Method Development for Clinical Comprehensive Evaluation of Pediatric Drugs Based on Multi-Criteria Decision Analysis: Application to Inhaled Corticosteroids for Children with Asthma.

PubMed

Yu, Yuncui; Jia, Lulu; Meng, Yao; Hu, Lihua; Liu, Yiwei; Nie, Xiaolu; Zhang, Meng; Zhang, Xuan; Han, Sheng; Peng, Xiaoxia; Wang, Xiaoling

2018-04-01

Establishing a comprehensive clinical evaluation system is critical in enacting national drug policy and promoting rational drug use. In China, the 'Clinical Comprehensive Evaluation System for Pediatric Drugs' (CCES-P) project, which aims to compare drugs based on clinical efficacy and cost effectiveness to help decision makers, was recently proposed; therefore, a systematic and objective method is required to guide the process. An evidence-based multi-criteria decision analysis model that involved an analytic hierarchy process (AHP) was developed, consisting of nine steps: (1) select the drugs to be reviewed; (2) establish the evaluation criterion system; (3) determine the criterion weight based on the AHP; (4) construct the evidence body for each drug under evaluation; (5) select comparative measures and calculate the original utility score; (6) place a common utility scale and calculate the standardized utility score; (7) calculate the comprehensive utility score; (8) rank the drugs; and (9) perform a sensitivity analysis. The model was applied to the evaluation of three different inhaled corticosteroids (ICSs) used for asthma management in children (a total of 16 drugs with different dosage forms and strengths or different manufacturers). By applying the drug analysis model, the 16 ICSs under review were successfully scored and evaluated. Budesonide suspension for inhalation (drug ID number: 7) ranked the highest, with comprehensive utility score of 80.23, followed by fluticasone propionate inhaled aerosol (drug ID number: 16), with a score of 79.59, and budesonide inhalation powder (drug ID number: 6), with a score of 78.98. In the sensitivity analysis, the ranking of the top five and lowest five drugs remains unchanged, suggesting this model is generally robust. An evidence-based drug evaluation model based on AHP was successfully developed. The model incorporates sufficient utility and flexibility for aiding the decision-making process, and can be a useful tool for the CCES-P.

Application of a policy framework for the public funding of drugs for rare diseases.

PubMed

Winquist, Eric; Coyle, Doug; Clarke, Joe T R; Evans, Gerald A; Seager, Christine; Chan, Winnie; Martin, Janet

2014-08-01

In many countries, decisions about the public funding of drugs are preferentially based on the results of randomized trials. For truly rare diseases, such trials are not typically available, and approaches by public payers are highly variable. In view of this, a policy framework intended to fairly evaluate these drugs was developed by the Drugs for Rare Diseases Working Group (DRDWG) at the request of the Ontario Public Drug Programs. To report the initial experience of applying a novel evaluation framework to funding applications for drugs for rare diseases. Retrospective observational cohort study. Clinical effectiveness, costs, funding recommendations, funding approval. Between March 2008 and February 2013, eight drugs were evaluated using the DRDWG framework. The estimated average annual drug cost per patient ranged from 28,000 to 1,200,000 Canadian dollars (CAD). For five drugs, full evaluations were completed, specific funding recommendations were made by the DRDWG, and funding was approved after risk-sharing agreements with the manufacturers were negotiated. For two drugs, the disease indications were determined to be ineligible for consideration. For one drug, there was insufficient natural history data for the disease to provide a basis for recommendation. For the five drugs fully evaluated, 32 patients met the predefined eligibility criteria for funding, and five were denied based on predefined exclusion criteria. The framework improved transparency and consistency for evaluation and public funding of drugs for rare diseases in Ontario. The evaluation process will continue to be iteratively refined as feedback on actual versus expected clinical and economic outcomes is incorporated.

21 CFR 807.35 - Notification of registrant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Research and Center for Drug Evaluation and Research, as appropriate. Blood products shall be listed with the Center for Biologics Evaluation and Research, Food and Drug Administration, pursuant to part 607 of this chapter; drug products shall be listed with the Center for Drug Evaluation and Research, Food...

21 CFR 807.35 - Notification of registrant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Research and Center for Drug Evaluation and Research, as appropriate. Blood products shall be listed with the Center for Biologics Evaluation and Research, Food and Drug Administration, pursuant to part 607 of this chapter; drug products shall be listed with the Center for Drug Evaluation and Research, Food...

[Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

PubMed

Li, Yuanyuan; Xie, Yanming

2011-10-01

The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

[Cost-effectiveness of new drugs impacts reimbursement decision making but room for improvement].

PubMed

Hoomans, Ties; van der Roer, Nicole; Severens, Johan L; Delwel, Gepke O

2010-01-01

For new drugs to be included in appendix 1B of the drug reimbursement system, they must have proven added therapeutic value, an acceptable budget impact, and be cost-effective. To validate the latter, pharmacoeconomic evaluations have become mandatory. These evaluations should adhere to guidelines for pharmacoeconomic research. Our study evaluates: 1) the extent to which the pharmacoeconomic evaluations adherence pharmacoeconomic guidelines; 2) which guidelines are decisive in evaluating the validation of cost-effectiveness of new drugs; and 3) the impact of pharmacoeconomics in the recommendations and final decision making on drug reimbursement. Retrospective, descriptive study. We examined all 1B requests for reimbursement submitted to the Dutch Health Care Insurance Board and the Medicinal Products Reimbursement Committee between 1 January 2005 and 30 September 2008, and on which recommendations on drug reimbursement have been published (n = 21). Data on adherence to guidelines, validation of cost-effectiveness, and recommendations and decision making on drug reimbursement were extracted from publicly available sources by two independent evaluators. Quantitatively and qualitatively descriptive analyses were carried out. Since pharmacoeconomic evaluations have become mandatory, these evaluations increasingly adhere to guidelines for pharmacoeconomic research. This was particularly true of the perspective chosen, the relevant treatment comparator and the incremental and total analyses of costs and effects of the drugs under comparison. However, cost-effectiveness of new drugs was often inadequately validated by incorrect indications for drug use, and incorrect forms of evaluation or periods of analysis. In addition, costs and effects were not always correctly analysed, nor and not enough insight was provided into the analysis model used. Partially on the basis of pharmacoeconomics, 12 new drugs are reimbursed and 9 not. Cost-effectiveness of new drugs and more valid pharmacoeconomic evaluations appear to play an ever more important role in reimbursement decision making and the pursuit of better and affordable health care.

75 FR 37295 - Change of Address; Abbreviated New Drug Applications; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

..., 2010. FOR FURTHER INFORMATION CONTACT: Martin Shimer, Center for Drug Evaluation and Research, Food and... Drugs (HFD-600), Center for Drug Evaluation and Research, Food and Drug Administration, Metro Park North... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 312 and 314...

Antineoplastic agents: comparing off-label uses among authoritative drug compendia.

PubMed

Thompson, D F; Keefe, C C

1993-07-01

Unlabeled indications for antineoplastic drugs listed in the American Hospital Formulary-Drug Information, United States Pharmacopeia Dispensing Information-Drug Information for the Health Care Professional (Volume 1), and the American Medical Association-Drug Evaluations were evaluated. Specifically, the total number of unlabeled and unique uses (ie, not listed in either of the other two compendia) of 35 antineoplastic drugs were compared. Using a nonparametric analysis of variance to evaluate the results, significant differences in both the average unlabeled indications per drug and unique unlabeled indications per drug were found among the resources checked. The implications of the study results on reimbursement by private insurance carriers of unlabeled antineoplastic drug use is discussed in this article.

78 FR 44573 - Guidance for Industry on Providing Submissions in Electronic Format-Postmarket Non-Expedited...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... should contact the Center for Drug Evaluation and Research (CDER) or Center for Biologics and Evaluation and Research (CBER) and resubmit their non-expedited ICSRs in a compatible electronic format. \\1\\ For... guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug...

77 FR 8885 - Draft Guidance for Industry on Biosimilars: Questions and Answers Regarding Implementation of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

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Validating Self-Reports of Illegal Drug Use to Evaluate National Drug Control Policy: A Reanalysis and Critique

ERIC Educational Resources Information Center

Magura, Stephen

2010-01-01

Illicit drug use remains at high levels in the U.S. The federal Office of National Drug Control Policy evaluates the outcomes of national drug demand reduction policies by assessing annual changes in drug use from several federally sponsored annual national surveys. Such survey methods, relying exclusively on drug use as self-reported on…

78 FR 68854 - Over-the-Counter Ophthalmic Drug Products-Emergency Use Eyewash Products; Rescheduling of Public...

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2013-11-15

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77 FR 59929 - Guidance for Industry on Acute Bacterial Exacerbations of Chronic Bronchitis in Patients With...

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2012-10-01

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78 FR 15956 - Guidance for Industry on Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation...

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2013-03-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0595... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug...

78 FR 78366 - Draft Guidance for Industry on Naming of Drug Products Containing Salt Drug Substances; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

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A protocol to evaluate drug-related workplace impairment.

PubMed

Reisfield, Gary M; Shults, Theodore; Demery, Jason; Dupont, Robert

2013-03-01

The dramatic increase in the use and abuse of prescription controlled substances, cannabis, and a rapidly evolving array of legal and illegal psychotropic drugs has led to a growing concern by employers about workplace impairment, incidents, and accidents. The Federal Workplace Drug Testing Programs, which serve as a template for most private sector programs, focus on a small group of illicit drugs, but disregard the wider spectrum of legal and illegal psychotropic drugs and prescription controlled substances. We propose a protocol for the evaluation of workplace impairment, based on comprehensive drug and alcohol testing at the time of suspected impairment, followed expeditiously by a comprehensive physician evaluation, including a focused medical history with an emphasis on controlled substance use, physical and mental status examinations, evaluation of employee adherence to prescription medication instructions, additional drug testing if indicated, use of collateral sources of information, and querying of state prescription monitoring databases. Finally, we propose suggestions for optimizing the evaluation of drug-related workplace impairment.

[Significance of re-evaluation and development of Chinese herbal drugs].

PubMed

Gao, Yue; Ma, Zengchun; Zhang, Boli

2012-01-01

The research of new herbal drugs involves in new herbal drugs development and renew the old drugs. It is necessary to research new herbal drugs based on the theory of traditional Chinese medicine (TCM). The current development of famous TCM focuses on the manufacture process, quality control standards, material basis and clinical research. But system management of security evaluation is deficient, the relevant system for the safety assessment TCM has not been established. The causes of security problems, security risks, target organ of toxicity, weak link of safety evaluation, and ideas of safety evaluation are discussed in this paper. The toxicology research of chinese herbal drugs is necessary based on standard of good laboratory practices (GLP), the characteristic of Chinese herbal drugs is necessary to be fully integrated into safety evaluation. The safety of new drug research is necessary to be integrated throughout the entire process. Famous Chinese medicine safety research must be paid more attention in the future.

76 FR 53909 - Draft Guidance for Industry on Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

... your comment on this draft guidance before it begins work on the final version of the guidance, submit... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm...

78 FR 8446 - Center for Drug Evaluation and Research; Prescription Drug Labeling Improvement and Enhancement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-06

... products. \\5\\ Ibid. \\6\\ See http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 201, 314, and 601 [Docket No. FDA-2013-N-0059] Center for Drug Evaluation and Research; Prescription Drug Labeling...

78 FR 15371 - Drug Development for Chronic Fatigue Syndrome and Myalgic Encephalomyelitis; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-11

... and Drug Administration (FDA), Center for Drug Evaluation and Research, is announcing a public..., patient advocates, patients, and clinicians on how to identify sound, quantitative outcome measures that.... Contact Persons: Mary Gross, Center for Drug Evaluation and Research, Food and Drug Administration, 10903...

78 FR 37551 - Request for Nominations for Voting and/or Nonvoting Consumer Representatives on Public Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-21

..., Center for Drug Anesthetic and Analgesic Evaluation and Research, Food and Drug Drugs. Administration... vacancies Approximate date needed Anesthetic and Analgesic Drugs-- 1--Voting Immediately. Knowledgeable in.... Anesthetic and Analgesic Drug Products The committee reviews and evaluates available data concerning the...

Modulated evaluation metrics for drug-based ontologies.

PubMed

Amith, Muhammad; Tao, Cui

2017-04-24

Research for ontology evaluation is scarce. If biomedical ontological datasets and knowledgebases are to be widely used, there needs to be quality control and evaluation for the content and structure of the ontology. This paper introduces how to effectively utilize a semiotic-inspired approach to ontology evaluation, specifically towards drug-related ontologies hosted on the National Center for Biomedical Ontology BioPortal. Using the semiotic-based evaluation framework for drug-based ontologies, we adjusted the quality metrics based on the semiotic features of drug ontologies. Then, we compared the quality scores before and after tailoring. The scores revealed a more precise measurement and a closer distribution compared to the before-tailoring. The results of this study reveal that a tailored semiotic evaluation produced a more meaningful and accurate assessment of drug-based ontologies, lending to the possible usefulness of semiotics in ontology evaluation.

Fluency of pharmaceutical drug names predicts perceived hazardousness, assumed side effects and willingness to buy.

PubMed

Dohle, Simone; Siegrist, Michael

2014-10-01

The impact of pharmaceutical drug names on people's evaluations and behavioural intentions is still uncertain. According to the representativeness heuristic, evaluations should be more positive for complex drug names; in contrast, fluency theory suggests that evaluations should be more positive for simple drug names. Results of three experimental studies showed that complex drug names were perceived as more hazardous than simple drug names and negatively influenced willingness to buy. The results are of particular importance given the fact that there is a worldwide trend to make more drugs available for self-medication. © The Author(s) 2013.

A regulatory perspective on the evaluation of hallucinogen drugs for human use.

PubMed

Calderon, Silvia N; Hunt, Joshua; Klein, Michael

2017-11-24

In recent years, there is renewed interest in the study of various hallucinogens for their potential therapeutic effects. In the United States of America (USA), the abuse potential assessment of a drug is carried out as part of the general safety and efficacy evaluation of a drug. Additionally, the abuse potential assessment is taken under consideration in determining if a drug needs to be subject to controls to minimize the abuse of the drug once on the market. This assessment is conducted for all new drugs with central nervous system (CNS) activity, that are chemically or pharmacologically similar to other drugs with known abuse potential, or drugs that produce psychoactive effects predictive of abuse, such as euphoria and hallucinations. This paper describes the regulatory framework for evaluating the abuse potential of new drugs, with emphasis on hallucinogens. The paper discusses the role of the United States Food and Drug Administration (FDA) in the evaluation of the abuse potential of drugs and its role in drug control, and provides an overview of the controlled status of hallucinogens and the requirements to conduct research with Schedule I substances in the USA. Published by Elsevier Ltd.

Experimental study and evaluation of radioprotective drugs

NASA Technical Reports Server (NTRS)

Smith, D. E.; Thomson, J. F.

1968-01-01

Experimental study evaluates radioprotective drugs administered before exposure either orally or intravenously. Specifically studied are the sources of radiation, choice of radiation dose, choice of animals, administration of drugs, the toxicity of protective agents and types of protective drug.

78 FR 27116 - Draft Guidance for Industry on Charging for Investigational Drugs Under an Investigational New...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD... Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852...: Colleen L. Locicero, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New...

76 FR 71349 - Dermatologic and Ophthalmic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

.... Contact Person: Yvette Waples, Center for Drug Evaluation and Research, Food and Drug Administration... following topics related to the use of ophthalmic drug products (products intended for use in the eye): (1... infection. FDA's Center for Drug Evaluation and Research would like the advisory committee to provide advice...

78 FR 44572 - Draft Guidance for Industry on Pre-Launch Activities Importation Requests; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0836...

75 FR 1060 - Draft Guidance for Industry on Planning for the Effects of High Absenteeism to Ensure...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-08

... Medically Necessary Drug Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., WO Bldg. 51, rm. 3359...

An evaluation of the completeness of drug-drug interaction-related information in package inserts.

PubMed

Ng, Giok Qin; Sklar, Grant Edward; Chng, Hui Ting

2017-02-01

The project aimed to evaluate the completeness of drug-drug interaction (DDI)-related information in package inserts (PIs) and develop a systematic approach to conduct the evaluation. DDI-related information in the branded PIs of statins, macrolides, protease inhibitors and selected drugs of narrow therapeutic index (DNTI) were evaluated against the criteria distilled from the Food and Drug Administration (FDA) labelling recommendation guidance document. Decision trees were crafted and employed in the evaluation process. Scores were computed to give each PI an overall completeness score and individual criterion completeness score. The Kruskal-Wallis test and Dunn's multiple comparison test were used to assess the differences in the completeness scores. The mean overall completeness score of the 21 PIs was 35.7 ± 13.4 % (range 12.2-62 %). Eight out of the 11 individual evaluation criterion had a mean completeness score below 50 %. A subclass analysis conducted revealed that PIs from the different drug classes differed in the type of DDI-related information, such that they are more complete or less complete. The completeness score of DDI-related information in the PIs varied extensively amongst and within drug classes. A consensus between the authorities and drug companies on the type and quality of DDI-related information to be included could improve their completeness in PIs and make PIs a valuable source of DDI reference. Decision trees, albeit not validated yet, lay the groundwork for a valuable tool to evaluate DDI-related or other drug information.

The evaluation of the abuse liability of drugs.

PubMed

Johanson, C E

1990-01-01

In order to place appropriate restrictions upon the availability of certain therapeutic agents to limit their abuse, it is important to assess abuse liability, an important aspect of drug safety evaluation. However, the negative consequences of restriction must also be considered. Drugs most likely to be tested are psychoactive compounds with therapeutic indications similar to known drugs of abuse. Methods include assays of pharmacological profile, drug discrimination procedures, self-administration procedures, and measures of drug-induced toxicity including evaluations of tolerance and physical dependence. Furthermore, the evaluation of toxicity using behavioural end-points is an important component of the assessment, and it is generally believed that the most valid procedure in this evaluation is the measurement of drug self-administration. However, even this method rarely predicts the extent of abuse of a specific drug. Although methods are available which appear to measure relative abuse liability, these procedures are not validated for all drug classes. Thus, additional strategies, including abuse liability studies in humans, modelled after those used with animals, must be used in order to make a more informed prediction. Although there is pressure to place restrictions on new drugs at the time of marketing, in light of the difficulty of predicting relative abuse potential, a better strategy might be to market a drug without restrictions, but require postmarketing surveillance in order to obtain more accurate information on which to base a final decision.

Evaluation of drug reviews.

