, are also discussed. In addition, we focus on how to minimize bias in clinical research, not only during the design and management of a trial, but also when disseminating results. We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial. Finally, we emphasise the importance of accurate and transparent reporting, which facilitates correct communication and assessment of the evidence.

Perspectives on barriers and facilitators to minority recruitment for clinical trials among cancer center leaders, investigators, research staff, and referring clinicians: enhancing minority participation in clinical trials (EMPaCT).

PubMed

Durant, Raegan W; Wenzel, Jennifer A; Scarinci, Isabel C; Paterniti, Debora A; Fouad, Mona N; Hurd, Thelma C; Martin, Michelle Y

2014-04-01

The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority populations. Yet very little is known about the perceptions of individuals actively involved in minority recruitment to clinical trials within cancer centers. Therefore, the authors assessed the perspectives of cancer center clinical and research personnel on barriers and facilitators to minority recruitment. In total, 91 qualitative interviews were conducted at 5 US cancer centers among 4 stakeholder groups: cancer center leaders, principal investigators, research staff, and referring clinicians. All interviews were recorded and transcribed. Qualitative analyses of response data was focused on identifying prominent themes related to barriers and facilitators to minority recruitment. The perspectives of the 4 stakeholder groups were largely overlapping with some variations based on their unique roles in minority recruitment. Four prominent themes were identified: 1) racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation, 2) potential minority participants often face multilevel barriers that preclude them from being offered an opportunity to participate in a clinical trial, 3) facilitators at both the institutional and participant level potentially encourage minority recruitment, and 4) variation between internal and external trial referral procedures may limit clinical trial opportunities for racial and ethnic minorities. Multilevel approaches are needed to address barriers and optimize facilitators within cancer centers to enhance minority recruitment for cancer clinical trials. © 2014 American Cancer Society.

A disparity of words: racial differences in oncologist-patient communication about clinical trials.

PubMed

Eggly, Susan; Barton, Ellen; Winckles, Andrew; Penner, Louis A; Albrecht, Terrance L

2015-10-01

African Americans are consistently underrepresented in cancer clinical trials. Minority under-enrolment may be, in part, due to differences in the way clinical trials are discussed in oncology visits with African American vs. White patients. To investigate differences in oncologist-patient communication during offers to participate in clinical trials in oncology visits with African American and White patients. From an archive of video-recorded oncology visits, we selected all visits with African American patients that included a trial offer (n = 11) and a matched sample of visits with demographically/medically comparable White patients (n = 11). Using mixed qualitative-quantitative methods, we assessed differences by patient race in (i) word count of entire visits and (ii) frequency of mentions and word count of discussions of clinical trials and key elements of consent. Visits with African American patients, compared to visits with White patients, were shorter overall and included fewer mentions of and less discussion of clinical trials. Also, visits with African Americans included less discussion of the purpose and risks of trials offered, but more discussion of voluntary participation. African American patients may make decisions about clinical trial participation based on less discussion with oncologists than do White patients. Possible explanations include a less active communication style of African Americans in medical visits, oncologists' concerns about patient mistrust, and/or oncologist racial bias. Findings suggest oncologists should pay more conscious attention to developing the topic of clinical trials with African American patients, particularly purpose and risks. © 2013 John Wiley & Sons Ltd.

A longitudinal study of organizational formation, innovation adoption, and dissemination activities within the National Drug Abuse Treatment Clinical Trials Network

PubMed Central

Roman, Paul M.; Abraham, Amanda J.; Rothrauff, Tanja C.; Knudsen, Hannah K.

2010-01-01

The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This paper focuses on three dimensions of the CTN’s organizational functioning. First, a longitudinal dataset is used to examine the CTN’s formation as a network of inter-organizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered inter-organizational interaction over time. Second, adoption of buprenorphine and motivational incentives among the CTN’s affiliated CTPs is identified over three waves of data. While adoption is found to increase with CTPs’ CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs’ pursuit of the CTN’s dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future. PMID:20307795

A longitudinal study of organizational formation, innovation adoption, and dissemination activities within the National Drug Abuse Treatment Clinical Trials Network.

PubMed

Roman, Paul M; Abraham, Amanda J; Rothrauff, Tanja C; Knudsen, Hannah K

2010-06-01

The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This article focuses on three dimensions of CTN's organizational functioning. First, a longitudinal dataset is used to examine CTN's formation as a network of interorganizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered interorganizational interaction over time. Second, adoption of buprenorphine and motivational incentives among CTN's affiliated community treatment programs (CTPs) is examined over three waves of data. Although adoption is found to increase with CTPs' CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs' pursuit of the CTN's dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future.

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial

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

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

Clinical trials in crisis: four simple methodologic fixes

PubMed Central

Vickers, Andrew J.

2014-01-01

There is growing consensus that the US clinical trials system is broken, with trial costs and complexity increasing exponentially, and many trials failing to accrue. Yet concerns about the expense and failure rate of randomized trials are only the tip of the iceberg; perhaps what should worry us most is the number of trials that are not even considered because of projected costs and poor accrual. Several initiatives, including the Clinical Trials Transformation Initiative and the “Sensible Guidelines Group” seek to push back against current trends in clinical trials, arguing that all aspects of trials - including design, approval, conduct, monitoring, analysis and dissemination - should be based on evidence rather than contemporary norms. Proposed here are four methodologic fixes for current clinical trials. The first two aim to simplify trials, reducing costs and increasing patient acceptability by dramatically reducing eligibility criteria - often to the single criterion that the consenting physician is uncertain which of the two randomized arms is optimal - and by clinical integration, investment in data infrastructure to bring routinely collected data up to research grade to be used as endpoints in trials. The second two methodologic fixes aim to shed barriers to accrual, either by cluster randomization of clinicians (in the case of modifications to existing treatment) or by early consent, where patients are offered the chance of being randomly selected to be offered a novel intervention if disease progresses at a subsequent point. Such solutions may be partial, or result in a new set of problems of their own. Yet the current crisis in clinical trials mandates innovative approaches: randomized trials have resulted in enormous benefits for patients and we need to ensure that they continue to do so. PMID:25278228

Clinical trials in crisis: Four simple methodologic fixes.

PubMed

Vickers, Andrew J

2014-12-01

There is growing consensus that the US clinical trials system is broken, with trial costs and complexity increasing exponentially, and many trials failing to accrue. Yet, concerns about the expense and failure rate of randomized trials are only the tip of the iceberg; perhaps what should worry us most is the number of trials that are not even considered because of projected costs and poor accrual. Several initiatives, including the Clinical Trials Transformation Initiative and the "Sensible Guidelines Group" seek to push back against current trends in clinical trials, arguing that all aspects of trials-including design, approval, conduct, monitoring, analysis, and dissemination-should be based on evidence rather than contemporary norms. Proposed here are four methodologic fixes for current clinical trials. The first two aim to simplify trials, reducing costs, and increasing patient acceptability by dramatically reducing eligibility criteria-often to the single criterion that the consenting physician is uncertain which of the two randomized arms is optimal-and by clinical integration, investment in data infrastructure to bring routinely collected data up to research grade to be used as endpoints in trials. The second two methodologic fixes aim to shed barriers to accrual, either by cluster randomization of clinicians (in the case of modifications to existing treatment) or by early consent, where patients are offered the chance of being randomly selected to be offered a novel intervention if disease progresses at a subsequent point. Such solutions may be partial, or result in a new set of problems of their own. Yet, the current crisis in clinical trials mandates innovative approaches: randomized trials have resulted in enormous benefits for patients, and we need to ensure that they continue to do so. © The Author(s) 2014.

ClinicalTrials.gov Turns 10! | NIH MedlinePlus the Magazine

MedlinePlus

... please turn Javascript on. Feature: Clinical Trials ClinicalTrials.gov Turns 10! Past Issues / Fall 2010 Table of ... and whom to contact for more information. ClinicalTrials.gov's Helpful Features ClinicalTrials.gov has many helpful consumer ...

Huntington’s Disease Clinical Trials Corner: February 2018

PubMed Central

Rodrigues, Filipe B.; Wild, Edward J.

2018-01-01

In the second edition of the Huntington’s Disease Clinical Trials Corner we list all currently registered and ongoing clinical trials, summarise the top-line results of the recently-announced IONIS-HTTRX trial (NCT02519036), expand on Wave Life Sciences’ PRECISION-HD1 (NCT03225833) and PRECISION-HD2 (NCT03225846), and cover one recently finished trial: the FIRST-HD deutetrabenazine trial (NCT01795859). PMID:29480210

Searching ClinicalTrials.gov and the International Clinical Trials Registry Platform to inform systematic reviews: what are the optimal search approaches?

PubMed

Glanville, Julie M; Duffy, Steven; McCool, Rachael; Varley, Danielle

2014-07-01

Since 2005, International Committee of Medical Journal Editors (ICMJE) member journals have required that clinical trials be registered in publicly available trials registers before they are considered for publication. The research explores whether it is adequate, when searching to inform systematic reviews, to search for relevant clinical trials using only public trials registers and to identify the optimal search approaches in trials registers. A search was conducted in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for research studies that had been included in eight systematic reviews. Four search approaches (highly sensitive, sensitive, precise, and highly precise) were performed using the basic and advanced interfaces in both resources. On average, 84% of studies were not listed in either resource. The largest number of included studies was retrieved in ClinicalTrials.gov and ICTRP when a sensitive search approach was used in the basic interface. The use of the advanced interface maintained or improved sensitivity in 16 of 19 strategies for Clinicaltrials.gov and 8 of 18 for ICTRP. No single search approach was sensitive enough to identify all studies included in the 6 reviews. Trials registers cannot yet be relied upon as the sole means to locate trials for systematic reviews. Trials registers lag behind the major bibliographic databases in terms of their search interfaces. For systematic reviews, trials registers and major bibliographic databases should be searched. Trials registers should be searched using sensitive approaches, and both the registers consulted in this study should be searched.

Ethics of clinical trials.

PubMed

Palter, S F

1996-05-01

The modern clinical trial is a form of human experimentation. There is a long history of disregard for individual rights of the patient in this context, and special attention must be paid to ethical guidelines for these studies. Clinical trials differ in basic ways from clinical practice. Foremost is the introduction of outside interests, beyond those of the patient's health, into the doctor-patient therapeutic alliance. Steps must be taken to protect the interests of the patient when such outside influence exists. Kantian moral theory and the Hippocratic oath dictate that the physician must respect the individual patient's rights and hold such interests paramount. These principles are the basis for informed consent. Randomization of patients is justified when a condition of equipoise exists. The changing nature of health care delivery in the United States introduces new outside interests into the doctor-patient relationship.

Patient Engagement in Neurological Clinical Trials Design: A Conference Summary.

PubMed

Cobb, Enesha M; Meurer, William; Harney, Deneil; Silbergleit, Robert; Lake, Bray Patrick; Clark, Christina; Gipson, Debbie; Barsan, William

2015-12-01

The conference objectives included educating patients and advocates about clinical trials, educating the clinical research community about patient perspectives on participating in clinical trial design, and identifying strategies to increase participation in clinical trial design for neurological disorders. Observations were noted during a 1-day conference attended by patients, patient advocates, clinical trial staff, and investigators. The conference offered didactic sessions, small, and large group discussions. Conference participants were patients, patient advocates, clinical trial staff, students, and investigators interested in engaging patients in clinical trial design for neurological disorders. Conference participants were asked to consider lessons learned that could increase patient engagement in clinical trial design. We found that there is growing interest in including patients in the design of clinical trials for neurological disorders. Several themes emerged on how to move forward: networking; the multifaceted roles of advocates in research; training and education; creating patient-researcher partnerships; and clinical trials regulation issues. The conference provided a forum for dialogue regarding stakeholder engagement in the design of clinical trials for neurological disorders. This experience provides a template for replication and dissemination of this conference and informs next steps to accelerate the pathway from dialogue to action. © 2015 Wiley Periodicals, Inc.