PubMed

Hendrickson, N M; Amerson, A B

1986-10-01

Drug reviews appearing in Clinical Pharmacy, Drug Intelligence and Clinical Pharmacy (DICP), Drugs, and Pharmacotherapy from January 1982 through December 1984 were evaluated for number, duplication among journals, timeliness, scope, and format. The design of this study was primarily quantitative rather than qualitative. Pharmacotherapy published the most reviews (49), followed by Drugs (43), Clinical Pharmacy (37), and DICP (29). Drugs and Pharmacotherapy published the largest number of unique reviews (agents not reviewed by the other journals during the study period), while Pharmacotherapy and Clinical Pharmacy published the most reviews on newly marketed drugs. Reviews of four drugs (acyclovir, moxalactam, ranitidine, and trazodone) were compared in terms of major sections, terminology and format, bibliography, use of tables and figures, scope of evaluative comments, and review process. Reviews in Drugs consistently contained the most references and tables and provided the most detail. Information was most accessible in Drugs, followed by Pharmacotherapy. Drugs used the largest panel of reviewers. All of the journals provided evaluative comments, although the scope varied. Continuing-education credit is available for review articles in Clinical Pharmacy and DICP. In selecting one or more of these journals, individuals or institutions should compare their needs with regard to the timeliness, scope, and format of the review articles in each journal.

Consensus Recommendations for Systematic Evaluation of Drug-Drug Interaction Evidence for Clinical Decision Support

PubMed Central

Scheife, Richard T.; Hines, Lisa E.; Boyce, Richard D.; Chung, Sophie P.; Momper, Jeremiah; Sommer, Christine D.; Abernethy, Darrell R.; Horn, John; Sklar, Stephen J.; Wong, Samantha K.; Jones, Gretchen; Brown, Mary; Grizzle, Amy J.; Comes, Susan; Wilkins, Tricia Lee; Borst, Clarissa; Wittie, Michael A.; Rich, Alissa; Malone, Daniel C.

2015-01-01

Background Healthcare organizations, compendia, and drug knowledgebase vendors use varying methods to evaluate and synthesize evidence on drug-drug interactions (DDIs). This situation has a negative effect on electronic prescribing and medication information systems that warn clinicians of potentially harmful medication combinations. Objective To provide recommendations for systematic evaluation of evidence from the scientific literature, drug product labeling, and regulatory documents with respect to DDIs for clinical decision support. Methods A conference series was conducted to develop a structured process to improve the quality of DDI alerting systems. Three expert workgroups were assembled to address the goals of the conference. The Evidence Workgroup consisted of 15 individuals with expertise in pharmacology, drug information, biomedical informatics, and clinical decision support. Workgroup members met via webinar from January 2013 to February 2014. Two in-person meetings were conducted in May and September 2013 to reach consensus on recommendations. Results We developed expert-consensus answers to three key questions: 1) What is the best approach to evaluate DDI evidence?; 2) What evidence is required for a DDI to be applicable to an entire class of drugs?; and 3) How should a structured evaluation process be vetted and validated? Conclusion Evidence-based decision support for DDIs requires consistent application of transparent and systematic methods to evaluate the evidence. Drug information systems that implement these recommendations should be able to provide higher quality information about DDIs in drug compendia and clinical decision support tools. PMID:25556085

Evaluation of the Triage TOX Drug Screen Assay for Detection of 11 Drugs of Abuse and Therapeutic Drugs.

PubMed

Bang, Hae In; Jang, Mi Ae; Lee, Yong Wha

2017-11-01

The demand for rapid and broad clinical toxicology screens is on the rise. Recently, a new rapid toxicology screening test, the Triage TOX Drug Screen (Alere Inc., USA), which can simultaneously detect 11 drugs of abuse and therapeutic drugs with an instrument-read cartridge, was developed. In the present study, we evaluated the efficacy of this new on-site immunoassay using 105 urine specimens; the results were compared with those obtained by using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-TMS). Precision was evaluated according to the CLSI EP12-A2 for analyte concentrations near the cutoff, including C₅₀ and±30% of C₅₀, for each drug using standard materials. The C₅₀ specimens yielded 35-65% positive results and the±30% concentration range of all evaluated drugs encompassed the C₅-C₉₅ interval. The overall percent agreement of the Triage TOX Drug Screen was 92.4-100% compared with UPLC-TMS; however, the Triage TOX Drug Screen results showed some discordant cases including acetaminophen, amphetamine, benzodiazepine, opiates, and tricyclic antidepressants. The overall performance of the Triage TOX Drug Screen assay was comparable to that of UPLC-TMS for screening of drug intoxication in hospitals. This assay could constitute a useful screening method for drugs of abuse and therapeutic drugs in urine. © The Korean Society for Laboratory Medicine.

75 FR 59935 - Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

... safety reporting for human drug products: Janet Norden, Center for Drug Evaluation and Research, Food and... for Biologics Evaluation and Research, Food and Drug Administration,1401 Rockville Pike, suite 200N..., 2003. At the request of industry, and to provide all interested persons additional time to comment, the...

76 FR 1170 - Draft Guidance for Industry on Postmarketing Adverse Event Reporting for Medical Products and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

... copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research..., Silver Spring, MD 20993- 0002, 301-796-8510. Regarding human drug products: Solomon Iyasu, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm...

Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

PubMed Central

Lee, Hsin-chung; Ling, Qing-Dong; Yu, Wan-Chun; Hung, Chunh-Ming; Kao, Ta-Chun; Huang, Yi-Wei; Higuchi, Akon

2013-01-01

Purpose We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs). Methods The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction. Results Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells. Conclusion Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments. PMID:23818760

Development and evaluation of an algorithm to facilitate drug prescription for inpatients with feeding tubes.

PubMed

Lohmann, Kristina; Freigofas, Julia; Leichsenring, Julian; Wallenwein, Chantal Marie; Haefeli, Walter Emil; Seidling, Hanna Marita

2015-04-01

We aimed to develop and evaluate an algorithm to facilitate drug switching between primary and tertiary care for patients with feeding tubes. An expert consortium developed an algorithm and applied it manually to 267 preadmission drugs of 46 patients admitted to a surgical ward of a tertiary care university hospital between June 12 and December 2, 2013, and requiring a feeding tube during their inpatient stay. The new algorithm considered the following principles: Drugs should be ideally listed on the hospital drug formulary (HDF). Additionally, drugs should include the same ingredient instead of a therapeutic equivalent. Preferred dosage forms were appropriate liquids, followed by solid drugs with liquid administration form, and solid drugs that could be crushed and/or suspended. Of all evaluated drugs, 83.5% could be switched to suitable drugs listed on the HDF and another 6.0% to drugs available on the German drug market. Additionally, for 4.1% of the drugs, the integration of individual switching rules allowed the switch from enteric-coated to immediate-release drugs. Consequently, 6.4% of the drugs could not be automatically switched and required case-to-case decision by a clinical professional (e.g., from sustained-release to immediate-release). The predefined principles were successfully integrated in the new algorithm. Thus, the algorithm switched more than 90% of the evaluated preadmission drugs to suitable drugs for inpatients with feeding tubes. This finding suggests that the algorithm can readily be transferred to an electronic format and integrated into a clinical decision support system.

21 CFR 7.41 - Health hazard evaluation and recall classification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Health hazard evaluation and recall classification. 7.41 Section 7.41 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., and Industry Responsibilities § 7.41 Health hazard evaluation and recall classification. (a) An...

Delegations of authority and organization; Center for Biologics Evaluation and Research, Center for Devices and Radiological Health, and Center for Drug Evaluation and Research--FDA. Final rule.

PubMed

1991-11-21

The Food and Drug Administration (FDA) is amending the regulations for delegations of authority relating to premarket approval of products that are or contain a biologic, a device, or a drug. The amendment grants directors, deputy directors, and certain other supervisory personnel in the Center for Biologics Evaluation and Research (CBER), the Center for Devices and Radiological Health (CDRH), and the Center for Drug Evaluation and Research (CDER) reciprocal premarket approval authority to approve such products.

21 CFR 203.37 - Investigation and notification requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New... Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Investigation and notification requirements. 203...

21 CFR 601.9 - Licenses; reissuance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Licenses; reissuance. 601.9 Section 601.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research. (b...

21 CFR 601.9 - Licenses; reissuance.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Licenses; reissuance. 601.9 Section 601.9 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research. (b...

Drug Education: Limited Progress in Program Evaluation. Testimony before the Subcommittee on Select Education and Civil Rights, Committee on Education and Labor, House of Representatives.

ERIC Educational Resources Information Center

Chelimsky, Eleanor

This testimony reports on the state of program evaluation in the field of drug education for youth. The report focuses on the role of evaluation in: (1) the Department of Education's program of grants to states and local school districts under the Drug-Free Schools and Communities Act (DFSCA) of 1986, as amended; (2) the department's Drug-Free…

Rational drug use--evaluation of a training programme for interns.

PubMed

Natu, M V; Zachariah, P; Zachariah, A; Chand, S; Singh, T; Choudhry, K

1995-09-01

A workshop covering various aspects of rational drug use was conducted for interns of Christian Medical College, Ludhiana. Evaluation of the workshop revealed that it was able to bring about an attitudinal change regarding rational drug use. The methodology and evaluation procedures have been described. It is suggested that similar attempts should be made at all medical colleges so that every graduate enters medical practice with a positive attitude towards rational drug use.

21 CFR 314.440 - Addresses for applications and abbreviated applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-600), Center for Drug Evaluation and Research, Food and Drug Administration, Metro Park North II, 7500... Evaluation and Research, Food and Drug Administration, Attn: [insert name of person], Metro Park North II... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Addresses for applications and abbreviated...

21 CFR 203.70 - Application for a reward.

Code of Federal Regulations, 2010 CFR

2010-04-01

... for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver... Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Application for a reward. 203.70 Section 203.70...

21 CFR 202.1 - Prescription-drug advertisements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... scientific training and experience to evaluate the safety and effectiveness of such drugs; or (b) For which... evaluate the safety and effectiveness of the drug involved, on the basis of which it can fairly and... descriptive of a drug and references published (for example, the “Physicians Desk Reference”) for use by...

21 CFR 202.1 - Prescription-drug advertisements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... scientific training and experience to evaluate the safety and effectiveness of such drugs; or (b) For which... evaluate the safety and effectiveness of the drug involved, on the basis of which it can fairly and... descriptive of a drug and references published (for example, the “Physicians Desk Reference”) for use by...

21 CFR 202.1 - Prescription-drug advertisements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... scientific training and experience to evaluate the safety and effectiveness of such drugs; or (b) For which... evaluate the safety and effectiveness of the drug involved, on the basis of which it can fairly and... descriptive of a drug and references published (for example, the “Physicians Desk Reference”) for use by...

21 CFR 202.1 - Prescription-drug advertisements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... scientific training and experience to evaluate the safety and effectiveness of such drugs; or (b) For which... evaluate the safety and effectiveness of the drug involved, on the basis of which it can fairly and... descriptive of a drug and references published (for example, the “Physicians Desk Reference”) for use by...

21 CFR 202.1 - Prescription-drug advertisements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... scientific training and experience to evaluate the safety and effectiveness of such drugs; or (b) For which... evaluate the safety and effectiveness of the drug involved, on the basis of which it can fairly and... descriptive of a drug and references published (for example, the “Physicians Desk Reference”) for use by...

Drug Education: Goals, Approaches, Evaluation, ERS Report.

ERIC Educational Resources Information Center

Bushey, Julia A.

An examination of the extensive drug education literature as well as of specific school drug education programs indicates that the present confusion over drug education results from confusion over definitions, goals, approaches, and evaluation. This report, based on an examination of recent literature and on information and printed materials on…

21 CFR 203.12 - An appeal from an adverse decision by the district office.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to the Office of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration... and Biologics Quality (HFM-600), Center for Biologics Evaluation and Research, Food and Drug... and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002...

78 FR 52932 - Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Institutional...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-27

... guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug... Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852...-regulated products in determining that the proposed research satisfies the criteria for approval contained...

21 CFR 203.12 - An appeal from an adverse decision by the district office.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to the Office of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration... and Biologics Quality (HFM-600), Center for Biologics Evaluation and Research, Food and Drug... and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002...

21 CFR 807.90 - Format of a premarket notification submission.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville... to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug Administration... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Format of a premarket notification submission. 807...

In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions.

PubMed

Bani-Jaber, Ahmad; Alshawabkeh, Iyad; Abdullah, Samaa; Hamdan, Imad; Ardakani, Adel; Habash, Maha

2017-07-01

Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug-protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Drug dissolution from the dispersions was evaluated in simulated intestinal fluid as enzyme free and trypsin-enriched media. Furthermore, in vivo drug absorption of MA from CS-MA coprecipitate was evaluated in rats, in comparison with a reference SD of polyethylene glycol and MA (PEG-MA SD). Relative to other CS preparations, CS-MA coprecipitate showed the highest loss of drug crystallinity, drug micronization, and CS-MA interaction. CS remarkably enhanced the dissolution rate and extent of MA from the physical and kneaded mixtures. However, the highest dissolution enhancement was obtained when MA was coprecipitated with CS. Trypsin that can hydrolyze CS during dissolution resulted in further enhancement of MA dissolution from the physical and kneaded mixtures. However, a corresponding retardation effect was obtained for the coprecipitate. In correlation with in vitro drug release, CS-MA coprecipitate also showed significantly higher MA bioavailability in rats than PEG-MA SD.

Evaluation of consumer drug information databases.

PubMed

Choi, J A; Sullivan, J; Pankaskie, M; Brufsky, J

1999-01-01

To evaluate prescription drug information contained in six consumer drug information databases available on CD-ROM, and to make health care professionals aware of the information provided, so that they may appropriately recommend these databases for use by their patients. Observational study of six consumer drug information databases: The Corner Drug Store, Home Medical Advisor, Mayo Clinic Family Pharmacist, Medical Drug Reference, Mosby's Medical Encyclopedia, and PharmAssist. Not applicable. Not applicable. Information on 20 frequently prescribed drugs was evaluated in each database. The databases were ranked using a point-scale system based on primary and secondary assessment criteria. For the primary assessment, 20 categories of information based on those included in the 1998 edition of the USP DI Volume II, Advice for the Patient: Drug Information in Lay Language were evaluated for each of the 20 drugs, and each database could earn up to 400 points (for example, 1 point was awarded if the database mentioned a drug's mechanism of action). For the secondary assessment, the inclusion of 8 additional features that could enhance the utility of the databases was evaluated (for example, 1 point was awarded if the database contained a picture of the drug), and each database could earn up to 8 points. The results of the primary and secondary assessments, listed in order of highest to lowest number of points earned, are as follows: Primary assessment--Mayo Clinic Family Pharmacist (379), Medical Drug Reference (251), PharmAssist (176), Home Medical Advisor (113.5), The Corner Drug Store (98), and Mosby's Medical Encyclopedia (18.5); secondary assessment--The Mayo Clinic Family Pharmacist (8), The Corner Drug Store (5), Mosby's Medical Encyclopedia (5), Home Medical Advisor (4), Medical Drug Reference (4), and PharmAssist (3). The Mayo Clinic Family Pharmacist was the most accurate and complete source of prescription drug information based on the USP DI Volume II and would be an appropriate database for health care professionals to recommend to patients.

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...

75 FR 54343 - Center for Biologics Evaluation and Research eSubmitter Pilot Evaluation Program for Blood...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0436... That Collect Whole Blood and Blood Components AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (CBER) is...

76 FR 71045 - Center for Biologics Evaluation and Research Report of Scientific and Medical Literature and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... and Development (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and Drug... CONTACT: Paul E. Levine, Jr., Center for Biologics Evaluation and Research (HFM-17), Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0599...

An Evaluation of Immediate Outcomes and Fidelity of a Drug Abuse Prevention Program in Continuation High Schools: Project towards No Drug Abuse (TND)

ERIC Educational Resources Information Center

Lisha, Nadra E.; Sun, Ping; Rohrbach, Louise A.; Spruijt-Metz, Donna; Unger, Jennifer B.; Sussman, Steve

2012-01-01

The present study provides an implementation fidelity, process, and immediate outcomes evaluation of Project Towards No Drug Abuse (TND), a drug prevention program targeting continuation high school youth (n = 1426) at risk for drug abuse. A total of 24 schools participated in three randomized conditions: TND Only, TND and motivational…

76 FR 12847 - Change of Address; Requests for Exemption From the Bar Code Label Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

... INFORMATION CONTACT: Rikin Mehta, Center for Drug Evaluation and Research, Food and Drug Administration, 10903... and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Silver Spring, MD... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Silver Spring, MD...

78 FR 7784 - Draft Guidance for Industry on Enrichment Strategies for Clinical Trials To Support Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-04

... FURTHER INFORMATION CONTACT: Robert Temple, Center for Drug Evaluation and Research, Food and Drug... Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1145...

77 FR 69634 - Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0784] Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals... Effectiveness of Anticoccidial Drugs in Food-Producing Animals.'' The guidance provides guidance to industry for...

76 FR 72422 - Draft Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0784] Draft Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

77 FR 10536 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, Silver..., Center for Drug Evaluation and Research (HFD-600), Food and Drug Administration, 7519 Standish Pl... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369...

21 CFR 570.20 - General principles for evaluating the safety of food additives.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false General principles for evaluating the safety of food additives. 570.20 Section 570.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES Food Additive...

A Drug Interactions Elective Course

PubMed Central

2009-01-01

Objectives To evaluate the impact of a drug interactions elective course on student knowledge and skills. Design A drug interactions elective which focused on assessment and application of drug interaction information and identification and management of commonly encountered drug interactions by therapeutic category was offered to third-year PharmD students. Students were expected to (1) determine whether a given interaction was clinically significant or required pharmacist intervention, and (2) make rational, scientifically sound, practical recommendations for management of drug interactions. Evaluation and Assessment Assessment included course evaluations, student self-assessments, and knowledge and skills assessments. Students who completed the course were more confident in their abilities relating to drug interactions than students who did not complete the course. Students who completed the course scored significantly better in all areas of the assessment compared to students who did not complete the course. Course evaluation results were also positive. Conclusion A course devoted to the identification and management of drug interactions improved PharmD students' knowledge and skills and could potentially improve the patient care they provide in the future. PMID:19657505

Reporting of meta-analyses of randomized controlled trials with a focus on drug safety: an empirical assessment.

PubMed

Hammad, Tarek A; Neyarapally, George A; Pinheiro, Simone P; Iyasu, Solomon; Rochester, George; Dal Pan, Gerald

2013-01-01

Due to the sparse nature of serious drug-related adverse events (AEs), meta-analyses combining data from several randomized controlled trials (RCTs) to evaluate drug safety issues are increasingly being conducted and published, influencing clinical and regulatory decision making. Evaluation of meta-analyses involves the assessment of both the individual constituent trials and the approaches used to combine them. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting framework is designed to enhance the reporting of systematic reviews and meta-analyses. However, PRISMA may not cover all critical elements useful in the evaluation of meta-analyses with a focus on drug safety particularly in the regulatory-public health setting. This work was conducted to (1) evaluate the adherence of a sample of published drug safety-focused meta-analyses to the PRISMA reporting framework, (2) identify gaps in this framework based on key aspects pertinent to drug safety, and (3) stimulate the development and validation of a more comprehensive reporting tool that incorporates elements unique to drug safety evaluation. We selected a sample of meta-analyses of RCTs based on review of abstracts from high-impact journals as well as top medical specialty journals between 2009 and 2011. We developed a preliminary reporting framework based on PRISMA with specific additional reporting elements critical for the evaluation of drug safety meta-analyses of RCTs. The reporting of pertinent elements in each meta-analysis was reviewed independently by two authors; discrepancies in the independent evaluations were resolved through discussions between the two authors. A total of 27 meta-analyses, 12 from highest impact journals, 13 from specialty medical journals, and 2 from Cochrane reviews, were identified and evaluated. The great majority (>85%) of PRISMA elements were addressed in more than half of the meta-analyses reviewed. However, the majority of meta-analyses (>60%) did not address most (>80%) of the additional reporting elements critical for the evaluation of drug safety. Some of these elements were not addressed in any of the reviewed meta-analyses. This review included a sample of meta-analyses, with a focus on drug safety, recently published in high-impact journals; therefore, we may have underestimated the extent of the reporting problem across all meta-analyses of drug safety. Furthermore, temporal trends in reporting could not be evaluated in this review because of the short time interval selected. While the majority of PRISMA elements were addressed by most studies reviewed, the majority of studies did not address most of the additional safety-related elements. These findings highlight the need for the development and validation of a drug safety reporting framework and the importance of the current initiative by the Council for International Organizations of Medical Sciences (CIOMS) to create a guidance document for drug safety information synthesis/meta-analysis, which may improve reporting, conduct, and evaluation of meta-analyses of drug safety and inform clinical and regulatory decision making.

Evaluation of a primary school drug drama project: methodological issues and key findings.

PubMed

Starkey, F; Orme, J

2001-10-01

This paper describes the impact evaluation of a primary school drug drama project developed by a health promotion service and a theatre's education department in England. The project targeted 10-11 year olds in 41 schools with an interactive drama production and workshop day on attitudes, choices, decisions and risks of alcohol, tobacco and illegal drug use. Parents were also involved in parents' evenings and watching children's performances. The research consisted of both process evaluation, consultation with pupils, teachers, parents, actors and health promotion staff on the project itself, and impact evaluation which looked at potential changes in children's knowledge, attitudes and decision-making skills. This paper reports findings of the impact evaluation, from six of the schools participating in the project. The impact evaluation consisted of pre- and post-project testing using a 'draw and write' and a problem-solving exercise. These findings suggest that the project had a significant impact on the children's knowledge of names of specific illegal drugs, and on their awareness that alcohol and cigarettes were also drugs, and secondly encouraged the children to think in less stereotypical terms about drugs and drug users. The problem-solving exercise, involving decision-making scenarios, showed small but positive trends between pre- and post-project solutions in more than half of the response categories. Methodological difficulties relating to evaluating such a project are discussed.

[HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

PubMed

Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

2017-04-01

In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands on quality and transparency, triggered by, amongst others, current legislation (Hospital Structures Act, anti-corruption legislation). Copyright © 2017. Published by Elsevier GmbH.

[Process and key points of clinical literature evaluation of post-marketing traditional Chinese medicine].

PubMed

Liu, Huan; Xie, Yanming

2011-10-01

The clinical literature evaluation of the post-marketing traditional Chinese medicine is a comprehensive evaluation by the comprehensive gain, analysis of the drug, literature of drug efficacy, safety, economy, based on the literature evidence and is part of the evaluation of evidence-based medicine. The literature evaluation in the post-marketing Chinese medicine clinical evaluation is in the foundation and the key position. Through the literature evaluation, it can fully grasp the information, grasp listed drug variety of traditional Chinese medicines second development orientation, make clear further clinical indications, perfect the medicines, etc. This paper discusses the main steps and emphasis of the clinical literature evaluation. Emphasizing security literature evaluation should attach importance to the security of a comprehensive collection drug information. Safety assessment should notice traditional Chinese medicine validity evaluation in improving syndrome, improveing the living quality of patients with special advantage. The economics literature evaluation should pay attention to reliability, sensitivity and practicability of the conclusion.

78 FR 2676 - Draft Guidance for Industry on Abuse-Deterrent Opioids-Evaluation and Labeling; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-14

... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver... Evaluation and Research (HFD-170), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 3160... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0045...

Evaluation of certain veterinary drug residues in food. Seventy-eighth report of the Joint FAO/WHO Expert Committee on Food Additives.

PubMed

2014-01-01

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues of food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including extrapolation of maximum residue limits (MRLs) to minor species, MRLs for veterinary drug residues in honey, MRLs relating to fish and fish species, dietary exposure assessment methodologies, the decision-tree approach to the evaluation of residues of veterinary drugs and guidance for JECFA experts. Summaries follow of the Committee's evaluations of toxicology and residue data on a variety of veterinary drugs: two anthelminthic agents (derquantel, monepantel), three antiparasitic agents (emanectin benzoate, ivermectin, lasalocid sodium), one antibacterial, antifungal and anthelminthic agent (gentian violet), a production aid (recombinant bovine somatotropins) and an adrenoceptor agonist and growth promoter (zilpaterol hydorchloride). Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs)) and proposed MRLs.

Evaluation of drug interaction microcomputer software: Dambro's Drug Interactions.

PubMed

Poirier, T I; Giudici, R A

1990-01-01

Dambro's Drug Interactions was evaluated using general and specific criteria. The installation process, ease of learning and use were rated excellent. The user documentation and quality of the technical support were good. The scope of coverage, clinical documentation, frequency of updates, and overall clinical performance were fair. The primary advantages of the program are the quick searching and detection of drug interactions, and the attempt to provide useful interaction data, i.e., significance and reference. The disadvantages are the lack of current drug interaction information, outdated references, lack of evaluative drug interaction information, and the inability to save or print patient profiles. The program is not a good value for the pharmacist but has limited use as a quick screening tool.

78 FR 22552 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

... Evaluation Program (MPEP) for Mycobacterium tuberculosis and Nontuberculous Mycobacteria Drug Susceptibility... tuberculosis (TB), prevention of multi- drug resistance, and surveillance programs, CDC is requesting approval... Performance Evaluation Program for Mycobacterium tuberculosis and Non-tuberculous Mycobacterium Drug...

[The place of a new drug in the therapeutic strategy].

PubMed

Castaigne, A; Goehrs, J M; Ravoire, S

A therapeutic strategy is a hierarchical set of appropriate measures to provide an answer to a pathological state. A drug is a part of this set (together with the diagnosis, the environment and the other medicinal interventions or not). A new drug's place in a therapeutic strategy can be evaluated according to one or several referential(s) when it (or they) exist, referentials which express the state of knowledge before launch of the new drug. The drug's profile (indication or contraindication, etc.), at the point when the marketing authorization is given, is purely theoretical. One must evaluate the real place of the drug under its real conditions of use (pragmatic trials, observable surveys). A new drugs' place in a therapeutic strategy can only be evaluated in the course of time unless a therapeutic revolution occurs.

A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

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

Li, Xiaoguang; Department of Medical Microbiology, Harbin Medical University, Harbin 150086; Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811

Highlights: Black-Right-Pointing-Pointer We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. Black-Right-Pointing-Pointer The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. Black-Right-Pointing-Pointer In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviralmore » activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1{sub IIIB} and HIV-1{sub BaL} as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1{sub IIIB} activity, whereas fusion inhibitors showed both anti-HIV-1{sub IIIB} and anti-HIV-1{sub BaL} activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, 'phenotypic drug evaluation', may be applicable for the evaluation of various antiviral drugs in vivo.« less

Independent Evaluation of Middle School-Based Drug Prevention Curricula: A Systematic Review.

PubMed

Flynn, Anna B; Falco, Mathea; Hocini, Sophia

2015-11-01

Lack of robust program evaluation has hindered the effectiveness of school-based drug abuse prevention curricula overall. Independently evaluated randomized controlled trials (RCTs) of universal, middle school-based drug abuse prevention curricula are the most useful indicators of whether such programs are effective or ineffective. To conduct a systematic review identifying independently evaluated RCTs of universal, middle school-based drug abuse prevention curricula; extract data on study quality and substance use outcomes; and assess evidence of program effectiveness. PsycInfo, Educational Resources Information Center, Science Citation Index, Social Science Citation Index, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched between January 1, 1984, and March 15, 2015. Search terms included variations of drug, alcohol, tobacco, and marijuana use, as well as school, prevention, and effectiveness. Studies included in the review were RCTs carried out by independent evaluators of universal school-based drug prevention curricula available for dissemination in the United States that reported alcohol, tobacco, marijuana, or other drug use outcomes. Two researchers extracted data on study quality and outcomes independently using a data extraction form and met to resolve disagreements. A total of 5071 publications were reviewed, with 13 articles meeting final inclusion criteria. Of the 13 articles, 6 RCTs of 4 distinct school-based curricula were identified for inclusion. Outcomes were reported for 42 single-drug measures in the independent RCTs, with just 3 presenting statistically significant (P < .05) differences between the intervention group and the control group. One program revealed statistically significant positive effects at final follow-up (Lions-Quest Skills for Adolescence). The results of our review demonstrate the dearth of independent research that appropriately evaluates the effectiveness of universal, middle school-based drug prevention curricula. Independent evaluations show little evidence of effectiveness for widely used programs. New methods may be necessary to approach school-based adolescent drug prevention.

Application of Model Animals in the Study of Drug Toxicology

NASA Astrophysics Data System (ADS)

Song, Yagang; Miao, Mingsan

2018-01-01

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

Marathon Group Therapy with Former Drug Users.

ERIC Educational Resources Information Center

Page, Richard C.; Mannion, John

1980-01-01

Discusses the effects of marathon group therapy on attitudes of former drug users in a residential drug treatment center. Experimental group members responded higher on the group counseling evaluative subscale and lower on the guilt evaluative subscale than control members. (Author)

21 CFR 600.2 - Mailing addresses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (HFM-99), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville... biological products regulated by the Center for Drug Evaluation and Research (CDER). Unless otherwise stated... Research, Food and Drug Administration, 12229 Wilkins Ave., Rockville, MD 20852. Examples of such...

21 CFR 600.2 - Mailing addresses.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (HFM-99), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville... biological products regulated by the Center for Drug Evaluation and Research (CDER). Unless otherwise stated... Research, Food and Drug Administration, 12229 Wilkins Ave., Rockville, MD 20852. Examples of such...

Evaluating Intra-Articular Drug Delivery for the Treatment of Osteoarthritis in a Rat Model

PubMed Central

Allen, Kyle D.; Adams, Samuel B.

2010-01-01

Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may provide for the development of more successful OA treatment outcomes that have potential to reduce local joint inflammation, reduce joint destruction, offer pain relief, and restore patient activity levels and joint function. As increasing interest turns toward intra-articular drug delivery routes, parallel interest has emerged in evaluating drug biodistribution, safety, and efficacy in preclinical models. Rodent models provide major advantages for the development of drug delivery strategies, chiefly because of lower cost, successful replication of human OA-like characteristics, rapid disease development, and small joint volumes that enable use of lower total drug amounts during protocol development. These models, however, also offer the potential to investigate the therapeutic effects of local drug therapy on animal behavior, including pain sensitivity thresholds and locomotion characteristics. Herein, we describe a translational paradigm for the evaluation of an intra-articular drug delivery strategy in a rat OA model. This model, a rat interleukin-1β overexpression model, offers the ability to evaluate anti-interleukin-1 therapeutics for drug biodistribution, activity, and safety as well as the therapeutic relief of disease symptoms. Once the action against interleukin-1 is confirmed in vivo, the newly developed anti-inflammatory drug can be evaluated for evidence of disease-modifying effects in more complex preclinical models. PMID:19943805

Evaluation of a procedure to assess the adverse effects of illicit drugs.

PubMed

van Amsterdam, J G C; Best, W; Opperhuizen, A; de Wolff, F A

2004-02-01

The assessment procedure of new synthetic illicit drugs that are not documented in the UN treaty on psychotropic drugs was evaluated using a modified Electre model. Drugs were evaluated by an expert panel via the open Delphi approach, where the written score was discussed on 16 items, covering medical, health, legal, and criminalistic issues of the drugs. After this face-to-face discussion the drugs were scored again. Taking the assessment of ketamine as an example, it appeared that each expert used its own scale to score, and that policymakers do not score deviant from experts trained in the medical-biological field. Of the five drugs evaluated by the panel, p-methoxy-metamphetamine (PMMA), gamma-hydroxybutyric acid (GHB), and 4-methylthio-amphetamine (MTA) were assessed as more adverse than ketamine and psilocine and psilocybine-containing mushrooms. Whereas some experts slightly adjusted during the assessment procedure their opinion on ketamine and PMMA, the opinion on mushrooms was not affected by the discussion held between the two scoring rounds. All experts rank the five drugs in a similar way on the adverse effect scale i.e., concordance scale of the Electre model, indicating unanimity in the expert panel with respect to the risk classification of these abused drugs.

Evaluating a restrictive formulary system by assessing nonformulary-drug requests.

PubMed

Green, J A; Chawla, A K; Fong, P A

1985-07-01

Nonformulary-drug requests were used to evaluate a restrictive formulary system in a large university hospital, and a telephone survey of eight similar hospitals was conducted to assess the restrictiveness of their formulary systems. Nonformulary-drug requests were evaluated by two drug information pharmacists over a 12-month period (January-December 1984) to assess the frequency with which nonformulary items were ordered, the costs associated with the procurement of nonformulary drug products, and the rationales given by physicians when ordering nonformulary products. Of all nonformulary requests, 65% were for drugs previously evaluated by the pharmacy and therapeutics committee and denied admission to the formulary. A cost savings of $1887 would have resulted if formulary alternates had been used instead of nonformulary products. Excluding 22% of nonformulary items that were requested for the continuation of preadmission drug therapy, only 13% of the rationales for the remaining requests were appropriate. Although the eight other hospitals surveyed said they had restrictive formularies, all had frequent requests and procedures for procuring nonformulary items and some formularies included most available drugs. The formulary system at the study hospital was considered restrictive, but procedures for nonformulary-drug requests limited the effectiveness of the system. If any benefit is to result from formulary systems, hospitals must strengthen their enforcement of formulary restrictions.

Methodological quality of economic evaluations of new pharmaceuticals in The Netherlands.

PubMed

Hoomans, Ties; Severens, Johan L; van der Roer, Nicole; Delwel, Gepke O

2012-03-01

In the Netherlands, decisions about the reimbursement of new pharmaceuticals are based on cost effectiveness, as well as therapeutic value and budget impact. Since 1 January 2005, drug manufacturers are formally required to substantiate the cost effectiveness of drugs that have therapeutic added value in comparison with existing ones through pharmacoeconomic evaluations. Dutch guidelines for pharmacoeconomic research provide methods guidance, ensuring consistency in both the evidence and the decision-making process about drug reimbursement. This study reviewed the methodological quality of all 21 formally required pharmacoeconomic evaluations of new pharmaceuticals between 1 January 2005 and 1 October 2008, and verified whether these evaluations complied with pharmacoeconomic guidelines. Data on the quality of the pharmacoeconomic evaluations were extracted from the pharmacoeconomic reports published by the Dutch Health Care Insurance Board (CVZ). The Board's newsletters provided information on the advice to, and reimbursement decisions made by, the Dutch Minister of Health. All data extraction was carried out by two independent reviewers, and descriptive analyses were conducted. The methodological quality was sound in only 8 of the 21 pharmacoeconomic evaluations. In most cases, the perspective of analysis, the comparator drugs, and the reporting of both total and incremental costs and effects were correct. However, drug indication, form (i.e. cost utility/cost effectiveness) and time horizon of the evaluations were frequently flawed. Moreover, the costs and effects of the pharmaceuticals were not always analysed correctly, and modelling studies were often non-transparent. Twelve drugs were reimbursed, and nine were not. The compliance with pharmacoeconomic guidelines in economic evaluations of new pharmaceuticals can be improved. This would improve the methodological quality of the pharmacoeconomic evaluations and ensure consistency in the evidence and the decision-making process for drug reimbursement in the Netherlands.

Collaborative study using common samples to evaluate the performance of anti-drug antibody assays constructed by different companies.

PubMed

Niimi, Shingo; Nishimiya, Kazuhiro; Nishidate, Masanobu; Saito, Tetsu; Minoura, Kyoko; Kadotsuji, Kenta; Shimakura, Jin; Shigemizu, Hiroko; Hosogi, Jun; Adachi, Maiko; Hashimoto, Tsutomu; Mori, Tamiki; Harada, Hideki; Yamamoto, Ken-Ichi; Nakamura, Takahiro; Nomura, Tatsuki; Yamaguchi, Itadaki; Sonehara, Kazuhiko; Ishii-Watabe, Akiko; Kawasaki, Nana

2018-04-01

This study was undertaken to evaluate the performance of anti-drug antibody (ADA) assays constructed by each participating company using common samples including ADA, drug and human serum. The ADA assays constructed by each company showed good sensitivity and precision for evaluation of ADA. Cut points for screening and confirmatory assays and assay selectivity were determined by various calculation methods. In evaluations of blind ADA samples, nearly similar results were obtained by the study companies in determinations of whether samples were positive or negative except at the lowest sample concentration (5 ng/mL). In measurement of drug tolerance, for almost samples containing ADA and drugs, more positive results were obtained in assays using acid dissociation compared to those without acid dissociation. Overall, the performance of ADA assays constructed by the 10 companies participating in this study was acceptable in terms of sensitivity and reproducibility for detection and evaluation of immunogenicity in both patients and healthy subjects. On the other hand, based on results for samples containing ADA and drugs, validity of results for ADA assays conducted without acid dissociation was less meaningful and more difficult to evaluate. Thus, acid dissociation was confirmed to be useful for improving drug tolerance. Copyright © 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

21 CFR 900.5 - Evaluation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Evaluation. 900.5 Section 900.5 Food and Drugs... STANDARDS ACT MAMMOGRAPHY Accreditation § 900.5 Evaluation. FDA shall evaluate annually the performance of each accreditation body. Such evaluation shall include an assessment of the reports of FDA or State...

21 CFR 900.23 - Evaluation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Evaluation. 900.23 Section 900.23 Food and Drugs... STANDARDS ACT MAMMOGRAPHY States as Certifiers § 900.23 Evaluation. FDA shall evaluate annually the performance of each certification agency. The evaluation shall include the use of performance indicators that...

On illicit drug policies; methods of evaluation and comments on recent practices.