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

PubMed

Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

2016-02-01

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

Researchers' views of the acceptability of restrictive provisions in clinical trial agreements with industry sponsors.

PubMed

Mello, Michelle M; Clarridge, Brian R; Studdert, David M

2005-01-01

We conducted a mail survey of 884 U.S. medical school faculty active in clinical research to elicit their views about the acceptability of provisions in contracts for industry-sponsored clinical trials that would restrict investigators' academic freedom and control over trials. We compared their responses to results from a similar survey of research administrators at 107 medical schools. There was substantial variation among clinical researchers in their acceptability judgments, with a relatively large proportion of clinical trial investigators willing to accept provisions that give industry sponsors considerable control over the dissemination of research results. There were significant differences in the perceptions of clinical trial investigators versus other recently published clinical researchers; investigators with a high versus low percentage of research support from industry; junior versus senior faculty; and investigators at institutions with high versus low National Institute of Health (NIH) funding ranks. There was also a significant divergence of views in a number of areas between clinical trialists and research administrators who negotiate clinical trial contracts on their behalf. Medical school faculty could benefit from additional guidance about what their institution views as acceptable parameters for industry-sponsored clinical trial agreements.

Pragmatic clinical trials: ethical imperatives and opportunities.

PubMed

Kalkman, Shona; van Thiel, Ghislaine J M W; Grobbee, Diederick E; van Delden, Johannes J M

2018-06-12

Pragmatic clinical trials generate robust real-world evidence that holds great potential to better inform decision making regarding new medicines. For clinicians, patients and regulators, this evidence would preferably be available sooner rather than later. This means that, ideally, market authorization of any given medicine is accompanied by evidence obtained from a pragmatic trial. Given the operational and regulatory complexities of pragmatic trials in general, stakeholders tend to be hesitant to employ more pragmatism at the time of market approval. One prominent hurdle for the conduct of pragmatic trials is the concern that pragmatic design features conflict with ethical standards for clinical trials. To encourage timely yet responsible generation of real-world evidence through clinical trials, it is important to delineate exactly which areas, from a societal point of view, demand early pragmatic evaluations. We also urge stakeholders to recognize how the current system of trial ethics oversight already accommodates for more-pragmatic approaches, and how new ideas about their permissibility have progressed in the bioethics literature. Copyright © 2018. Published by Elsevier Ltd.

TU-C-9A-01: IROC Organization and Clinical Trial Credentialing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Followill, D; Molineu, A; Xiao, Y

2014-06-15

As a response to recommendations from a report from the Institute of Medicine, NCI is reorganizing it clinical trial groups into a National Clinical Trial Network (NCTN) that consists of four adult groups (Alliance, ECOGACRIN, NRG, and SWOG) and one children’s group (COG). NRG will house CIRO, a center to promote innovative radiation therapy research and intergroup collaboration in radiation. The quality assurance groups that support clinical trials have also been restructured. ITC, OSU Imaging corelab, Philadelphia Imaging core-lab, QARC, RPC, and RTOGQA have joined together to create the Imaging and Radiation Oncology Core (IROC) Group. IROC’s mission is tomore » provide integrated radiation oncology and diagnostic imaging quality control programs in support of the NCI’s NCTN thereby assuring high quality data for clinical trials designed to improve the clinical outcomes for cancer patients worldwide. This will be accomplished through five core services: site qualification, trial design support, credentialing, data management, case review.These changes are important for physicist participating in NCI clinical trials to understand. We will describe in detail the IROC’s activities and five core services so that as a user, the medical physicist can learn how to efficiently utilize this group. We will describe common pitfalls encountered in credentialing for current protocols and present methods to avoid them. These may include the which benchmarks are required for NSABP B-51/RTOG 1304 and how to plan them as well as tips for phantom planning. We will explain how to submit patient and phantom cases in the TRIAD system used by IROC. Learning Objectives: To understand the basic organization of IROC, its mission and five core services To learn how to use TRIAD for patient and phantom data submission To learn how to avoid common pitfalls in credentialing for current trials.« less

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti‐neutrophil cytoplasm antibody‐associated vasculitis

PubMed Central

Hellmich, Bernhard; Flossmann, Oliver; Gross, Wolfgang L; Bacon, Paul; Cohen‐Tervaert, Jan Willem; Guillevin, Loic; Jayne, David; Mahr, Alfred; Merkel, Peter A; Raspe, Heiner; Scott, David G I; Witter, James; Yazici, Hasan; Luqmani, Raashid A

2007-01-01

Objectives To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Methods An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence‐based and expert opinion‐based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. Results Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti‐neutrophil cytoplasm antibody‐associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis‐specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. Conclusions On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well‐designed research in non‐AAV systemic vasculitides. PMID:17170053

Barriers to participation in clinical trials: a physician survey.

PubMed

Mahmud, A; Zalay, O; Springer, A; Arts, K; Eisenhauer, E

2018-04-01

Clinical trials are vital for evidence-based cancer care. Oncologist engagement in clinical trials has an effect on patient recruitment, which in turn can affect trial success. Identifying barriers to clinical trial participation might enable interventions that could help to increase physician participation. To assess factors affecting physician engagement in oncology trials, a national survey was conducted using the online SurveyMonkey tool (SurveyMonkey, San Mateo, CA, U.S.A.; http://www.surveymonkey.com). Physicians associated with the Canadian Cancer Clinical Trials Network and the Canadian Cancer Trials Group were asked about their specialty, years of experience, barriers to participation, and motivating interventions, which included an open-ended question inviting survey takers to suggest interventions. The survey collected 207 anonymous responses. Respondents were predominantly medical oncologists (46.4%), followed by radiation oncologists (24.6%). Almost 70% of the respondents had more than 10 years of experience. Significant time constraints included extra paperwork (77%), patient education (54%), and extended follow-up or clinic visits (53%). Timing of events within trials was also a barrier to participation (55%). Most respondents favoured clinical work credits (72%), academic credits (67%), a clinical trial alert system (75%), a regular meeting to review trial protocols (65%), and a screening log to aid in patient accrual (67%) as motivational strategies. Suggested interventions included increased support staff, streamlined regulatory burden, and provision of greater funding for trials and easier access to ancillary services. The present study confirms that Canadian oncologists are willing to participate in clinical research, but face multiple barriers to trial participation. Those barriers could be mitigated by the implementation of several interventions identified in the study.

Clinical Trials Information for Patients and Caregivers

MedlinePlus

... to Ask about Your Treatment Research Clinical Trials Information for Patients and Caregivers Clinical trials are research ... Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp Online Chat MORE INFORMATION About ...

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

Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Yang, Guoyan; Wang, Yuyi; Tian, Jinzhou; Liu, Jian-Ping

2013-01-01

Background Huperzine A is a Chinese herb extract used for Alzheimer’s disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer’s disease. Methods We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer’s disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249) Results 20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A. Conclusions Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease. However, the findings should be interpreted with caution due to the poor methodological quality of the

Health literacy and usability of clinical trial search engines.

PubMed

Utami, Dina; Bickmore, Timothy W; Barry, Barbara; Paasche-Orlow, Michael K

2014-01-01

Several web-based search engines have been developed to assist individuals to find clinical trials for which they may be interested in volunteering. However, these search engines may be difficult for individuals with low health and computer literacy to navigate. The authors present findings from a usability evaluation of clinical trial search tools with 41 participants across the health and computer literacy spectrum. The study consisted of 3 parts: (a) a usability study of an existing web-based clinical trial search tool; (b) a usability study of a keyword-based clinical trial search tool; and (c) an exploratory study investigating users' information needs when deciding among 2 or more candidate clinical trials. From the first 2 studies, the authors found that users with low health literacy have difficulty forming queries using keywords and have significantly more difficulty using a standard web-based clinical trial search tool compared with users with adequate health literacy. From the third study, the authors identified the search factors most important to individuals searching for clinical trials and how these varied by health literacy level.

Is Religiosity Related to Attitudes Towards Clinical Trials Participation?

PubMed Central

Daverio-Zanetti, Svetlana; Schultz, Kathryn; del Campo, Miguel A. Martin; Malcarne, Vanessa; Riley, Natasha; Sadler, Georgia Robins

2014-01-01

Research indicates that a low percentage of cancer patients enroll in cancer clinical trials. This is especially true among minority groups such as Hispanic Americans. Considering the importance of religion in the Hispanic American community, it is important to understand its relationship to perceptions of clinical trials. Five hundred and three Latina women completed the Barriers to Clinical Trials Participation Scale and the Duke University Religion Index. For the total sample, higher organizational and intrinsic religiosity were significantly associated with perceived lack of community support for clinical trials participation. In subgroup analysis, the relationship between organizational religiosity and lack of support was stronger among Latinas who were Spanish language-preference, and Latinas who were Catholic. Intrinsic religiosity was associated with mistrust among Spanish language-preference Latinas, and both organizational and intrinsic religiosity were associated with lack of familiarity with clinical trials among Christian (non-Catholic) Latinas. These results indicate religious institutions that serve Latinas may be an effective venue for disseminating clinical trial education programs to improve attitudes toward clinical trials participation. PMID:24953236

Clinical trials and the new good clinical practice guideline in Japan. An economic perspective.

PubMed

Ono, S; Kodama, Y

2000-08-01

Japanese clinical trials have been drastically changing in response to the implementation of the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guideline in 1997. The most important aim of the new guideline is to standardise the quality of clinical trials in the US, European Union and Japan, but it inevitably imposes substantial costs on investigators, sponsors and even patients in Japan. The study environment in Japan differs from that in the US in several ways: (i) historical lack of a formal requirement for informed consent; (ii) patients' attitudes to clinical trials in terms of expectation of positive outcomes; (iii) the implications of universal health insurance for trial participation; (iv) the historical absence of on-site monitoring by the sponsor, with the attendant effects on study quality; and (v) the lack of adequate financial and personnel support for the conduct of trials. Implementation of the new GCP guideline will improve the ethical and scientific quality of trials conducted in Japan. It may also lead to an improved relationship between medical professionals and patients if the requirement for explicit informed consent in clinical trials leads to the provision of a similar level of patient information in routine care and changes the traditional paternalistic attitude of physicians to patients. The initial response of the Japanese 'market' for clinical trials to the implementation of the ICH-GCP guideline has been clinical trial price increases and a decrease in the number of study contracts. These changes can be explained by applying a simple demand-supply scheme. Whether clinical trials undertaken in Japan become more or less attractive to the industry in the long term will depend on other factors such as international regulations on the acceptability of foreign clinical trials and the reform of domestic healthcare policies.

Performance of Crohn's disease Clinical Trial Endpoints based upon Different Cutoffs for Patient Reported Outcomes or Endoscopic Activity: Analysis of EXTEND Data.