PubMed

Trovato, Giovanni; Vezzani, Antonio

2013-06-01

This contribution provides an overview of different approaches used to analyse drug policies within and across countries. Besides the great number of cost of illness studies which have contributed to the assessment of health harms and risks associated to the drug use, most of the recent efforts have focused on the creation of synthetic indices to classify countries around the world or to evaluate particular law enforcement policies in some countries. This is probably due to a general lack of comparable data across countries. The wide variety of budgetary practices in the drugs field in Europe contributes to the problems that exist in estimating drug-related public expenditure. These heterogeneous accounting practices, together with the complexity of the drug phenomenon and the multiplicity of perspectives on the issue, strongly constrains the possibility of economically evaluate and compare drug laws across countries.

How effective is drug abuse resistance education? A meta-analysis of Project DARE outcome evaluations.

PubMed Central

Ennett, S T; Tobler, N S; Ringwalt, C L; Flewelling, R L

1994-01-01

OBJECTIVES. Project DARE (Drug Abuse Resistance Education) is the most widely used school-based drug use prevention program in the United States, but the findings of rigorous evaluations of its effectiveness have not been considered collectively. METHODS. We used meta-analytic techniques to review eight methodologically rigorous DARE evaluations. Weighted effect size means for several short-term outcomes also were compared with means reported for other drug use prevention programs. RESULTS. The DARE effect size for drug use behavior ranged from .00 to .11 across the eight studies; the weighted mean for drug use across studies was .06. For all outcomes considered, the DARE effect size means were substantially smaller than those of programs emphasizing social and general competencies and using interactive teaching strategies. CONCLUSIONS. DARE's short-term effectiveness for reducing or preventing drug use behavior is small and is less than for interactive prevention programs. PMID:8092361

Drug Safety

MedlinePlus

... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

An interdisciplinary computational/experimental approach to evaluate drug-loaded gold nanoparticle tumor cytotoxicity

PubMed Central

Curtis, Louis T; England, Christopher G; Wu, Min; Lowengrub, John; Frieboes, Hermann B

2016-01-01

Aim: Clinical translation of cancer nanotherapy has largely failed due to the infeasibility of optimizing the complex interaction of nano/drug/tumor/patient parameters. We develop an interdisciplinary approach modeling diffusive transport of drug-loaded gold nanoparticles in heterogeneously-vascularized tumors. Materials & methods: Evaluated lung cancer cytotoxicity to paclitaxel/cisplatin using novel two-layer (hexadecanethiol/phosphatidylcholine) and three-layer (with high-density-lipoprotein) nanoparticles. Computer simulations calibrated to in-vitro data simulated nanotherapy of heterogeneously-vascularized tumors. Results: Evaluation of free-drug cytotoxicity between monolayer/spheroid cultures demonstrates a substantial differential, with increased resistance conferred by diffusive transport. Nanoparticles had significantly higher efficacy than free-drug. Simulations of nanotherapy demonstrate 9.5% (cisplatin) and 41.3% (paclitaxel) tumor radius decrease. Conclusion: Interdisciplinary approach evaluating gold nanoparticle cytotoxicity and diffusive transport may provide insight into cancer nanotherapy. PMID:26829163

In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development: focus on TB

PubMed Central

Vaddady, Pavan K; Lee, Richard E; Meibohm, Bernd

2011-01-01

For rapid anti-tuberculosis (TB) drug development in vitro pharmacokinetic/pharmacodynamic (PK/PD) models are useful in evaluating the direct interaction between the drug and the bacteria, thereby guiding the selection of candidate compounds and the optimization of their dosing regimens. Utilizing in vivo drug-clearance profiles from animal and/or human studies and simulating them in an in vitro PK/PD model allows the in-depth characterization of antibiotic activity of new and existing antibacterials by generating time–kill data. These data capture the dynamic interplay between mycobacterial growth and changing drug concentration as encountered during prolonged drug therapy. This review focuses on important PK/PD parameters relevant to anti-TB drug development, provides an overview of in vitro PK/PD models used to evaluate the efficacy of agents against mycobacteria and discusses the related mathematical modeling approaches of time–kill data. Overall, it provides an introduction to in vitro PK/PD models and their application as critical tools in evaluating anti-TB drugs. PMID:21359155

Assessment of a Pharmaceutical Advertisement Analysis Module in a Drug Literature Evaluation Course.

PubMed

Amin, Mohamed Ezzat Khamis; Fattouh, Youssef

2017-08-01

Objective. To evaluate the impact of an educational module on students' self-efficacy when analyzing the content of promotional drug brochures (PDBs) and to assess the students' value of PDBs' as an educational tool. Methods. Third-year bachelor of pharmacy students participated in a one-hour lecture and a two-hour laboratory. Students completed a survey before and after participating in the module. Results. The module elicited a statistically significant change in students' self-efficacy beliefs regarding evaluating promotional drug brochures, while the average perceived value of promotional drug brochures did not change significantly after the module. Conclusion. A brief educational module can increase students' self-efficacy in evaluating the content of PDBs.

Investing in Our Nation's Youth. National Youth Anti-Drug Media Campaign: Phase II (Final Report).

ERIC Educational Resources Information Center

Office of National Drug Control Policy, Washington, DC.

This publication presents the findings from an evaluation of Phase II of the National Youth Anti-Drug Media Campaign. The number one goal of the campaign was to educate youth to reject illegal drugs. This report evaluates Phase II and focuses on the effect of paid television advertising on awareness of anti-drug messages among youth, teens, and…

The usefulness and scientific accuracy of private sector Arabic language patient drug information leaflets.

PubMed

Sukkari, Sana R; Al Humaidan, Abdullah S; Sasich, Larry D

2012-07-01

Inadequate access to useful scientifically accurate patient information is a major cause of the inappropriate use of drugs resulting in serious personal injury and related costs to the health care system. The definition of useful scientifically accurate patient information for prescription drugs was accepted by the US Secretary of the Department of Health and Human Services in 1996 as that derived from or consistent with the US FDA approved professional product label for a drug. Previous quality content studies found that English language patient drug information leaflets distributed by US pharmacies failed to meet minimum criteria defining useful and scientifically accurate information. Evaluation forms containing the explicit elements that define useful scientifically accurate information for three drugs with known serious adverse drug reactions were created based on the current US FDA approved professional product labels. The Arabic language patient drug information leaflets for celecoxib, paroxetine, and lamotrigine were obtained locally and evaluated using a methodology similar to that used in previous quality content patient drug information studies in the US. The Arabic leaflets failed to meet the definition of useful scientifically accurate information. The celecoxib leaflet contained 30% of the required information and the paroxetine and lamotrigine leaflets contained 24% and 20%, respectively. There are several limitations to this study. The Arabic leaflets from only one commercial North American vendor were evaluated and the evaluation included a limited number of drugs. A larger study is necessary to be able to generalize these results. The study results are consistent with those of previous quality content studies of commercially available English patient drug information leaflets. The results have important implications for patients as access to a reliable source of drug information may prevent harm or limit the suffering from serious adverse drug reactions.

Evaluation of drug interaction microcomputer software: comparative study.

PubMed

Poirier, T I; Giudici, R

1991-01-01

Twelve drug interaction microcomputer software programs were evaluated and compared using general and specific criteria. This article summarizes and compares the features, ratings, advantages, and disadvantages of each program. Features of an ideal drug interaction program are noted. Recommended programs based on three price ranges are suggested.

21 CFR 1.101 - Notification and recordkeeping.

Code of Federal Regulations, 2011 CFR

2011-04-01

... products and devices regulated by the Center for Biologics Evaluation and Research—Division of Case... Research, Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-1448. (ii) For... Research—Division of New Drugs and Labeling Compliance, Center for Drug Evaluation and Research, Food and...

21 CFR 1.101 - Notification and recordkeeping.

Code of Federal Regulations, 2010 CFR

2010-04-01

... products and devices regulated by the Center for Biologics Evaluation and Research—Division of Case... Research, Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-1448. (ii) For... Research—Division of New Drugs and Labeling Compliance, Center for Drug Evaluation and Research, Food and...

[3D evaluation model for drug hepatotoxicity testing on HepG2 cells and its application in drug safety evaluation].

PubMed

Li, Dan-Dan; Tang, Xiang-Lin; Tan, Hong-Ling; Liang, Qian-de; Wang, Yu-Guang; Ma, Zeng-Chun; Xiao, Cheng-Rong; Gao, Yue

2016-04-01

3D in vitro toxicity testing model was developed by magnetic levitation method for culture of the human hepatoma cell line HepG2 and applied to evaluate the drug hepatotoxicity. After formation of stable 3D structure for HepG2 cells, their glycogen storage capacity under 2D and 3D culture conditions were detected by immunohistochemistry technology, and the mRNA expression levels of phase Ⅰ and Ⅱ drug metabolism enzymes, drug transporters, nuclear receptors and liver-specific marker albumin(ALB) were compared between 2D and 3D culture conditions by using RT-PCR method. Immunohistochemistry results showed that HepG2 cells had abundant glycogen storage capacity under 3D culture conditions, which was similar to human liver tissues. The mRNA expression levels of major drug metabolism enzymes, drug transporters, nuclear receptors and ALB in HepG2 cells under 3D culture conditions were up-regulated as compared with 2D culture conditions. For drug hepatotoxicity evaluation, the typical hepatotoxic drug acetaminophen(APAP), and most reported drugs Polygonum multiflorum Thunb.(Chinese name He-shou-wu) and Psoraleae corylifolia L.(Chinese name Bu-gu-zhi) were selected for single dose and repeated dose(7 d) exposure. In the repeated dose exposure test, 3D HepG2 cells showed higher sensitivity. This established 3D HepG2 cells model with magnetic levitation 3D culture techniques was more close to the human liver tissues both in morphology and functions, so it was a better 3D hepatotoxicity evaluation model. Copyright© by the Chinese Pharmaceutical Association.

Comparison of Generic-to-Brand Switchback Rates Between Generic and Authorized Generic Drugs.

PubMed

Hansen, Richard A; Qian, Jingjing; Berg, Richard; Linneman, James; Seoane-Vazquez, Enrique; Dutcher, Sarah K; Raofi, Saeid; Page, C David; Peissig, Peggy

2017-04-01

Generic drugs contain identical active ingredients as their corresponding brand drugs and are pharmaceutically equivalent and bioequivalent, whereas authorized generic drugs (AGs) contain both identical active and inactive ingredients as their corresponding brand drugs but are marketed as generics. This study compares generic-to-brand switchback rates between generic and AGs. Retrospective cohort study. Claims and electronic health record data from a regional U.S. health care system. The full cohort consisted of 5542 unique patients who received select branded drugs during the 6 months prior to their generic drug market availability (between 1999 and 2014) and then were switched to an AG or generic drug within 30 months of generic drug entry. For these patients, 5929 unique patient-drug combinations (867 with AGs and 5062 with generic drugs) were evaluated. Ten drugs with AGs and generics marketed between 1999 and 2014 were evaluated. The date of the first generic prescription was considered the index date for each drug, and it marked the beginning of follow-up to evaluate the occurrence of generic-to-brand switchback patterns over the subsequent 30 months. Switchback rates were compared between patients receiving AGs versus those receiving generics using multivariable Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson Comorbidity Score, pre-index drug use characteristics, and pre-index health care utilization. Among the 5542 unique patients who switched from brand to generic or brand to AG, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for AGs compared with generics (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15). The likelihood of switchback was higher for alendronate (HR 1.64, 95% CI 1.20-2.23) and simvastatin (HR 1.81, 95% CI 1.30-2.54) and lower for amlodipine (HR 0.27, 95% CI 0.17-0.42) compared with the other drugs evaluated. Overall switchback rates were similar between AG and generic drug users, indirectly supporting similar efficacy and tolerability profiles for brand and generic drugs. Reasons for differences in switchback rates among specific products need to be explored further. © 2017 Pharmacotherapy Publications, Inc.

[Quantitative Prediction of Drug-Drug Interaction Caused by CYP Inhibition and Induction from In Vivo Data and Its Application in Daily Clinical Practices-Proposal for the Pharmacokinetic Interaction Significance Classification System (PISCS)].

PubMed

Ohno, Yoshiyuki

2018-01-01

　Drug-drug interactions (DDIs) can affect the clearance of various drugs from the body; however, these effects are difficult to sufficiently evaluate in clinical studies. This article outlines our approach to improving methods for evaluating and providing drug information relative to the effects of DDIs. In a previous study, total exposure changes to many substrate drugs of CYP caused by the co-administration of inhibitor or inducer drugs were successfully predicted using in vivo data. There are two parameters for the prediction: the contribution ratio of the enzyme to oral clearance for substrates (CR), and either the inhibition ratio for inhibitors (IR) or the increase in clearance of substrates produced by induction (IC). To apply these predictions in daily pharmacotherapy, the clinical significance of any pharmacokinetic changes must be carefully evaluated. We constructed a pharmacokinetic interaction significance classification system (PISCS) in which the clinical significance of DDIs was considered in a systematic manner, according to pharmacokinetic changes. The PISCS suggests that many current 'alert' classifications are potentially inappropriate, especially for drug combinations in which pharmacokinetics have not yet been evaluated. It is expected that PISCS would contribute to constructing a reliable system to alert pharmacists, physicians and consumers of a broad range of pharmacokinetic DDIs in order to more safely manage daily clinical practices.

21 CFR 812.19 - Address for IDE correspondence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and Drug... Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705-1266. (b... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Address for IDE correspondence. 812.19 Section 812...

76 FR 59408 - Statement of Organizations, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... it has reorganized the Center for Drug Evaluation and Research (CDER) by establishing two offices and... for Drug Evaluation and Research (HFD-063), Food and Drug Administration, 11919 Rockville Pike, rm.... Provides Center oversight and leadership in the development of medical policy procedures and policy...

77 FR 48491 - Regulatory New Drug Review: Solutions for Study Data Exchange Standards; Notice of Meeting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... INFORMATION CONTACT: Ron Fitzmartin, Office of Planning & Informatics, Center for Drug Evaluation and Research... limited. Send registration information (including name, title, firm name, country of citizenship, address, telephone and fax number, and email address) to Fatima Elnigoumi, Center for Drug Evaluation and Research...

21 CFR 890.1925 - Isokinetic testing and evaluation system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Isokinetic testing and evaluation system. 890.1925 Section 890.1925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Diagnostic Devices § 890.1925...

21 CFR 890.1925 - Isokinetic testing and evaluation system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Isokinetic testing and evaluation system. 890.1925 Section 890.1925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Diagnostic Devices § 890.1925...

21 CFR 890.1925 - Isokinetic testing and evaluation system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Isokinetic testing and evaluation system. 890.1925 Section 890.1925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Diagnostic Devices § 890.1925...

21 CFR 890.1925 - Isokinetic testing and evaluation system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Isokinetic testing and evaluation system. 890.1925 Section 890.1925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Diagnostic Devices § 890.1925...

21 CFR 890.1925 - Isokinetic testing and evaluation system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Isokinetic testing and evaluation system. 890.1925 Section 890.1925 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Diagnostic Devices § 890.1925...

Drug Treatment in Adult Probation: An Evaluation of an Outpatient and Acupuncture Program.

ERIC Educational Resources Information Center

Moon, Melissa M.; Latessa, Edward J.

1994-01-01

The effectiveness of an innovative outpatient drug-free treatment facility serving felony drug offenders who are placed on probation is evaluated. Treatment included educational and group therapy as well as acupuncture. Background characteristics, levels of treatment, and selected outcomes are described. Principles of successful interventions are…

Drug Abuse Films, Second Edition.

ERIC Educational Resources Information Center

National Coordinating Council on Drug Education, Washington, DC.

This second edition updates and expands a 1971 evaluation of films and audiovisuals related to drug education performed by the National Coordinating Council on Drug Education. Materials in this edition are evaluated both for accuracy and effectiveness as a communications tool. They are separated into two sections--films and other audiovisuals…

21 CFR 640.25 - General requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., Center for Biologics Evaluation and Research, Food and Drug Administration. Such testing shall not be... undertaken by the Center for Biologics Evaluation and Research, Food and Drug Administration. [40 FR 4304... 21 Food and Drugs 7 2011-04-01 2010-04-01 true General requirements. 640.25 Section 640.25 Food...

21 CFR 201.25 - Bar code label requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857 (requests... Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Bar code label requirements. 201.25 Section 201.25...

21 CFR 807.90 - Format of a premarket notification submission.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and Drug... Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705-1266... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Format of a premarket notification submission. 807...

21 CFR 640.25 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., Center for Biologics Evaluation and Research, Food and Drug Administration. Such testing shall not be... undertaken by the Center for Biologics Evaluation and Research, Food and Drug Administration. [40 FR 4304... 21 Food and Drugs 7 2010-04-01 2010-04-01 false General requirements. 640.25 Section 640.25 Food...

21 CFR 640.56 - Quality control test for potency.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., Center for Biologics Evaluation and Research, Food and Drug Administration. Such testing shall not be... Evaluation and Research, Food and Drug Administration. (d) If the average potency level of antihemophilic... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Quality control test for potency. 640.56 Section...

Drug and Vaccine evaluation in the Human Aotus Plasmodium falciparum Model

DTIC Science & Technology

2011-05-01

and phenyl ring systems is anticipated to yield a valuable new antimalarial drug (33). The antimalarial activity and pharmacology of a series of...remains essentially unchanged since 1976, viz. to ascertain the antimalarial activity of drugs against P. falciparum and P. vivax in Aotus. The...Present data on the evaluation of potential antimalarial activity of drugs in the pre-clinical model of Aotus l. lemurinus (Panamanian night

Evaluation of certain veterinary drug residues in food. Eighty-first report of the Joint FAO/WHO Expert Committee on Food Additives.

PubMed

2016-01-01

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including MRLs for generic fish species, acute reference doses (ARfDs) for veterinary drugs, an approach for dietary exposure assessment of compounds used for multiple purposes (i.e veterinary drugs and pesticides), dietary exposure assessment for less-than-lifetime exposure, and the assessment of short-term (90-day and 12-month) studies in dogs. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two insecticides (diflubenzuron and teflubenzuron), an antiparasitic agent (ivermectin), an ectoparasiticide (sisapronil) and a β2-adrenoceptor agonist (zilpaterol hydrochloride). In addition, the Committee considered issues raised in concern forms from the Codex Committee on Residues of Veterinary Drugs in Foods on lasalocid sodium, an antiparasitic agent. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs), ARfDs and proposed MRLs.

Is Project Towards No Drug Abuse (Project TND) an evidence-based drug and violence prevention program? A review and reappraisal of the evaluation studies.

PubMed

Gorman, Dennis M

2014-08-01

This paper critically reviews the published evidence pertaining to Project Towards No Drug Abuse (Project TND). Publications from seven evaluation studies of Project TND are reviewed, and the results from these are discussed as related to the following outcomes: main effects on the use of cigarettes, alcohol and marijuana; main effects on the use of "hard drugs," defined in the evaluations as cocaine, hallucinogens, stimulants, inhalants, ecstasy and other drugs (e.g., depressants, PCP, steroids and heroin); subgroup and interaction analyses of drug use; and violence-related behaviors. Very few main effects have been found for cigarette, alcohol and marijuana use in the Project TND evaluations. While studies do report main effects for hard drug use, these findings are subject to numerous threats to validity and may be attributable to the data analyses employed. Similarly, while isolated subgroup and interaction effects were found for alcohol use among baseline nonusers and some violence-related behaviors in the early Project TND evaluations, these findings have not been replicated in more recent studies and may result from multiple comparisons between study conditions. In conclusion, there is little evidence to support the assertion that Project TND is an effective drug or violence prevention program. The broader implications of these findings for prevention science are discussed and suggestions are made as to how the quality of research in the field might be improved.

Drug use among men with unfulfilled wish to father children: a retrospective analysis and discussion of specific drug classes.

PubMed

Pompe, Sina V; Strobach, Dorothea; Stief, Christian G; Becker, Armin J; Trottmann, Matthias

2016-06-01

Male infertility is a multifactorial state. Among other risk factors, drugs can adversely affect male fertility and male sexual function. In a retrospective study we aimed to analyse how many involuntarily childless men seeking fertility evaluation consume drugs, which drugs and if these are potentially affecting male reproductive function. We retrospectively identified involuntarily childless men presenting for fertility evaluation at an andrologic outpatient department from 2011 to 2014. Medical records were searched for current drug use, age, diseases affecting male fertility, and number and kind of drugs. Drugs were classified according to their Anatomical Therapeutic Chemical code. Adverse drug reactions on male sexual function and fertility were searched in two independent literature sources. Drug use was documented for 244 of 522 patients (46.7%). The patients' mean age was 37.7 ± 8.7; the total number of drug intakes was 554 (mean 2.3 ± 1.9), corresponding to 201 different drugs. The most often involved Anatomical Therapeutic Chemical groups were nervous system (N), alimentary tract/metabolism (A), cardiovascular (C), and respiratory system (R) (n = 277; 50.0%). Fertility impairment was reported for 15.9%, and adverse drug reactions on male sexual function were found for 51.2% of all identified drugs. Underreporting of consumed drugs was likely, especially for non-prescription drugs. A high percentage of involuntarily childless men is taking drugs that can potentially influence male reproductive function. As drug intake represents a modifiable risk factor, fertility evaluation requires a comprehensive medication review including prescription and non-prescription drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of rational drug use based on World Health Organization core drug use indicators in selected public hospitals of eastern Ethiopia: a cross sectional study.

PubMed

Sisay, Mekonnen; Mengistu, Getnet; Molla, Bereket; Amare, Firehiwot; Gabriel, Tesfaye

2017-02-23

Despite the complexity of drug use, a number of indicators have been developed, standardized and evaluated by the World Health Organization (WHO). These indicators are grouped in to three categories namely: prescribing indicators, patient care indicators and facility indicators. The study was aimed to evaluate rational drug use based on WHO-core drug use indicators in Dilchora referral hospital, Dire Dawa; Hiwot Fana specialized university hospital, Harar and Karamara general hospital, Jigjiga, eastern Ethiopia. Hospital based quantitative cross sectional study design was employed to evaluate rational drug use based on WHO core drug use indicators in selected hospitals. Systematic random sampling for prescribing indicators and convenient sampling for patient care indicators was employed. Taking WHO recommendations in to account, a total of 1,500 prescription papers (500 from each hospitals) were investigated. In each hospital, 200 outpatient attendants and 30 key essential drugs were also selected using the WHO recommendation. Data were collected using retrospective and prospective structured observational check list. Data were entered to EPI Data Version 3.1, exported and analyzed using SPSS version 16.0. Besides, the data were evaluated as per the WHO guidelines. Statistical significance was determined by one way analysis of variance (ANOVA) for some variables. P-value of less than 0.05 was considered statistically significant. Finally, tabular presentation was used to present the data. Mean, 2.34 (±1.08) drugs were prescribed in the selected hospitals. Prescriptions containing antibiotics and that of injectables were 57.87 and 10.9% respectively. The average consultation and dispensing time were 276.5 s and 61.12 s respectively. Besides, 75.77% of the prescribed drugs were actually dispensed. Only 3.3% of prescriptions were adequately labeled and 75.7% patients know about the dosage of the prescription. Not more than, 20(66.7%) key drugs were available in stock while only 19(63.3%) of key drugs had adequate labeling. On average, selected key drugs were out of stock for 30 days per year. All of the hospitals included in the study used the national drug list, formulary and standard treatment guidelines but none of them had their own drug list or guideline. Majority of WHO stated core drug use indicators were not met by the three hospitals included in the study.

Regulatory aspects of oncology drug safety evaluation: past practice, current issues, and the challenge of new drugs.

PubMed

Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M Stacey; McGuinn, W David; Verbois, S Leigh

2010-03-01

The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

Evaluation of personal digital assistant drug information databases for the managed care pharmacist.

PubMed

Lowry, Colleen M; Kostka-Rokosz, Maria D; McCloskey, William W

2003-01-01

Personal digital assistants (PDAs) are becoming a necessity for practicing pharmacists. They offer a time-saving and convenient way to obtain current drug information. Several software companies now offer general drug information databases for use on hand held computers. PDAs priced less than 200 US dollars often have limited memory capacity; therefore, the user must choose from a growing list of general drug information database options in order to maximize utility without exceeding memory capacity. This paper reviews the attributes of available general drug information software databases for the PDA. It provides information on the content, advantages, limitations, pricing, memory requirements, and accessibility of drug information software databases. Ten drug information databases were subjectively analyzed and evaluated based on information from the product.s Web site, vendor Web sites, and from our experience. Some of these databases have attractive auxiliary features such as kinetics calculators, disease references, drug-drug and drug-herb interaction tools, and clinical guidelines, which may make them more useful to the PDA user. Not all drug information databases are equal with regard to content, author credentials, frequency of updates, and memory requirements. The user must therefore evaluate databases for completeness, currency, and cost effectiveness before purchase. In addition, consideration should be given to the ease of use and flexibility of individual programs.

Clinical report--guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations.

PubMed

Shaddy, Robert E; Denne, Scott C

2010-04-01

The proper ethical conduct of studies to evaluate drugs in children is of paramount importance to all those involved in these types of studies. This report is an updated revision to the previously published guidelines from the American Academy of Pediatrics in 1995. Since the previous publication, there have been great strides made in the science and ethics of studying drugs in children. There have also been numerous legislative and regulatory advancements that have promoted the study of drugs in children while simultaneously allowing for the protection of this particularly vulnerable group. This report summarizes these changes and advances and provides a framework from which to guide and monitor the ethical conduct of studies to evaluate drugs in children.

Development and Evaluation of Oral Controlled Release Chlorpheniramine-Ion Exchange Resinate Suspension

PubMed Central

Kadam, A. U.; Sakarkar, D. M.; Kawtikwar, P. S.

2008-01-01

An oral controlled release suspension of chlorpheniramine maleate was prepared using ion-exchange resin technology. A strong cation exchange resin Indion 244 was utilized for the sorption of the drug and the drug resinates was evaluated for various physical and chemical parameters. The drug-resinate complex was microencapsulated with a polymer Eudragit RS 100 to further retard the release characteristics. Both the drug-resinate complex and microencapsulated drug resinate were suspended in a palatable aqueous suspension base and were evaluated for controlled release characteristic. Stability study indicated that elevated temperature did not alter the sustained release nature of the dosage form indicating that polymer membrane surrounding the core material remained intact throughout the storage period. PMID:20046790

Development and evaluation of adsorption sheet (HD safe sheet-U) using active carbon for the purpose of the preventing the contamination diffusion of urinary excreted anticancer drug.

PubMed

Sato, Junya; Ohkubo, Haruka; Sasaki, Yuki; Yokoi, Makoto; Hotta, Yasunori; Kudo, Kenzo

2017-01-01

Certain amount of anticancer drugs is excreted in the urine of patients receiving anticancer drugs, and urinary scattering including anticancer drugs at excretion has become a route of anticancer drug contamination. Therefore, we developed an active carbon sheet (HD safe sheet-U) that prevented diffusion by adsorbing anticancer drugs including that excreted in urine. The present study conducted a performance evaluation of this sheet. The adsorption performance of active carbon to anticancer drug in the urine was evaluated by determining concentration changes in the active carbon suspension (5 mg/mL) of 14 kinds of anticancer drugs (cyclophosphamide, ifosfamide, carboplatin, cisplatin, methotrexate, 5-fluorouracil, cytarabine, gemcitabine, doxorubicin, epirubicin, paclitaxel, docetaxel, etoposide, and irinotecan) diluted with artificial urine. Adhesion of the anticancer drug dropping on the sheet to a slipper sole was evaluated because urine including anticancer drugs is scattered on the floor, which can spread by adhering to shoe soles of patients and healthcare workers. The performance of the active carbon sheet was compared with two other types of medical adsorption sheets used as control sheets. Anticancer drugs diluted with artificial urine (1 mL) were dropped on the active carbon sheet and the two control sheets. The sheets were trod with slippers made by polyvinyl chloride. The adhered anticancer drug was wiped off and its quantity was determined. A remarkable decrease in anticancer drug concentrations, except for cisplatin, was detected by mixture of active carbon in the artificial urine (0-79.6%). The quantity of anticancer drug adhesion to slipper soles from the active carbon sheet was significantly lower compared with that observed for the two control sheets for eight kinds of anticancer drugs (cyclophosphamide, ifosfamide, carboplatin, methotrexate, cytarabine, gemcitabine, doxorubicin, and docetaxel). There was no adhesion in cyclophosphamide and docetaxel. Furthermore, the quantities of adhesion in cytarabine, gemcitabine, doxorubicin, paclitaxel, and irinotecan were lower than determination limit. Active carbon might be effective in adsorbing urinary anticancer drugs. The active carbon sheet adsorbed urinary excreted anticancer drugs, and use of such sheets might prevent diffusion of contamination due to urinary excreted anticancer drugs.

[Application of fuzzy mathematics on modifying taste of oral solution of traditional Chinese drug].

PubMed

Wang, Youjie; Feng, Yi; Zhang, Bo

2009-01-01

To apply Fuzzy mathematical methods to choose the best taste modifying prescription of oral solution of traditional Chinese drug. Jin-Fukang oral solution was used as a model drug. The oral solution was prepared in different taste modifying prescriptions, whose tastes were evaluated by the fuzzy quality synthetic evaluation system. Compound-sweeteners with Sucralose and Erythritol was the best choice. Fuzzy integrated evaluation can be used to evaluate the taste of traditional Chinese medicinal pharmaceuticals, which overcame the artificial factors and achieve more objective conclusion.

Connection Map for Compounds (CMC): A Server for Combinatorial Drug Toxicity and Efficacy Analysis.

PubMed

Liu, Lei; Tsompana, Maria; Wang, Yong; Wu, Dingfeng; Zhu, Lixin; Zhu, Ruixin

2016-09-26

Drug discovery and development is a costly and time-consuming process with a high risk for failure resulting primarily from a drug's associated clinical safety and efficacy potential. Identifying and eliminating inapt candidate drugs as early as possible is an effective way for reducing unnecessary costs, but limited analytical tools are currently available for this purpose. Recent growth in the area of toxicogenomics and pharmacogenomics has provided with a vast amount of drug expression microarray data. Web servers such as CMap and LTMap have used this information to evaluate drug toxicity and mechanisms of action independently; however, their wider applicability has been limited by the lack of a combinatorial drug-safety type of analysis. Using available genome-wide drug transcriptional expression profiles, we developed the first web server for combinatorial evaluation of toxicity and efficacy of candidate drugs named "Connection Map for Compounds" (CMC). Using CMC, researchers can initially compare their query drug gene signatures with prebuilt gene profiles generated from two large-scale toxicogenomics databases, and subsequently perform a drug efficacy analysis for identification of known mechanisms of drug action or generation of new predictions. CMC provides a novel approach for drug repositioning and early evaluation in drug discovery with its unique combination of toxicity and efficacy analyses, expansibility of data and algorithms, and customization of reference gene profiles. CMC can be freely accessed at http://cadd.tongji.edu.cn/webserver/CMCbp.jsp .

Isobolographic analysis of the mechanisms of action of anticonvulsants from a combination effect.

PubMed

Matsumura, Nobuko; Nakaki, Toshio

2014-10-15

The nature of the pharmacodynamic interactions of drugs is influenced by the drugs׳ mechanisms of action. It has been hypothesized that drugs with different mechanisms are likely to interact synergistically, whereas those with similar mechanisms seem to produce additive interactions. In this review, we describe an extensive investigation of the published literature on drug combinations of anticonvulsants, the nature of the interaction of which has been evaluated by type I and II isobolographic analyses and the subthreshold method. The molecular targets of antiepileptic drugs (AEDs) include Na(+) and Ca(2+) channels, GABA type-A receptor, and glutamate receptors such as NMDA and AMPA/kainate receptors. The results of this review indicate that the nature of interactions evaluated by type I isobolographic analyses but not by the two other methods seems to be consistent with the above hypothesis. Type I isobolographic analyses may be used not only for evaluating drug combinations but also for predicting the targets of new drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical evaluation and use of urine screening for drug abuse.

PubMed Central

Saxon, A J; Calsyn, D A; Haver, V M; Delaney, C J

1988-01-01

Urine drug screening is indicated to evaluate patients who show mental status or behavioral changes and to monitor the abstinence of drug abusers. The appropriate timing for collecting urine specimens may vary depending on the suspected drug of abuse and on laboratory factors. Laboratories use a variety of techniques to do urine screens, and these must be understood by clinicians ordering the screens to interpret results correctly. In treating drug-abusing patients, clinicians must apply structured reinforcement in conjunction with urine screen results to aid patients in achieving abstinence. PMID:3176489

A Weighty Matter: Heaviness Influences the Evaluation of Disease Severity, Drug Effectiveness, and Side Effects

PubMed Central

Kaspar, Kai

2013-01-01

Peoples' perception of diseases and pharmaceutical drugs is a critical issue in health research. Beliefs about disease severity influence the compliance with recommendations for convalescence and the motivation to perform proper health-behavior. The estimated effectiveness of drugs and severity of side effects influence medication adherence and contribute to placebo effects. The present paper closes the gap between these effects and the concept of embodied cognition from a metaphor-enriched perspective. In five studies, we demonstrate that the bodily sensation of weight influences our evaluations of diseases and drugs. The experience of heaviness enhanced the estimated seriousness of diseases and the estimated effectiveness of drugs. The perceived seriousness of drug side effects was also affected by weight but only when drug effectiveness was not attended to. Moreover, the incidental sensation of weight shows a novel effect when evaluating weight-related drugs. The results are in line with the idea of embodied metaphors and reveal important boundary conditions which contribute to a better understanding of the underlying mechanisms. PMID:24244302

Accuracy and completeness of drug information in Wikipedia medication monographs.

PubMed

Reilly, Timothy; Jackson, William; Berger, Victoria; Candelario, Danielle

The primary objective of this study was to determine the accuracy and completeness of drug information on Wikipedia and Micromedex compared with U.S. Food and Drug Administration-approved U.S. product inserts. The top 10 brand and top 10 generic medications from the 2012 Institute for Health Informatics' list of top 200 drugs were selected for evaluation. Wikipedia medication information was evaluated and compared with Micromedex in 7 sections of drug information; the U.S. product inserts were used as the standard comparator. Wikipedia demonstrated significantly lower completeness and accuracy scores compared with Micromedex (mean composite scores 18.55 vs. 38.4, respectively; P <0.01). No difference was found between the mean composite scores for brand versus generic drugs in either reference (17.8 vs. 19.3, respectively [P = 0.62], for Wikipedia; 39.2 vs. 37.6, [P = 0.06] for Micromedex). Limitations to these results include the speed with which information is edited on Wikipedia, that there was no evaluation of off-label information, and the limited number of drugs that were evaluated. Wikipedia lacks the accuracy and completeness of standard clinical references and should not be a routine part of clinical decision making. More research should be conducted to evaluate the rationale for health care providers' use of Wikipedia. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Using Elite Athletes to Promote Drug Abstinence: Evaluation of a Single-Session School-Based Drug Use Prevention Program Delivered by Junior Hockey Players

ERIC Educational Resources Information Center

Wong, Jennifer

2016-01-01

School-based substance use prevention programs are a common method to approaching drug use in youths. Project SOS is a single-session drug prevention program developed by police officers and delivered by elite junior hockey players to students in grades 6 and 7. The current study evaluates the effects of Project SOS at achieving its objectives of…

Two-Drug Antimicrobial Chemotherapy: A Mathematical Model and Experiments with Mycobacterium marinum

PubMed Central

Ankomah, Peter; Levin, Bruce R.

2012-01-01

Multi-drug therapy is the standard-of-care treatment for tuberculosis. Despite this, virtually all studies of the pharmacodynamics (PD) of mycobacterial drugs employed for the design of treatment protocols are restricted to single agents. In this report, mathematical models and in vitro experiments with Mycobacterium marinum and five antimycobacterial drugs are used to quantitatively evaluate the pharmaco-, population and evolutionary dynamics of two-drug antimicrobial chemotherapy regimes. Time kill experiments with single and pairs of antibiotics are used to estimate the parameters and evaluate the fit of Hill-function-based PD models. While Hill functions provide excellent fits for the PD of each single antibiotic studied, rifampin, amikacin, clarithromycin, streptomycin and moxifloxacin, two-drug Hill functions with a unique interaction parameter cannot account for the PD of any of the 10 pairs of these drugs. If we assume two antibiotic-concentration dependent functions for the interaction parameter, one for sub-MIC and one for supra-MIC drug concentrations, the modified biphasic Hill function provides a reasonably good fit for the PD of all 10 pairs of antibiotics studied. Monte Carlo simulations of antibiotic treatment based on the experimentally-determined PD functions are used to evaluate the potential microbiological efficacy (rate of clearance) and evolutionary consequences (likelihood of generating multi-drug resistance) of these different drug combinations as well as their sensitivity to different forms of non-adherence to therapy. These two-drug treatment simulations predict varying outcomes for the different pairs of antibiotics with respect to the aforementioned measures of efficacy. In summary, Hill functions with biphasic drug-drug interaction terms provide accurate analogs for the PD of pairs of antibiotics and M. marinum. The models, experimental protocols and computer simulations used in this study can be applied to evaluate the potential microbiological and evolutionary efficacy of two-drug therapy for any bactericidal antibiotics and bacteria that can be cultured in vitro. PMID:22253599

A Public-Private Consortium Advances Cardiac Safety Evaluation: Achievements of the HESI Cardiac Safety Technical Committee

EPA Science Inventory

The evaluation of cardiovascular side-effects is a critical element in the development of all new drugs and chemicals. Cardiac safety issues have been and continue to be a major cause of attrition and withdrawal due to Adverse Drug Reactions (ADRs) in pharmaceutical drug developm...