PubMed

Feagan, Brian; Sandborn, William J; Rutgeerts, Paul; Levesque, Barrett G; Khanna, Reena; Huang, Bidan; Zhou, Qian; Maa, Jen-Fue; Wallace, Kori; Lacerda, Ana; Thakkar, Roopal B; Robinson, Anne M

2018-04-23

Clinical trial endpoints for Crohn's disease (CD) activity correlate poorly with mucosal inflammation; to assess treatment efficacy, patient-reported outcomes and endoscopic assessments are preferred. This study assessed the impact on treatment efficacy estimations of using different definitions of clinical and endoscopic remission and endoscopic response, and of using site- or central-based endoscopy evaluation. This post hoc analysis of data fromEXTEND (extend the safety and efficacy of adalimumab through endoscopic healing), a placebo (PBO)-controlled, randomized trial of adalimumab (ADA) for mucosal healing, included adults with moderate-to-severe CD. Subsets of patients meeting specified Simplified Endoscopic Score for CD (SES-CD) inclusion criteria, according to site or central reading, and baseline stool frequency (SF) and/or abdominal pain score (AP) thresholds were evaluated. Various endpoint definitions based on the Crohn's Disease Activity Index (CDAI), its SF and AP components, SES-CD, and composite endpoints were compared between treatment groups. Increased stringency of Week 12 clinical endpoints compared to CDAI<150 to SF≤3.0/1.5&AP≤1.0 reduced PBO response rates by ≥12% and increased treatment effects by ≤10%. Amending the SES-CD endpoint from ≤4 to ≤2 reduced the treatment effect from 24% to 8%. Composite endpoints further diminished response rates and effect sizes. Site-based evaluation was associated with lower remission rates versus central reading in the PBO group and, thus, greater ADA-related treatment effects. This analysis is the first to demonstrate that increasing the stringency of clinical and endoscopic endpoint definitions in CD trials, especially lowering SF or SES-CD definitions, reduces the ability to detect treatment-related change in CD activity; focus on endpoints that reflect clinical change is warranted.

[Basic principles, planning and implementation of non-commercial clinical trials].

PubMed

Finger, R P; Coch, C; Coenen, M; Mengel, M; Hartmann, G; Holz, F G

2011-01-01

The proof of a drug's efficacy in randomized controlled trials is fundamental to therapeutic concepts determined by evidence-based medicine. Clinical trials according to the German Medicinal Products Act are performed by the pharmaceutical industry as company-sponsored trials (CST) driven by commercial interests or by non-commercial facilities as investigator-initiated trials (IIT), typically implemented by University Hospitals. In areas with no commercial interest, IITs are the driving force that generate scientific progress leading to treatment optimization. Therefore, non-commercial or investigator-initiated clinical trials are indispensable for improving medical care. To ensure the safety of trial participants and the quality of the data obtained, clinical trials are controlled by many legal regulations and internationally accepted quality standards. Therefore implementation of a clinical trial requires profound knowledge, qualified personnel, appropriate infrastructure, and substantial financial resources. In IITs unlike CSTs this has to be accomplished by the University without the assistance of the pharmaceutical industry. Since teaching of skills needed to perform clinical trials is still largely neglected in medical school and during residency this review addresses the (in clinical trials) inexperienced physician and outlines the characterization of a clinical trial, the range and division of responsibilities and the performance of clinical trials according to the German Medicinal Products Act.

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.

Clinical trial participation. Viewpoints from racial/ethnic groups.

PubMed

Roberson, N L

1994-11-01

Racial/ethnic groups' participation in clinical trials is a relatively new area of research that warrants attention. Although racial/ethnic groups have been included in experimental studies since the 1940s, they were not included in significant numbers in clinical trials for cancer. Clinical trials play a dominant role in clinical oncology. Despite this state-of-the-art cancer treatment, however, there is mounting concern that this scientific progress is not being shared equitably by all segments of the U.S. population. There is underrepresentation of members of racial/ethnic groups in cancer clinical trials, which suggests that participation may be a critical issue. Unfortunately, little is known or documented about these groups' participation in clinical trials. This paper discusses racial/ethnic groups' views and opinions about clinical trial participation. Diagnostic research was conducted as a beginning phase to investigate this new area of research. African Americans, Hispanics, and Native Americans in three Buffalo, New York, communities were selected as study subjects. Data were collected via telephone surveys. Qualitative methods were employed for data analysis and reporting. Findings showed that study subjects knew little about cancer clinical trials and basically had no opportunity to participate. They believed that participation in clinical trials could be beneficial. In each of the three groups, however, there were cultural factors believed to influence participation. A primary concern was "mistrust of white people" and the feeling of being treated like "guinea pigs." Based on study findings, it was evident that recruitment for improving participation requires strategic planning that involves participants representative of the study population. To yield results, the plan should be tailored to the target group, presented as a credible study, designed to reflect trust in the medical care team, and implemented through a continuous educational process.

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

Specific barriers to the conduct of randomised clinical trials on medical devices.

PubMed

Neugebauer, Edmund A M; Rath, Ana; Antoine, Sunya-Lee; Eikermann, Michaela; Seidel, Doerthe; Koenen, Carsten; Jacobs, Esther; Pieper, Dawid; Laville, Martine; Pitel, Séverine; Martinho, Cecilia; Djurisic, Snezana; Demotes-Mainard, Jacques; Kubiak, Christine; Bertele, Vittorio; Jakobsen, Janus C; Garattini, Silvio; Gluud, Christian

2017-09-13

Medical devices play an important role in the diagnosis, prevention, treatment and care of diseases. However, compared to pharmaceuticals, there is no rigorous formal regulation for demonstration of benefits and exclusion of harms to patients. The medical device industry argues that the classical evidence hierarchy cannot be applied for medical devices, as randomised clinical trials are impossible to perform. This article aims to identify the barriers for randomised clinical trials on medical devices. Systematic literature searches without meta-analysis and internal European Clinical Research Infrastructure Network (ECRIN) communications taking place during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. In addition to the barriers that exist for all trials, we identified three major barriers for randomised clinical trials on medical devices, namely: (1) randomisation, including timing of assessment, acceptability, blinding, choice of the comparator group and considerations on the learning curve; (2) difficulties in determining appropriate outcomes; and (3) the lack of scientific advice, regulations and transparency. The present review offers potential solutions to break down the barriers identified, and argues for applying the randomised clinical trial design when assessing the benefits and harms of medical devices.