Current Status of the Matson Evaluation of Drug Side Effects (MEDS)

ERIC Educational Resources Information Center

Matson, Johnny L.; Cervantes, Paige E.

2013-01-01

The Matson Evaluation of Drug Side Effects (MEDS) is currently the best established and most researched measure of drug side effects in the intellectual disability (ID) literature. Initial research was conducted on its psychometric properties such as reliability and validity. More recent research studies have used the measure to determine the…

77 FR 32124 - Guidance for Industry on Irritable Bowel Syndrome-Clinical Evaluation of Drugs for Treatment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-31

... sign or symptom recurrence. The section on trial endpoints was modified to note that a drug can be...] Guidance for Industry on Irritable Bowel Syndrome--Clinical Evaluation of Drugs for Treatment; Availability...: Submit either electronic or written comments on Agency guidances at any time. ADDRESSES: Submit written...

77 FR 23485 - Food and Drug Administration Patient Network Annual Meeting; Input Into Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

... specific disease area during its meetings with patients? For example, who should serve as representatives of patients? (2) What methodological and practical issues should FDA consider as it develops its... Research and Center for Biologics Evaluation and Research Efforts Center for Drug Evaluation and Research...

76 FR 65734 - Guidance for Industry on Evaluating the Safety of Flood-Affected Food Crops for Human Consumption...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0733] Guidance for Industry on Evaluating the Safety of Flood-Affected Food Crops for Human Consumption; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

49 CFR 242.115 - Substance abuse disorders and alcohol drug rules compliance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Substance abuse disorders and alcohol drug rules... CONDUCTORS Program and Eligibility Requirements § 242.115 Substance abuse disorders and alcohol drug rules... evaluated as not currently affected by a substance abuse disorder or that the person has been evaluated as...

49 CFR 242.115 - Substance abuse disorders and alcohol drug rules compliance.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Substance abuse disorders and alcohol drug rules... CONDUCTORS Program and Eligibility Requirements § 242.115 Substance abuse disorders and alcohol drug rules... evaluated as not currently affected by a substance abuse disorder or that the person has been evaluated as...

49 CFR 242.115 - Substance abuse disorders and alcohol drug rules compliance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Substance abuse disorders and alcohol drug rules... CONDUCTORS Program and Eligibility Requirements § 242.115 Substance abuse disorders and alcohol drug rules... evaluated as not currently affected by a substance abuse disorder or that the person has been evaluated as...

77 FR 35689 - Guidance for Industry on Irritable Bowel Syndrome-Clinical Evaluation of Drugs for Treatment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0146] Guidance for Industry on Irritable Bowel Syndrome--Clinical Evaluation of Drugs for Treatment; Availability...). The document announced the availability of a guidance for industry entitled ``Irritable Bowel Syndrome...

21 CFR 26.42 - Exchange and endorsement of product evaluation reports.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Exchange and endorsement of product evaluation reports. 26.42 Section 26.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... manufacturer's choice, type examination, and verification reports prepared to EC medical device requirements...

Juvenile Drug Court: Enhancing Outcomes by Integrating Evidence-Based Treatments

ERIC Educational Resources Information Center

Henggeler, Scott W.; Halliday-Boykins, Colleen A.; Cunningham, Phillippe B.; Randall, Jeff; Shapiro, Steven B.; Chapman, Jason E.

2006-01-01

Evaluated the effectiveness of juvenile drug court for 161 juvenile offenders meeting diagnostic criteria for substance abuse or dependence and determined whether the integration of evidence-based practices enhanced the outcomes of juvenile drug court. Over a 1-year period, a four-condition randomized design evaluated outcomes for family court…

21 CFR 570.20 - General principles for evaluating the safety of food additives.

Code of Federal Regulations, 2012 CFR

2012-04-01

... food additives. 570.20 Section 570.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES Food Additive Safety § 570.20 General principles for evaluating the safety of food additives. (a) In reaching a...

21 CFR 570.20 - General principles for evaluating the safety of food additives.

Code of Federal Regulations, 2013 CFR

2013-04-01

... food additives. 570.20 Section 570.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES Food Additive Safety § 570.20 General principles for evaluating the safety of food additives. (a) In reaching a...

21 CFR 570.20 - General principles for evaluating the safety of food additives.

Code of Federal Regulations, 2014 CFR

2014-04-01

... food additives. 570.20 Section 570.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES Food Additive Safety § 570.20 General principles for evaluating the safety of food additives. (a) In reaching a...

An Evaluation of an Innovative Drug Education Program: First Year Results.

ERIC Educational Resources Information Center

Schaps, Eric; And Others

An innovative drug education course was taught to seventh and eighth graders and evaluated in a true experiment. Students learned Lasswell's framework for understanding human needs and motives, a systematic decision-making procedure, and information about the pharmacological, psychological, and social consequences of licit and illicit drug use.…

Availability of drug information on community pharmacy websites in Tennessee.

PubMed

Borja-Hart, Nancy; Hohmeier, Kenneth C

2017-06-01

This study reports the availability and type of drug information resources on community pharmacy websites in Tennessee. A list of pharmacies was obtained from the Tennessee Board of Pharmacy. All community pharmacies located in Tennessee with a website were evaluated. Community pharmacy websites that listed a drug information resource were further analysed into pharmacy type and drug information provider. One hundred and sixty-nine websites were evaluated. Thirty-six websites listed a drug information resource. Fifty per cent of those sites used the drug information provider RxWiki. Other providers included drugs.com, First Data Bank, A.D.A.M., RxList, Gold Standard Multimedia and Express Scripts. Community pharmacy websites are underutilized as a provider for credible drug information for the public. © 2017 Royal Pharmaceutical Society.

Rational drug therapy education in clinical phase carried out by task-based learning

PubMed Central

Bilge, S. Sırrı; Akyüz, Bahar; Ağrı, Arzu Erdal; Özlem, Mıdık

2017-01-01

Objectives: Irrational drug use results in drug interactions, treatment noncompliance, and drug resistance. Rational pharmacotherapy education is being implemented in many faculties of medicine. Our aim is to introduce rational pharmacotherapy education by clinicians and to evaluate task-based rational drug therapy education in the clinical context. Methods: The Kirkpatrick's evaluation model was used for the evaluation of the program. The participants evaluated the program in terms of constituents of the program, utilization, and contribution to learning. Voluntary participants responded to the evaluation forms after the educational program. Data are evaluated using both quantitative and qualitative tools. SPSS (version 21) used for quantitative data for determining mean and standard deviation values. Descriptive qualitative analysis approach is used for the analysis of open-ended questions. Results: It was revealed that the program and its components have been favorable. A total 95.9% of the students consider the education to be beneficial. Simulated patients practice and personal drug choice/problem-based learning sessions were appreciated by the students in particular. 93.9% of the students stated that all students of medicine should undergo this educational program. Among the five presentations contained in the program, “The Principles of Prescribing” received the highest points (9 ± 1.00) from participating students in general evaluation of the educational program. Conclusion: This study was carried out to improve task-based rational drug therapy education. According to feedback from the students concerning content, method, resource, assessment, and program design; some important changes, especially in number of facilitators and indications, are made in rational pharmacotherapy education in clinical task-based learning program. PMID:28458432

76 FR 78670 - Draft Guidance for Industry and Food and Drug Administration Staff; Evaluation of Sex Differences...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

...] Draft Guidance for Industry and Food and Drug Administration Staff; Evaluation of Sex Differences in... entitled ``Evaluation of Sex Differences in Medical Device Clinical Studies.'' This document provides guidance on the study and evaluation of sex differences in medical device clinical trials, with a specific...

Institutional formularies: the relevance of pharmacoeconomic analysis to formulary decisions.

PubMed

Lipsy, R J

1992-04-01

Formularies, in one form or another, have been in existence for nearly 100 years. Beginning simply as a list of available agents, the formulary has evolved into a complex system which acts as a guide to prescribing practices. As the importance of the formulary has increased, so has the need for formulary managers to make an appropriate decision about each drug's formulary status. Several systematic approaches to drug evaluations have been developed to aid in the decision process. However, while some reviews of drug utilisation contain fairly rigorous analyses of their clinical efficacy, very few include an economic evaluation that goes beyond the cost of drug acquisition, preparation, distribution and administration. This is surprising, since formulary managers rank economic data second only to clinical data when making formulary decisions. In the past this apparent oversight has been due, in part, to the absence of a sophisticated model which can both approximate a drug's true economic impact and express cost and quality in similar terms. The explosion of new and very expensive biotechnology drugs into the market has the potential to improve patient care significantly. Such drugs also have the potential to increase institutional pharmacy budgets significantly; with some analysts predicting a spending of $US60 million yearly for these drugs by the year 2000, critical evaluation will be mandatory. Fortunately, advances in the relatively new science of pharmacoeconomics have made it possible to conduct appropriate estimates of the true economic impact of new drug therapies. Pharmacoeconomic studies can be very useful in evaluating drugs for formulary inclusion and in assessing the effects of formulary changes on institutional budgets. Cost-effectiveness and cost-benefit analyses, utilising decision analysis models and/or data gathered from clinical studies, are used most frequently. Relatively simple models can be used to evaluate drugs within the same class if sufficient published data on their clinical efficacy and safety are available. More complex analyses are necessary when comparing dissimilar agents or when comparing agents with non-drug therapy. Pharmacoeconomic studies have frequently been used to demonstrate that very substantial direct costs of drug therapy are often offset by equal or greater reductions in other institutional direct and indirect patient care costs. Pharmacoeconomic studies have also been used to calculate the relative cost-effectiveness of drug therapies for different disease states, although such evaluations are more useful to governmental and regulatory agencies than to individual institutions.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design

NASA Astrophysics Data System (ADS)

Ishikawa, Toshihisa; Tamura, Ai; Saito, Hikaru; Wakabayashi, Kanako; Nakagawa, Hiroshi

2005-10-01

In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development. Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines. Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least 30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may greatly facilitate drug development and allow the prediction of drug-drug interactions. We recently developed methods for high-speed functional screening and quantitative structure-activity relationship analysis to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues that can circumvent AGCG2-associated multidrug resistance of cancer.

The Two Faces of Social Interaction Reward in Animal Models of Drug Dependence.

PubMed

El Rawas, Rana; Saria, Alois

2016-03-01

Drug dependence is a serious health and social problem. Social factors can modify vulnerability to developing drug dependence, acting as risk factors or protective factors. Whereas stress and peer environment that encourage substance use may increase drug taking, strong attachments between family members and peer environment that do not experience drug use may protect against drug taking and, ultimately, drug dependence. The rewarding effects of drug abuse and social interaction can be evaluated using animal models. In this review we focus on evaluating social interaction reward in the conditioned place preference paradigm. We give an overview of how social interaction, if made available within the drug context, may facilitate, promote and interact with the drug's effects. However, social interaction, if offered alternatively outside the drug context, may have pronounced protective effects against drug abuse and relapse. We also address the importance of the weight difference parameter between the social partners in determining the positive or "agonistic" versus the hostile or "antagonistic" social interaction. We conclude that understanding social interaction reward and its subsequent effects on drug reward is sorely needed for therapeutic interventions against drug dependence.

[Evaluation of Dissolution Profiles of Famotidine from Over-the-counter Drugs].

PubMed

Saito, Yuji; Adachi, Naoki; Kato, Miki; Nadai, Masayuki

2018-03-27

  In recent years, self-medication has started to receive more attention in Japan owing to increasing medical costs and health awareness among people. One of the main roles of pharmacists in self-medication is to provide appropriate information regarding over-the-counter (OTC) drugs. However, pharmacists promoting the proper use of OTC drugs have little information on their formulation properties. In this study, we performed dissolution tests on both OTC drugs and ethical drug (ED) containing famotidine, and evaluated the differences in their dissolution profiles. Marked differences in dissolution profiles of OTC drugs were observed in test solutions at pH 1.2, 4.0, and 6.8 and in water. To evaluate the differences quantitatively, we calculated the lag time and dissolution rate constant from the dissolution profiles. Significant differences in lag times and dissolution rate constants between some OTC drugs and ED were observed. We also used similarity factor (f2), to quantify the similarity between dissolution profiles of OTC drugs and ED. f2 values less than 42 were observed in some OTC drugs, suggesting that these differences might influence absorption in vivo resulting in differences in their onset time and efficacy. The findings of this study will provide useful information for the promotion of proper use of OTC drugs.

Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

PubMed

Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

2012-08-01

Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process.

PubMed

Huang, Shiew-Mei; Strong, John M; Zhang, Lei; Reynolds, Kellie S; Nallani, Srikanth; Temple, Robert; Abraham, Sophia; Habet, Sayed Al; Baweja, Raman K; Burckart, Gilbert J; Chung, Sang; Colangelo, Philip; Frucht, David; Green, Martin D; Hepp, Paul; Karnaukhova, Elena; Ko, Hon-Sum; Lee, Jang-Ik; Marroum, Patrick J; Norden, Janet M; Qiu, Wei; Rahman, Atiqur; Sobel, Solomon; Stifano, Toni; Thummel, Kenneth; Wei, Xiao-Xiong; Yasuda, Sally; Zheng, Jenny H; Zhao, Hong; Lesko, Lawrence J

2008-06-01

Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling.

Drug exposure in register-based research—An expert-opinion based evaluation of methods

PubMed Central

Taipale, Heidi; Koponen, Marjaana; Tolppanen, Anna-Maija; Hartikainen, Sirpa; Ahonen, Riitta; Tiihonen, Jari

2017-01-01

Background In register-based pharmacoepidemiological studies, construction of drug exposure periods from drug purchases is a major methodological challenge. Various methods have been applied but their validity is rarely evaluated. Our objective was to conduct an expert-opinion based evaluation of the correctness of drug use periods produced by different methods. Methods Drug use periods were calculated with three fixed methods: time windows, assumption of one Defined Daily Dose (DDD) per day and one tablet per day, and with PRE2DUP that is based on modelling of individual drug purchasing behavior. Expert-opinion based evaluation was conducted with 200 randomly selected purchase histories of warfarin, bisoprolol, simvastatin, risperidone and mirtazapine in the MEDALZ-2005 cohort (28,093 persons with Alzheimer’s disease). Two experts reviewed purchase histories and judged which methods had joined correct purchases and gave correct duration for each of 1000 drug exposure periods. Results The evaluated correctness of drug use periods was 70–94% for PRE2DUP, and depending on grace periods and time window lengths 0–73% for tablet methods, 0–41% for DDD methods and 0–11% for time window methods. The highest rate of evaluated correct solutions for each method class were observed for 1 tablet per day with 180 days grace period (TAB_1_180, 43–73%), and 1 DDD per day with 180 days grace period (1–41%). Time window methods produced at maximum only 11% correct solutions. The best performing fixed method TAB_1_180 reached highest correctness for simvastatin 73% (95% CI 65–81%) whereas 89% (95% CI 84–94%) of PRE2DUP periods were judged as correct. Conclusions This study shows inaccuracy of fixed methods and the urgent need for new data-driven methods. In the expert-opinion based evaluation, the lowest error rates were observed with data-driven method PRE2DUP. PMID:28886089

77 FR 64346 - Nonprescription Drugs Advisory Committee; Amendment of Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-19

... for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Building 31... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Nonprescription Drugs Advisory Committee; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION...

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

PubMed Central

Weersink, Rianne A; Bouma, Margriet; Burger, David M; Drenth, Joost P H; Hunfeld, Nicole G M; Kranenborg, Minke; Monster-Simons, Margje H; van Putten, Sandra A W; Metselaar, Herold J; Taxis, Katja; Borgsteede, Sander D

2016-01-01

Introduction Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. Methods and analysis For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. Ethics and dissemination Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings. PMID:27733414

Assessing the Quality of Economic Evaluations of FDA Novel Drug Approvals: A Systematic Review.

PubMed

Woersching, Alex L; Borrego, Matthew E; Raisch, Dennis W

2016-12-01

To systematically review and assess the quality of the novel drugs' economic evaluation literature in print during the drugs' early commercial availability following US regulatory approval. MEDLINE and the United Kingdom National Health Service Economic Evaluation Database were searched from 1946 through December 2011 for economic evaluations of the 50 novel drugs approved by the FDA in 2008 and 2009. The inclusion criteria were English-language, peer-reviewed, original economic evaluations (cost-utility, cost-effectiveness, cost-minimization, and cost-benefit analyses). We extracted and analyzed data from 36 articles considering 19 of the 50 drugs. Two reviewers assessed each publication's quality using the Quality of Health Economic Studies (QHES) instrument and summarized study quality on a 100-point scale. Study quality had a mean of 70.0 ± 16.2 QHES points. The only study characteristics associated with QHES score (with P < 0.05) were having used modeling or advanced statistics, 75.1 versus 61.9 without; using quality-adjusted life years as an outcome, 75.9 versus 64.7 without; and cost-utility versus cost-minimization analysis, 75.9 versus 58.7. Studies most often satisfied quality aspects about stating study design choices and least often satisfied aspects about justifying design choices. The reviewed literature considered a minority of the 2008-2009 novel drugs and had mixed study quality. Cost-effectiveness stakeholders might benefit from efforts to improve the quality and quantity of literature examining novel drugs. Editors and reviewers may support quality improvement by stringently imposing economic evaluation guidelines about justifying study design choices. © The Author(s) 2016.

Pharmaceutical policies: effects of cap and co-payment on rational drug use.