Patient-Reported Outcome Measures for Use in Clinical Trials and Clinical Practice in Inflammatory Bowel Diseases: A Systematic Review.

PubMed

de Jong, Marin J; Huibregtse, Roxanne; Masclee, Ad A M; Jonkers, Daisy M A E; Pierik, Marie J

2018-05-01

Mucosal inflammation must be carefully monitored to improve the long-term outcomes of patients with inflammatory bowel diseases (IBD). Patient-reported outcome measures (PROMs) are used increasingly to monitor disease activity in clinical practice and as endpoints in clinical trials. We performed a systematic review to provide an overview of the available PROMs on IBD activity and to evaluate their diagnostic value. A systematic search of the PubMed, Medline, Cochrane library, and Embase databases using defined keywords, identified 973 articles. These were screened by 2 independent reviewers, and 37 articles on development or validation of PROMs to assess IBD activity were identified for further analysis. Based on the recommendations of the Food and Drug Administration (FDA), the following measurement properties were evaluated: content, construct, and criterion validity; reliability; and responsiveness to change. In addition, data on ease of use in clinical practice were collected. Seventeen articles presenting 20 different PROMs were included the final analysis, although none met all the FDA-recommended criteria. Only 2 PROMs (patient-reported Harvey Bradshaw Index and Simple Clinical Colitis Activity Index scores) reported patient involvement during its development. Only 6 PROMs (patient-reported global assessment, patient assessment of disease activity, mobile health index for Crohn's disease, mobile health index for ulcerative colitis, patient-reported outcome derived from the Mayo score, and the 6-point Mayo score) were validated as markers of IBD activity, using findings from endoscopy as the reference standard; these PROMs identified patients with mucosal inflammation with area under the curve values of 0.63-0.82. The mobile health index for CD and UC scores had the best measurement properties for use in clinical practice and in clinical trials. In a systematic review, we identified more than 20 PROMS that have been developed and tested for their ability to

Inept media trials of clinical trials

PubMed Central

Ramamurthy, N. V.

2012-01-01

The Indian media in general, with the exception of a few domain expert journalists, have failed to comprehend the complexities involved in the clinical trial process. In the run up to the deadline-based coverage of a story, a majority of them fall short in conveying the right perspective to readers, but nevertheless they have been successful in sensationalizing an event in this arena. Possibly by unintended misrepresentation, or mostly out of ignorance of the nuances involved in the clinical trials process, the media has done more harm than good, and got away with it. On the other side, the industry has been reluctant to engage with the media in a meaningful dialog for too long now. It bears not only the consequences of damage to its professional reputation following such reportage, but also the repercussions of unnecessary clampdowns by the regulators. Science journalism in India has yet to rise as a profession. PMID:22701819

Unfulfilled translation opportunities in industry sponsored clinical trials.

PubMed

Smed, Marie; Getz, Kenneth A

2013-05-01

Knowledge generated by site representatives through their participation in clinical trials is valuable for testing new products in use and obtaining final market approval. The leverage of this important knowledge is however challenged as the former direct relationships between in-house staff in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract Research Organization) and thereby adding another link in the relationships between site and sponsor. These changes are intended to optimize the time-consuming and costly trial phases; however, there is a need to study whether valuable knowledge and experience is compromised in the process. Limited research exists on the full range of clinical practice insights obtained by investigators during and after clinical trials and how well these insights are transferred to study sponsors. This study explores the important knowledge-transfer processes between sites and sponsors and to what extent sites' knowledge gained in clinical trials is utilized by the industry. Responses from 451 global investigative site representatives are included in the study. The analysis of the extensive dataset reveals that the current processes of collaboration between sites and the industry restrict the leverage of valuable knowledge gained by physicians in the process of clinical trials. These restrictions to knowledge-transfer between site and sponsor are further challenged if CRO partners are integrated in the trial process. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical trials of a personal electrocardiograph

NASA Astrophysics Data System (ADS)

Boyakhchyan, A.; Lezhnina, I.; Overchuk, K.; Perchatkin, V.; Lvova, A.; Alexander, U.

2018-05-01

The article describes the results of a clinical trial at the Cardiology Research Institute in Tomsk. Clinical trials were conducted to identify different important information for diagnosis. These tests were also conducted to remotely monitor the treatment of patients who had already been discharged from the hospital.The study involved 15 patients, the most interesting cases are described in this article.

Recruitment of subjects into clinical trials for Alzheimer disease.

PubMed

Knebl, Janice A; Patki, Deepti

2010-09-01

Alzheimer disease is a devastating neurodegenerative disorder affecting millions of Americans. It reduces the ability of the individual to remain independent, places a burden on caregivers, and substantially increases healthcare costs. New treatments are being tested in numerous clinical trials with the goal of preventing or delaying the onset of Alzheimer disease, slowing or modifying the disease's course, or finding a cure for patients with the disease. Alzheimer disease research can successfully proceed only if individuals who have this illness are willing to participate in clinical trials. However, recruitment and retention of subjects in clinical trials for Alzheimer disease is a challenging task. Furthermore, because of reductions in decision-making capacities of individuals with Alzheimer disease, clinical trials also need to involve caregivers. The present article delineates unique hurdles encountered in the recruitment process for Alzheimer disease clinical trials. The article also identifies strategies for effective recruitment of subjects in Alzheimer disease clinical trials, including guidelines to help principal investigators and clinical research coordinators reach recruitment goals.