PubMed

Austvoll-Dahlgren, A; Aaserud, M; Vist, G; Ramsay, C; Oxman, A D; Sturm, H; Kösters, J P; Vernby, A

2008-01-23

Growing expenditures on prescription drugs represent a major challenge to many health systems. Cap and co-payment (direct cost-share) policies are intended as an incentive to deter unnecessary or marginal utilisation, and to reduce third-party payer expenditures by shifting parts of the financial burden from the insurer to patients, thus increasing their financial responsibility for prescription drugs. Direct patient drug payment policies include caps (maximum number of prescriptions or drugs that are reimbursed), fixed co-payments (patients pay a fixed amount per prescription or drug), coinsurance (patients pay a percent of the price), ceilings (patients pay the full price or part of the cost up to a ceiling, after which drugs are free or available at reduced cost), and tier co-payments (differential co-payments usually assigned to generic and brand drugs). To determine the effects of cap and co-payment (cost-sharing) policies on drug use, healthcare utilisation, health outcomes and costs (expenditures). We searched the following databases and web sites: Effective Practice and Organisation of Care Group Register (date of last search: 6 September 07), Cochrane Central Register of Controlled Trials (27 August 07), MEDLINE (29 August 07), EMBASE (29 August 07), NHS EED (27 August 07), ISI Web of Science (09 January 07), CSA Worldwide Political Science Abstracts (21 October 03), EconLit (23 October 03), SIGLE (12 November 03), INRUD (21 November 03), PAIS International (23 March 04), International Political Science Abstracts (09 January 04), PubMed (25 February 04), NTIS (03 March 04), IPA (22 April 04), OECD Publications & Documents (30 August 05), SourceOECD (30 August 05), World Bank Documents & Reports (30 August 05), World Bank e-Library (04 May 05), JOLIS (22 February 06), Global Jolis (22 February 06), WHOLIS(22 February 06), WHO web site browsed (25 August 05). We defined policies in this review as laws, rules, or financial or administrative orders made by governments, non-government organisations or private insurers. We included randomised controlled trials, non-randomised controlled trials, interrupted time series analyses, repeated measures studies and controlled before-after studies of cap or co-payment policies for a large jurisdiction or system of care. To be included, a study had to include an objective measure of at least one of the following outcomes: drug use, healthcare utilisation, health outcomes or costs (expenditures). Two authors independently extracted data and assessed study limitations. We undertook quantitative analysis of time series data for studies with sufficient data. We included 30 evaluations (in 21 studies). Of these, 11 evaluated fixed co-payment, six evaluated coinsurance with a ceiling, four evaluated caps, three evaluated fixed co-payment with a ceiling, three evaluated tier co-payment, one evaluated ceiling, one evaluated fixed co-payment and coinsurance with a ceiling, and one evaluated a fixed co-payment with a cap. Most of the included evaluations were observational studies and the quality of the evidence was found to be generally low to moderate. Introducing or increasing direct co-payments reduced drug use and saved plan drug expenditures across studies. Patients responded through drug discontinuation or by cost-sharing. Investigators found reductions for life-sustaining drugs or drugs that are important in treating chronic conditions as well as other drugs. Few studies reported on the effects on health and healthcare utilisation. One study found adverse effects on health through increased healthcare utilisation when a cap was introduced in a vulnerable population. No statistically significant change in use of healthcare services was found in other studies when a cap was introduced on a drug considered over-prescribed in a vulnerable population, or following a shift from a two-tier to a three-tier system with increased co-payments for tier-1 drugs in a general population. We found a diversity of cap and co-payment policies. Poor reporting of the intensity of interventions and differences in setting, populations and interventions made it difficult to make comparisons across studies. Cap and co-payment polices can reduce drug use and save plan drug expenditures. However, although insufficient data on health outcomes were available, substantial reductions in the use of life-sustaining drugs or drugs that are important in treating chronic conditions may have adverse effects on health, and as a result increase the use of healthcare services and overall expenditures. Direct payments are less likely to cause harm if only non-essential drugs are included or exemptions are built in to ensure that patients receive needed medical care.

Drug reimbursement decision-making in Thailand, China, and South Korea.

PubMed

Ngorsuraches, Surachat; Meng, Wei; Kim, Bo-Yeon; Kulsomboon, Vithaya

2012-01-01

To provide a comparison of national drug reimbursement decision-making, including an update of economic evaluation roles and barriers, in Thailand, China, and South Korea. Documentary reviews supplemented by experiences of policymakers. National health insurance policy in all the three countries has been developed toward coverage for all. It leads to higher health-care expenditures and requires a good reimbursement system for health-care services, including drugs. Drug reimbursement decision-making in these countries is to develop a reimbursement list with the help of various committees having different roles. Primarily, they assess the clinical and safety evidence. Economic evidence, including budget impact and pharmacoeconomic evaluation, has also been very important for their reimbursement decision-making. This evidence is sometimes used in negotiation mechanism, which allows pharmaceutical companies to lower their drug prices and leads to lower overall drug expenditures. Several common barriers, for example, human capacity and data availability, for obtaining economic evidence in all the three countries, however, still exist. Drug reimbursement decision-making in Thailand, China, and South Korea is in its transition period. It seems to run in the same direction, for example, guideline development and pharmacoeconomic evaluation agency establishment. Pharmacoeconomic evaluation plays important roles in the efficiency of drug reimbursement decision-making, even though there are several barriers to be overcome. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Preparation, In Vitro Characterization, and In Vivo Pharmacokinetic Evaluation of Respirable Porous Microparticles Containing Rifampicin

PubMed Central

Kundawala, Aliasgar; Patel, Vishnu; Patel, Harsha; Choudhary, Dhaglaram

2014-01-01

Abstract This study aimed to prepare and evaluate rifampicin microparticles for the lung delivery of rifampicin as respirable powder. The microparticles were prepared using chitosan by the spray-drying method and evaluated for aerodynamic properties and pulmonary drug absorption. To control the drug release, tripoly-phosphate in different concentrations 0.6, 0.9, 1.2, and 1.5 was employed to get a sustained drug release profile. The microparticles were evaluated for drug loading, % entrapment efficiency, tapped density, morphological characteristics, and in vitro drug release studies. Aerosol properties were determined using the Andersen cascade impactor. Porous microparticles with particle sizes (d0.5) less than 10 μm were obtained. The entrapment of rifampicin in microparticles was up to 72%. In vitro drug release suggested that the crosslinked microparticles showed sustained release for more than 12 hrs. The drug release rate was found to be decreased as the TPP concentration was increased. The microparticles showed a fine particle fraction in the range of 55–63% with mass median aerodynamic diameter (MMAD) values below 3 μm. The in vivo pulmonary absorption of the chitosan microparticles suggested a sustained drug release profile up to 72 hrs with an elimination rate of 0.010 per hr. The studies revealed that the spray-dried porous microparticles have suitable properties to be used as respirable powder in rifampicin delivery to the lungs. PMID:25853075

Information for Consumers (Drugs)

MedlinePlus

... Evaluation and Mitigation Strategies (REMS) REMS is a risk management plan required by FDA for certain prescription drugs, that uses tools beyond routine professional labeling to ensure that the benefits of the drug outweigh its risks. Index to Drug - Specific Information List of drugs ...

Nano-sized crystalline drug production by milling technology.

PubMed

Moribe, Kunikazu; Ueda, Keisuke; Limwikrant, Waree; Higashi, Kenjirou; Yamamoto, Keiji

2013-01-01

Nano-formulation of poorly water-soluble drugs has been developed to enhance drug dissolution. In this review, we introduce nano-milling technology described in recently published papers. Factors affecting the size of drug crystals are compared based on the preparation methods and drug and excipient types. A top-down approach using the comminution process is a method conventionally used to prepare crystalline drug nanoparticles. Wet milling using media is well studied and several wet-milled drug formulations are now on the market. Several trials on drug nanosuspension preparation using different apparatuses, materials, and conditions have been reported. Wet milling using a high-pressure homogenizer is another alternative to preparing production-scale drug nanosuspensions. Dry milling is a simple method of preparing a solid-state drug nano-formulation. The effect of size on the dissolution of a drug from nanoparticles is an area of fundamental research, but it is sometimes incorrectly evaluated. Here, we discuss evaluation procedures and the associated problems. Lastly, the importance of quality control, process optimization, and physicochemical characterization are briefly discussed.

21 CFR 314.98 - Postmarketing reports.

Code of Federal Regulations, 2010 CFR

2010-04-01

... for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Postmarketing reports. 314.98 Section 314.98 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR...

77 FR 59624 - Gastrointestinal Drugs Advisory Committee; Notice of Postponement of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... FURTHER INFORMATION CONTACT: Cindy Hong, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Gastrointestinal Drugs Advisory Committee; Notice of Postponement of Meeting AGENCY: Food and Drug Administration...

78 FR 42088 - Anesthetic and Analgesic Drug Products Advisory Committee; Cancellation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Anesthetic and Analgesic Drug Products Advisory Committee; Cancellation AGENCY: Food and Drug Administration..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31...

78 FR 13686 - Draft Guidance for Industry and Review Staff on Pediatric Information Incorporated Into Human...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-28

... Prescription Drug and Biological Products Labeling; Availability AGENCY: Food and Drug Administration, HHS... (BPCA) and the Pediatric Research Equity Act (PREA), as amended by the Food and Drug Administration... Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New...

Saginaw Drug and Alcohol Abuse Education and Training Program: Product Evaluation, 1990-1991.

ERIC Educational Resources Information Center

Saginaw Public Schools, MI. Dept. of Evaluation Services.

This report evaluates the Saginaw Drug and Alcohol Abuse Education Training Program conducted in 1990-1991, which provided in-depth training for 94 professionals including 63 teachers and 7 counselors through a workshop lasting 5 days and containing 6 hours of instruction per day. The workshops addressed the identification of both drug abuse…

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

Drug Abuse Prevention: Report of the Temporary State Commission to Evaluate the Drug Laws.

ERIC Educational Resources Information Center

Betros, Emeel S.; And Others

The findings and recommendations of the Temporary State Commission to Evaluate the Drug Laws, set forth in the introduction to this report, are based on questionnaires to prevention experts and professionals responsible for child and adolescent care, on communications with community agencies, and on statewide public hearings. The committee found…

75 FR 54349 - Animal Models-Essential Elements To Address Efficacy Under the Animal Rule; Notice of Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-07

... Biologics Evaluation and Research (HFM-49), Food and Drug Administration, 1401 Rockville Pike, suite 200N... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6183, Silver... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0007...

21 CFR 314.200 - Notice of opportunity for hearing; notice of participation and request for hearing; grant or...

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Notice of opportunity for hearing. The Director of the Center for Drug Evaluation and Research, Food and..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver... Amendments of 1962, is required to be supported by evidence of past and present quantitative formulas...

21 CFR 314.200 - Notice of opportunity for hearing; notice of participation and request for hearing; grant or...

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Notice of opportunity for hearing. The Director of the Center for Drug Evaluation and Research, Food and..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver... Amendments of 1962, is required to be supported by evidence of past and present quantitative formulas...

21 CFR 314.200 - Notice of opportunity for hearing; notice of participation and request for hearing; grant or...

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Notice of opportunity for hearing. The Director of the Center for Drug Evaluation and Research, Food and..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver... Amendments of 1962, is required to be supported by evidence of past and present quantitative formulas...

21 CFR 314.200 - Notice of opportunity for hearing; notice of participation and request for hearing; grant or...

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Notice of opportunity for hearing. The Director of the Center for Drug Evaluation and Research, Food and..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver... Amendments of 1962, is required to be supported by evidence of past and present quantitative formulas...

21 CFR 314.200 - Notice of opportunity for hearing; notice of participation and request for hearing; grant or...

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Notice of opportunity for hearing. The Director of the Center for Drug Evaluation and Research, Food and..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver... Amendments of 1962, is required to be supported by evidence of past and present quantitative formulas...

Preparation and Evaluation of Herbal Shampoo Powder

PubMed Central

Dubey, Sachin; Nema, Neelesh; Nayak, S.

2004-01-01

Two preparations of herbal shampoo powder were formulated using some common traditional drugs used by folk and traditional people of Bundelkhand region (M.P) India, for hair care. The preparations were formulated using bahera, amla, neem tulsi, shikakai henna & brahmi evaluated for organoleptic, powder charecterestics, foam test and physical evaluation. As the selected drugs being used since long time as single drug or in combination, present investigations will further help to establish a standard formulation and evaluation parameters, which will certainly help in the standardization for quality and purity of such type of herbal powder shampoos. PMID:22557149

An approach to evaluating drug-nutrient interactions.

PubMed

Santos, Cristina A; Boullata, Joseph I

2005-12-01

Although the significance of interactions between drugs is widely appreciated, little attention has been given to interactions between drugs and nutrients. Pharmacists are challenged to remember documented interactions involving available drugs, and they face the possibility that each newly approved therapeutic agent may be involved not only in unrecognized drug-drug interactions but in drug-nutrient interactions as well. A more consistent approach to evaluating drug-nutrient interactions is needed. The approach must be systematic in order to assess the influence of nutritional status, food, or specific nutrients on a drug's pharmacokinetics and pharmacodynamics, as well as the influence of a drug on overall nutritional status or on the status of a specific nutrient. We provide such a process, using several recently approved drugs as working examples. Risk factors and clinical relevance are described, with distinctions made between documented and potential interactions. Application of this process by the pharmacist to any drug will help increase their expertise. Furthermore, full consideration by pharmacists of all possible interactions of the drug regimens used in practice can allow for improved patient care.

Staff Working Papers of the Drug Law Evaluation Project. A Companion Volume to the Final Report of the Joint Committee of New York Drug Law Evaluation.

ERIC Educational Resources Information Center

1978

The papers in this volume were prepared as part of an evaluation of the effects of the strict 1973 New York State drug laws. The first paper explores the effects of the laws on heroin use. It analyzes the trends of various indicators of heroin use in New York State over a period of several years. In order to isolate movements unique to New York,…

A review of the evaluation of 47 drug abuse prevention curricula available nationally.

PubMed

Dusenbury, L; Falco, M; Lake, A

1997-04-01

This review determined how many drug prevention curricula available to schools have been shown in rigorous research studies to reduce substance use behavior. Forty-seven curricula which met the following criteria were included: 1) they focused on primary prevention of alcohol and/or drug use, 2) they were classroom-based curricula designed for any grade level P-12, 3) they were nationally and currently available, and 4) program distributors were willing to provide samples of curriculum materials to determine drug abuse prevention content. Of the 47 drug abuse prevention curricula identified, 10 (21%) had been subjected to sufficiently rigorous evaluations. At least eight of the 10 programs have been shown effective at reducing tobacco or drug use, in at least some studies. The remaining two programs did not appear to have sustained effects on drug use, although they had variable success at reducing substance use early on. One of the 10 programs has been shown to have positive effects lasting into young adulthood. Six of the 10 curricula have been shown to have effects lasting for at least two years after the pretest. Two curricula have not been evaluated beyond the post-test, so it is impossible to know whether their effectiveness will last. Recommendations to increase the number of programs rigorously evaluated are offered.

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

PubMed Central

Liu, Hongzhuo; Feng, Liang; Tolia, Gaurav; Liddell, Mark R.; Hao, Jinsong; Li, S. Kevin

2013-01-01

A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)–poly(ethylene glycol)–poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions. PMID:23631539

Test of Antifibrotic Drugs in a Cellular Model of Fibrosis Based on Muscle-Derived Fibroblasts from Duchenne Muscular Dystrophy Patients.

PubMed

Zanotti, Simona; Mora, Marina

2018-01-01

An in vitro model of muscle fibrosis, based on the use of primary human fibroblasts isolated from muscle biopsies of patients affected by Duchenne muscular dystrophies (DMD) and cultivated in monolayer and 3D conditions, is used to test the potential antifibrotic activity of pirfenidone (PFD). This in vitro model may be usefully also to evaluate the toxicity and efficacy of other candidate molecules for the treatment of fibrosis. The drug toxicity is evaluated using a colorimetric assay based on the conversion of tetrazolium salt (MTT) to insoluble formazan, while the effect of the drug on cell proliferation is measured with the bromodeoxyuridine incorporation assay. The efficacy of the drug is evaluated in fibroblast monolayers by quantitating synthesis and deposition of intracellular collagen with a spectrophotometric picrosirius red-based assay, and by quantitating cell migration using a "scratch" assay. The efficacy of PFD as antifibrotic drug is also evaluated in a 3D fibroblast model by measuring diameters and number of nodules.

21 CFR 207.22 - How and where to register and list drugs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... request from the Records Repository Team (HFD-143), Center for Drug Evaluation and Research, Food and Drug... 21 Food and Drugs 4 2010-04-01 2010-04-01 false How and where to register and list drugs. 207.22 Section 207.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

The evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 as a drug and as drug carriers: a systematic review and meta-analysis.

PubMed

Jędrych, Marian; Borowska, Katarzyna; Galus, Ryszard; Jodłowska-Jędrych, Barbara

2014-02-28

The purpose of this study was to investigate the evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 (PAMAM G4) as a drug and as drug carriers by a systematic review of literature and meta-analysis. The results obtained from meta-analysis concluded that drug therapy reduces the change of parameters in relation to the control. The impact of the drug administered to change the test parameters are dependent on the type of tissue. PAMAM G4 may be effective in vitro and in vivo as a drug and drug carriers and may have appropriate applications in various fields of medicine. PAMAM G4 dendrimers hold promises for nanomedicine. Copyright © 2013 Elsevier B.V. All rights reserved.

21 CFR 312.48 - Dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... division in FDA's Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research which is responsible for review of the IND, beginning with the consumer safety officer assigned to the... director of the division in FDA's Center for Drug Evaluation and Research or Center for Biologics...

21 CFR 601.12 - Changes to an approved application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... qualitative or quantitative formulation, including inactive ingredients, or in the specifications provided in... Evaluation and Research or the Director, Center for Drug Evaluation and Research, may approve a written... promotional labeling shall be submitted to the Center for Biologics Evaluation and Research or Center for Drug...

21 CFR 601.12 - Changes to an approved application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... qualitative or quantitative formulation, including inactive ingredients, or in the specifications provided in... Evaluation and Research or the Director, Center for Drug Evaluation and Research, may approve a written... promotional labeling shall be submitted to the Center for Biologics Evaluation and Research or Center for Drug...

21 CFR 601.12 - Changes to an approved application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... qualitative or quantitative formulation, including inactive ingredients, or in the specifications provided in... Evaluation and Research or the Director, Center for Drug Evaluation and Research, may approve a written... promotional labeling shall be submitted to the Center for Biologics Evaluation and Research or Center for Drug...

21 CFR 601.12 - Changes to an approved application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... qualitative or quantitative formulation, including inactive ingredients, or in the specifications provided in... Evaluation and Research or the Director, Center for Drug Evaluation and Research, may approve a written... promotional labeling shall be submitted to the Center for Biologics Evaluation and Research or Center for Drug...

21 CFR 601.12 - Changes to an approved application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... qualitative or quantitative formulation, including inactive ingredients, or in the specifications provided in... Evaluation and Research or the Director, Center for Drug Evaluation and Research, may approve a written... promotional labeling shall be submitted to the Center for Biologics Evaluation and Research or Center for Drug...

Combination products regulation at the FDA.

PubMed

Lauritsen, K J; Nguyen, T

2009-05-01

The US Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, efficacy, and security of drugs, biological products, and medical devices. As single-entity products, drugs are generally regulated by the Center for Drug Evaluation and Research (CDER), devices by the Center for Devices and Radiological Health (CDRH), and biologics by the Center for Biologics Evaluation and Research (CBER). In recent years, technological advances have led to a blurring of the historical lines of separation between the centers.

[Categories and characteristics of BPH drug evaluation models: a comparative study].