Where are clinical trials going? Society and clinical trials.

PubMed

Sleight, P

2004-02-01

Clinical trials now increasingly impinge on society at large. First there is growing emphasis from health organizations on the need for unbiased evidence about the effectiveness of promoted remedies. Second, as most novel treatments accrue increased costs to society, these need to be evaluated in terms of value for money. Third, there has been confusion and concern about the resolution of conflicting evidence, especially the role of advertising and commercial pressures from a powerful pharmaceutical industry motivated by profit. Fourth, there is concern about research fraud and the ethics of clinical trials. Fifth, there is increasing suspicion of political advice, which sometimes has sought to reassure an anxious public on the basis of complex and possibly inadequate scientific information. Some of these issues are addressed by truly independent and properly constituted data and safety monitoring committees, which are of particular importance when academic investigators or universities have a large financial conflict of interest. This is now more problematic with the current encouragement of investigator-led spin-off companies. These issues are best resolved by independent financial support (from government or other institutions) rather than relying on the commercial sponsor.

The role and potential contribution of clinical research nurses to clinical trials.

PubMed

Spilsbury, Karen; Petherick, Emily; Cullum, Nicky; Nelson, Andrea; Nixon, Jane; Mason, Su

2008-02-01

This study explores the scope and potential contribution of the Clinical Research Nurse (CRN) role to clinical trials of a nursing-specific topic. Over the past two decades, there have been increases in the numbers of nurses working as CRNs because of the increasing global demand for clinical trials. CRNs can influence the quality of clinical trials but the scope and contribution of the role to clinical trials is not known. Qualitative focus group study. A focus group interview was carried out with CRNs (n = 9) employed on a large, multi-centre (six NHS Trusts) randomized controlled trial of pressure area care. The focus group interview was recorded, alongside field notes of participant interactions and behaviours, and transcribed verbatim. Data were analysed for thematic content and process. CRNs described their transition to a clinical research role. They reported a lack of confidence, role conflict as researcher and nurse, the challenges of gaining cooperation of clinical nursing staff to comply with trial protocols and difficulties maintaining their own motivation. CRNs provided their perceptions and observations of pressure area care and prevention. They identified areas of inadequate treatment, management and care, influenced by organizational and clinical aspects of care delivery. The study reveals challenges associated with training and management of CRNs. CRNs are usually associated with trial recruitment and data collection. This study highlights the additional contributions of CRNs for the study of topics specific to nursing as the result of their unique placement in the research centres as informal 'participant observers.' Such observations enhance understanding of the contexts being studied. These findings are relevant to the design and conduct of research studies of nursing care and practice and present ways for investigators to optimize the skills and knowledge of nurses working as CRNs.

Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis.

PubMed

Tupasi, Thelma; Gupta, Rajesh; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

2016-02-01

New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.

Phytochemistry, pharmacology, and clinical trials of Morus alba.

PubMed

Chan, Eric Wei-Chiang; Lye, Phui-Yan; Wong, Siu-Kuin

2016-01-01

The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy.

PubMed

Peay, Holly L; Tibben, Aad; Fisher, Tyler; Brenna, Ethan; Biesecker, Barbara B

2014-02-01

The social context of rare disease research is changing, with increased community engagement around drug development and clinical trials. This engagement may benefit patients and families but may also lead to heightened trial expectations and therapeutic misconception. Clinical investigators are also susceptible to harboring high expectations. Little is known about parental motivations and expectations for clinical trials for rare pediatric disorders. We describe the experience of parents and clinical investigators involved in a phase II clinical trial for Duchenne and Becker muscular dystrophy: their expectations, hopes, motivations, and reactions to the termination of the trial. This qualitative study was based on interviews with clinical investigators and parents of sons with Duchenne and Becker muscular dystrophy (DBMD) who participated in the phase IIa or IIb ataluren clinical trial in the United States. Interviews were transcribed and coded for thematic analysis. Participants were 12 parents of affected boys receiving active drug and 9 clinical investigators. High trial expectations of direct benefit were reported by parents and many clinicians. Investigators described monitoring and managing parents' expectations; several worried about their own involvement in increasing parents' expectations. Most parents were able to differentiate their expectations from their optimistic hopes for a cure. Parents' expectations arose from other parents, advocacy organizations, and the sponsor. All parents reported some degree of clinical benefit to their children. Secondary benefits were hopefulness and powerful feelings associated with active efforts to affect the disease course. Parents and clinical investigators reported strong, close relationships that were mutually important. Parents and clinicians felt valued by the sponsor for the majority of the trial. When the trial abruptly stopped, they described loss of engagement, distress, and feeling unprepared for the

Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy

PubMed Central

Peay, Holly L; Tibben, Aad; Fisher, Tyler; Brenna, Ethan; Biesecker, Barbara B

2014-01-01

Background The social context of rare disease research is changing, with increased community engagement around drug development and clinical trials. This engagement may benefit patients and families, but may also lead to heightened trial expectations and therapeutic misconception. Clinical investigators are also susceptible to harboring high expectations. Little is known about parental motivations and expectations for clinical trials for rare pediatric disorders. Purpose We describe the experience of parents and clinical investigators involved in a phase II clinical trial for Duchenne and Becker muscular dystrophy: their expectations, hopes, motivations, and reactions to the termination of the trial. Methods This qualitative study was based on interviews with clinical investigators and parents of sons with DBMD who participated in the phase IIa or IIb ataluren clinical trial in the United States. Interviews were transcribed and coded for thematic analysis. Results Participants were twelve parents of affected boys receiving active drug and nine clinical investigators. High trial expectations of direct benefit were reported by parents and many clinicians. Investigators described monitoring and managing parents’ expectations; several worried about their own involvement in increasing parents’ expectations. Most parents were able to differentiate their expectations from their optimistic hopes for a cure. Parents’ expectations arose from other parents, advocacy organizations, and the sponsor. All parents reported some degree of clinical benefit to their children. Secondary benefits were hopefulness and powerful feelings associated with active efforts to affect the disease course. Parents and clinical investigators reported strong, close relationships that were mutually important. Parents and clinicians felt valued by the sponsor for the majority of the trial. When the trial abruptly stopped, they described loss of engagement, distress, and feeling unprepared for

Trials with errors--preserving the integrity of clinical trials.

PubMed

Guyer, R L

2000-01-01

The crucial final test of medical research is the clinical trial, which determines whether a drug or discovery really is an effective therapy. All people who participate in clinical trials--researchers, sponsors, volunteers, analysts, reviewers, overseers, others--have opportunities to strengthen or weaken the integrity of the trial system by their behavior. Medical research is now officially married to business, and "profitable" connotes something different to each partner. Only if research and business can profit in parallel will the alliance succeed. Every person who is involved in the medical research business faces temptations and must choose how to react. Each has power and must choose how to wield it. Several centuries before this marriage, the Englishman Izaak Walton noted that "Health is...a blessing that money cannot buy."

Real-Time Enrollment Dashboard For Multisite Clinical Trials.

PubMed

Mattingly, William A; Kelley, Robert R; Wiemken, Timothy L; Chariker, Julia H; Peyrani, Paula; Guinn, Brian E; Binford, Laura E; Buckner, Kimberley; Ramirez, Julio

2015-10-30

Achieving patient recruitment goals are critical for the successful completion of a clinical trial. We designed and developed a web-based dashboard for assisting in the management of clinical trial screening and enrollment. We use the dashboard to assist in the management of two observational studies of community-acquired pneumonia. Clinical research associates and managers using the dashboard were surveyed to determine its effectiveness as compared with traditional direct communication. The dashboard has been in use since it was first introduced in May of 2014. Of the 23 staff responding to the survey, 77% felt that it was easier or much easier to use the dashboard for communication than to use direct communication. We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system.

Brief report: enhancement of patient recruitment in rheumatoid arthritis clinical trials using a multi-biomarker disease activity score as an inclusion criterion.

PubMed

van Vollenhoven, Ronald F; Bolce, Rebecca; Hambardzumyan, Karen; Saevarsdottir, Saedis; Forslind, Kristina; Petersson, Ingemar F; Sasso, Eric H; Hwang, C C; Segurado, Oscar G; Geborek, Pierre

2015-11-01

Rheumatoid arthritis (RA) clinical trials often exclude patients who have low C-reactive protein (CRP) levels, which slows enrollment into the trial. The purpose of this study was to determine whether high Multi-Biomarker Disease Activity (MBDA) scores (>44) in RA patients with low CRP levels (≤10 mg/liter) could be used as a complement to CRP levels >10 mg/liter to enhance patient recruitment without affecting clinical trial outcomes. We evaluated patients from the Swedish Pharmacotherapy (SWEFOT) trial, which did not include any selection criteria for CRP levels. Clinical outcomes were assessed after 3 months of methotrexate (MTX) monotherapy in MTX-naive RA patients (n = 220) and after 3-10 months of add-on therapy in patients who were incomplete responders to MTX alone (MTX-IR) (n = 127). Radiographic outcomes were assessed at 1 year in all patients. Within each cohort, the outcomes were compared between patients with a CRP level of ≤10 mg/liter and an MBDA score of >44 at the start of the respective treatment interval versus those with a CRP level of >10 mg/liter. Patients with both a CRP level of ≤10 mg/liter and an MBDA score of >44 at baseline had clinical and radiographic outcomes that were comparable to those in patients with a CRP level of >10 mg/liter at baseline. This broadened definition of the inclusion criteria identified an additional 24% of patients in the MTX-naive cohort and 47% in the MTX-IR cohort. Patient recruitment into RA clinical trials may be substantially enhanced, without any decrease in clinical and radiographic outcomes, by using as an inclusion criterion "a CRP level of >10 mg/liter and/or an MBDA score of >44." © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

An Ontology-based Architecture for Integration of Clinical Trials Management Applications

PubMed Central

Shankar, Ravi D.; Martins, Susana B.; O’Connor, Martin; Parrish, David B.; Das, Amar K.

2007-01-01

Management of complex clinical trials involves coordinated-use of a myriad of software applications by trial personnel. The applications typically use distinct knowledge representations and generate enormous amount of information during the course of a trial. It becomes vital that the applications exchange trial semantics in order for efficient management of the trials and subsequent analysis of clinical trial data. Existing model-based frameworks do not address the requirements of semantic integration of heterogeneous applications. We have built an ontology-based architecture to support interoperation of clinical trial software applications. Central to our approach is a suite of clinical trial ontologies, which we call Epoch, that define the vocabulary and semantics necessary to represent information on clinical trials. We are continuing to demonstrate and validate our approach with different clinical trials management applications and with growing number of clinical trials. PMID:18693919

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database.

PubMed

Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2017-01-01

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P <0.001) using non-randomized assignment (90.1% vs. 66.7%, P <0.001) than other oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P <0.001). These findings raise concerns that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials.

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database

PubMed Central

Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2017-01-01

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P <0.001) using non-randomized assignment (90.1% vs. 66.7%, P <0.001) than other oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P <0.001). These findings raise concerns that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials. PMID:28042342