PubMed

Huang, Dong-Yan; Wu, Jian-Hui; Sun, Zu-Yue

2014-02-01

Benign prostatic hyperplasia (BPH) is a worldwide common disease in men over 50 years old, and the exact cause of BPH remains largely unknown. In order to elucidate its pathogenesis and screen effective drugs for the treatment of BPH, many BPH models have been developed at home and abroad. This article presents a comprehensive analysis of the categories and characteristics of BPH drug evaluation models, highlighting the application value of each model, to provide a theoretical basis for the development of BPH drugs.

Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

NASA Astrophysics Data System (ADS)

Chakkarapani, Prabu; Subbiah, Latha; Palanisamy, Selvamani; Bibiana, Arputha; Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer

2015-04-01

We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO3-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO3-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 μm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy.

Establishment of an evaluation method to detect drug distribution in hair follicles.

PubMed

Abe, Akinari; Saito, Miyuki; Kadhum, Wesam R; Todo, Hiroaki; Sugibayashi, Kenji

2018-05-05

Development of an appropriate method to evaluate drug disposition or targeting ability in hair follicles (HFs) is urgently needed in order to develop useful pharmaceutical products with pharmacological effects in HFs. In the present study, a cyanoacrylate biopsy (CB) method was used to measure drug disposition in HFs using a model hydrophilic drug, caffeine (CAF), and a lipophilic drug, 4-butylresorcinol (BR), in excised porcine skin. As a result, the height of HF replicas and the recovery ratio decreased with an increase in the application times of the CB method. HF replicas with a length of approximately 175 µm were obtained using a single application of the CB method. Drug distribution in the HF was detected even 5 min after topical application regardless of the lipophilicity of the drugs, although no drug disposition was observed in the deeper layers of the stratum corneum at the same time (5 min). Furthermore, significantly higher amounts of BR were observed in the stratum corneum and HF, compared with those of CAF. These results suggested that the CB method could be useful to evaluate the safety and efficacy as well as the disposition of topically applied chemicals, especially for HF-targeting drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Optimization of drug loading to improve physical stability of paclitaxel-loaded long-circulating liposomes.

PubMed

Kannan, Vinayagam; Balabathula, Pavan; Divi, Murali K; Thoma, Laura A; Wood, George C

2015-01-01

The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.

76 FR 79701 - Bristol-Myers Squibb Co. et al.; Withdrawal of Approval of 70 New Drug Applications and 97...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

...: Florine Purdie, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0411... Drug Applications; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction...

76 FR 64951 - Apothecon et al.; Withdrawal of Approval of 103 New Drug Applications and 35 Abbreviated New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... INFORMATION CONTACT: Florine Purdie, Center for Drug Evaluation and Research, Food and Drug Administration... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0026... Applications; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The...

99 Films on Drugs.

ERIC Educational Resources Information Center

Weber, David O., Ed.

This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations

PubMed Central

Thiel, Christoph; Cordes, Henrik; Fabbri, Lorenzo; Aschmann, Hélène Eloise; Baier, Vanessa; Atkinson, Francis; Blank, Lars Mathias; Kuepfer, Lars

2017-01-01

Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes of genes, and individual genes. The identified subsets of drugs were next analyzed with regard to drug-related characteristics and their physicochemical properties. Toxic changes were finally evaluated to predict both molecular biomarkers and potential drug-drug interactions. The results may facilitate the early diagnosis of adverse drug events in clinical application. PMID:28151932

Precursor medications as a source of methamphetamine and/or amphetamine positive drug testing results.

PubMed

Cody, John T

2002-05-01

Medical Review Officer interpretation of laboratory results is an important component of drug testing programs. The clinical evaluation of laboratory results to assess the possibility of appropriate medical use of a drug is a task with many different facets, depending on the drug class considered. This intercession prevents the reporting of positive results unless it is apparent that drugs were used illicitly. In addition to the commonly encountered prescribed drugs that yield positive drug testing results, other sources of positive results must be considered. This review describes a series of compounds referred to as "precursor" drugs that are metabolized by the body to amphetamine and/or methamphetamine. These compounds lead to positive results for amphetamines even though neither amphetamine nor methamphetamine were used, a possibility that must be considered in the review of laboratory results. Description of the drugs, their clinical indications, and results seen following administration are provided. This information allows for the informed evaluation of results with regard to the potential involvement of these drugs.

Legal requirements for drug testing in children in Germany.

PubMed

Hasskarl, H

1983-01-01

Since 1966 the problem of evaluation of drugs for use in man has increasingly become the subject of both international and national consideration. It was generally felt, that there is a need for a special protection for children being the subjects of the clinical evaluation of drugs. A new impulse with regard to the protection of children was recently set by the Council for International Organizations of Medical Sciences. German legislation has included these international convictions and recommendations pertaining to the performance of clinical trials. Articles 40 and 41 of the German Drug Law of 1976 are an emanation of WHO principles as well as of the Declaration of Helsinki. These articles include special provisions for the protection of children as volunteers of clinical trials, because clinical trials in children are indispensable for research on diseases of children. It is laid down in the Law that children should never be subject of research that might equally well be carried out on adults. The willing cooperation and, as far as feasible, consent of the child and its custodians has to be sought. The German Law provides that trials in healthy children may take place only with regard to diagnostic and prophylactic drugs, not with regard to the therapeutics. Article 41 of the German Drug Law permits the clinical evaluation of drugs in ill children. Therapeutic drugs may, however, be tested in children only under the condition that the drug is determined to cure the special disease under which the child is suffering. Special aspects of the clinical evaluation of drugs in children, not contained in the law, need further discussion and clarification.

Study of small-cell lung cancer cell-based sensor and its applications in chemotherapy effects rapid evaluation for anticancer drugs.

PubMed

Guohua, Hui; Hongyang, Lu; Zhiming, Jiang; Danhua, Zhu; Haifang, Wan

2017-11-15

Small cell lung cancer (SCLC) is a smoking-related cancer disease. Despite improvement in clinical survival, SCLC outcome remains extremely poor. Cisplatin (DDP) is the first-line chemotherapy drug for SCLC, but the choice of second-line chemotherapy drugs is not clear. In this paper, a SCLC cell-based sensor was proposed, and its applications in chemotherapy effects rapid evaluation for anticancer drugs were investigated. SCLC cell lines lung adenocarcinoma cell (LTEP-P) and DDP-resistant lung adenocarcinoma cell (LTEP-P/DDP-1.0) are cultured on carbon screen-printed electrode (CSPE) to fabricate integrated cell-based sensor. Several chemotherapy anticancer drugs, including cisplatin, ifosmamide, gemcitabine, paclitaxel, docetaxel, vinorelbine, etoposide, camptothecin, and topotecan, are selected as experimental chemicals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests are conducted to evaluate chemotherapy drug effects on LTEP-P and LTEP-P/DDP-1.0 cell lines. Electrical cell-substrate impedance sensing (ECIS) responses to anti-tumor chemicals are measured and processed by double-layered cascaded stochastic resonance (DCSR). Cisplatin solutions in different concentrations measurement results demonstrate that LTEP-P cell-based sensor presents quantitative analysis abilities for cisplatin and topotecan. Cisplatin and its mixtures can also be discriminated. Results demonstrate that LTEP-P cell-based sensor sensitively evaluates chemotherapy drugs' apoptosis function to SCLC cells. LTEP-P/DDP-1.0 cell-based sensor responses demonstrate that gemcitabine, vinorelbine, and camptothecin are ideal second-line drugs for clinical post-cisplatin therapy than other drugs according to MTT test results. This work provides a novel way for SCLC second-line clinical chemotherapy drug screening. Copyright © 2017 Elsevier B.V. All rights reserved.

Food and Drug Administration Evaluation and Cigarette Smoking Risk Perceptions

ERIC Educational Resources Information Center

Kaufman, Annette R.; Waters, Erika A.; Parascandola, Mark; Augustson, Erik M.; Bansal-Travers, Maansi; Hyland, Andrew; Cummings, K. Michael

2011-01-01

Objectives: To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…

21 CFR 822.8 - When, where, and how must I submit my postmarket surveillance plan?

Code of Federal Regulations, 2010 CFR

2010-04-01

... submission to the Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and... Document Room, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd... 21 Food and Drugs 8 2010-04-01 2010-04-01 false When, where, and how must I submit my postmarket...

Local Evaluation of Programs Funded under the Drug-Free Schools and Communities Act. Final Report.

ERIC Educational Resources Information Center

Tashjian, Michael D.; Elliott, Barbara

In September 1993 the U.S. Department of Education (ED) released a handbook to assist school- and community-based practitioners in designing and conducting evaluations of drug- and violence-prevention programs funded under the Drug Free Schools and Communities Act (DFSCA). A study was undertaken to assess the level of customer satisfaction with…

Evaluation of the Discover Drug Education Curriculum for Grades K-4.

ERIC Educational Resources Information Center

Adams, Ronald D.; Butler, Joan M.

A major purpose of this study was to establish and test a procedure for evaluating drug education curricula that allows for a more objective view of the effectiveness of drug education materials and the instructional delivery system. A major focus of the study was to determine the extent to which the Discover Curriculum affected student outcomes.…

Evaluation of internet websites marketing herbal weight-loss supplements to consumers.

PubMed

Jordan, Melanie A; Haywood, Tasha

2007-11-01

The aim of this study was to evaluate the quality and quantity of drug information available to consumers on Internet websites marketing herbal weight-loss dietary supplements in the United States. We conducted an Internet search using the search engines Yahoo and Google and the keywords "herbal weight loss." Website content was evaluated for the presence of active/inactive ingredient names and strengths and other Food and Drug Administration (FDA) labeling requirements. Information related to drug safety for the most common herbal ingredients in the products evaluated was compared against standard herbal drug information references. Thirty-two (32) websites were evaluated for labeling requirements and safety information. All sites listed an FDA disclaimer statement and most sites (84.4%) listed active ingredients, although few listed strengths or inactive ingredients. Based on the drug information for the most common ingredients found in the weight-loss dietary supplements evaluated, potential contraindications for cardiovascular conditions, pregnancy/nursing, and high blood pressure were listed most frequently (73%, 65.5%, and 37%, respectively), whereas few websites listed potential drug interactions or adverse reactions. Potential hazards posed by dietary supplements may not be accurately, if at all, represented on Internet websites selling these products. Since consumers may not approach their physicians or pharmacists for information regarding use of dietary supplements in weight loss, it becomes necessary for health care providers to actively engage their patients in open discussion regarding the use, benefits, and hazards of dietary supplements.

Drug safety data mining with a tree-based scan statistic.

PubMed

Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

2013-05-01

In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

PubMed

Košir, Darjan; Ojsteršek, Tadej; Vrečer, Franc

2018-06-14

Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.

Maternal drug use: evaluation of risks to breast-fed infants.

PubMed

Kirksey, A; Groziak, S M

1984-01-01

This paper, based on a review of the literature, evaluates the risks to infants of maternal drug use during lactation. The potential harm of a particular drug to the breastfed infant is related both to the complex mechanism of milk synthesis and secretion and the mode of passage of the drug from plasma into milk. The 1st part of the paper discusses mammary cell and milk synthesis, milk secretion and composition, the mode of passage of drugs into milk, and factors influencing drug concentrations in milk. Drug concentrations in milk are dependent on 6 major factors: drug dosage, proportion bound in plasma, molecular weight, lipid solubility, degree of ionization, and pH difference between plasma and milk. Drugs that are weak acids are ionized to a greater extent and are more protein-bound than weak alkaline drugs. The 2nd part of the paper evaluates the risks to breastfed infants of selected pharmacons. Some categories of drugs that contain pharmacons that should be limited or avoided by nursing mothers are alkylating agents, analgesics and anti-inflammatory agents, anticoagulants, anticonvulsants, anti-infective agents, central nervous system stimulants, hormones, laxatives, minerals, provitamins, psychotherapeutic agents, thyroid affecting agents, and vitamins. The following precautions are suggested to minimize the risks of potentially harmful pharmacons: 1) all unnecessary medications should be avoided by nrusing mothers; 2) if medication is necessary during lactation, drug dosage should be controlled and the infant should be monitored for adverse symptoms; 3) drugs should be administered shortly after breastfeeding and the interval prolonged before the next feeding; and 4) if the infant must be fed soon after a potentially harmful drug has been taken by the mother, bottle feeding is recommended.

21 CFR 312.310 - Individual patients, including for emergency use.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... 312.310 Section 312.310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Expanded Access to... communications. For investigational biological drug products regulated by the Center for Biologics Evaluation and...

Analysis of chats on French internet forums about drugs and pregnancy.

PubMed

Palosse-Cantaloube, Lucie; Lacroix, Isabelle; Rousseau, Vanessa; Bagheri, Haleh; Montastruc, Jean-Louis; Damase-Michel, Christine

2014-12-01

Some pregnant women use the internet to search for medical information. However, online information is not controlled. The objectives were to describe French online chats about drugs and pregnancy and evaluate the quality and reliability of information shared by internet users. This French descriptive study was performed in November 2012. In order to identify drugs and pregnancy-related forum websites, we used three French key words: forum, pregnancy and drug. We explored the first 10 websites from the search result. Diseases were described using the International Classification of Diseases and drugs classified with the Anatomical Therapeutic Chemical codes and the FDA risk classification. We selected 115 questions that were mainly posted by pregnant internet users in French forums. Drugs raising questions were mostly "nervous system," "anti-infective for systemic use" and "respiratory system" drugs. The risk during pregnancy for nearly half of these drugs had not been evaluated properly. Health professionals were only involved in 7% of the 214 answers. Internet users advised to take a drug in 21% of their answers. Thirty-four percent of those recommended drugs had not been well-evaluated or were potentially at risk during pregnancy. Finally, 12% of the answers could be at risk for pregnant woman. This study shows that information related to drugs and pregnancy in online chats could be at risk for pregnant women. Internet users must be aware that online forums are not reliable sources of information. Copyright © 2014 John Wiley & Sons, Ltd.

The discovery of drug-induced illness.

PubMed

Jick, H

1977-03-03

The increased use of drugs (and the concurrent increased risks of drug-induced illness) require definition of relevant research areas and strategy. For established marketed drugs, research needs depend on the magnitudes of risk of an illness from a drug and the base-line risk. With the drug risk high and the base-line risk low, the problem surfaces in premarketing studies or through the epidemic that develops after marketing. If the drug adds slightly to a high base-line risk, the effect is undetectable. When both risks are low, adverse effects can be discovered by chance, but systematic case-referent studies can speed discovery. If both risks are high, clinical trials and nonexperimental studies may be used. With both risks intermediate, systematic evaluations, especially case-referent studies are needed. Newly marketed drugs should be routinely evaluated through compulsory registration and follow-up study of the earliest users.

Consumer perceptions of prescription drug websites: a pilot study.

PubMed

Wymer, Walter

2010-04-01

Consumer perceptions of the information content contained on prescription drug websites was of interest in this investigation. Twenty branded prescription drugs were selected because they were evaluated as being poor consumer choices for safety reasons or because better alternatives existed. Study participants visited each of 20 websites for the selected drugs, and then they answered a series of questions for each website, in order to evaluate each website's information content. Participants, without knowing the selected prescription drugs were selected because they were problematic, reported that the drug company information was complete, fully presenting benefit and risk information, without being false or misleading in any respect. Pricing information was generally not provided by drug companies. Alternative medicines, treatments, and behavioral approaches for dealing with an illness or health condition were generally not part of the information provided by drug companies. Public policy implications are also discussed.

Assessment of Methodological Quality of Economic Evaluations in Belgian Drug Reimbursement Applications

PubMed Central

Simoens, Steven

2013-01-01

Objectives This paper aims to assess the methodological quality of economic evaluations included in Belgian reimbursement applications for Class 1 drugs. Materials and Methods For 19 reimbursement applications submitted during 2011 and Spring 2012, a descriptive analysis assessed the methodological quality of the economic evaluation, evaluated the assessment of that economic evaluation by the Drug Reimbursement Committee and the response to that assessment by the company. Compliance with methodological guidelines issued by the Belgian Healthcare Knowledge Centre was assessed using a detailed checklist of 23 methodological items. The rate of compliance was calculated based on the number of economic evaluations for which the item was applicable. Results Economic evaluations tended to comply with guidelines regarding perspective, target population, subgroup analyses, comparator, use of comparative clinical data and final outcome measures, calculation of costs, incremental analysis, discounting and time horizon. However, more attention needs to be paid to the description of limitations of indirect comparisons, the choice of an appropriate analytic technique, the expression of unit costs in values for the current year, the estimation and valuation of outcomes, the presentation of results of sensitivity analyses, and testing the face validity of model inputs and outputs. Also, a large variation was observed in the scope and depth of the quality assessment by the Drug Reimbursement Committee. Conclusions Although general guidelines exist, pharmaceutical companies and the Drug Reimbursement Committee would benefit from the existence of a more detailed checklist of methodological items that need to be reported in an economic evaluation. PMID:24386474

Assessment of methodological quality of economic evaluations in belgian drug reimbursement applications.

PubMed

Simoens, Steven

2013-01-01

This paper aims to assess the methodological quality of economic evaluations included in Belgian reimbursement applications for Class 1 drugs. For 19 reimbursement applications submitted during 2011 and Spring 2012, a descriptive analysis assessed the methodological quality of the economic evaluation, evaluated the assessment of that economic evaluation by the Drug Reimbursement Committee and the response to that assessment by the company. Compliance with methodological guidelines issued by the Belgian Healthcare Knowledge Centre was assessed using a detailed checklist of 23 methodological items. The rate of compliance was calculated based on the number of economic evaluations for which the item was applicable. Economic evaluations tended to comply with guidelines regarding perspective, target population, subgroup analyses, comparator, use of comparative clinical data and final outcome measures, calculation of costs, incremental analysis, discounting and time horizon. However, more attention needs to be paid to the description of limitations of indirect comparisons, the choice of an appropriate analytic technique, the expression of unit costs in values for the current year, the estimation and valuation of outcomes, the presentation of results of sensitivity analyses, and testing the face validity of model inputs and outputs. Also, a large variation was observed in the scope and depth of the quality assessment by the Drug Reimbursement Committee. Although general guidelines exist, pharmaceutical companies and the Drug Reimbursement Committee would benefit from the existence of a more detailed checklist of methodological items that need to be reported in an economic evaluation.

Mid-Term Assessment of the EU Drugs Strategy 2013-2020 and Final Evaluation of the Action Plan on Drugs 2013-2016: Final report.

PubMed

Emilie, Balbirnie; Matthew, Davies; Emma, Disley; Cristina Gonzalez, Monsalve; Stephen, Hartka; Stijn, Hoorens; Kristy, Kruithof; Martin, Sacher; Jirka, Taylor

2018-01-01

The aim of the EU Drugs Strategy 2013-2020 is to contribute to a reduction in drug demand and drug supply within the EU. The Strategy has so far been implemented by an Action Plan covering the period 2013-2016. This article sets out the findings of an evaluation that assesses the degree of implementation of the Strategy and the Action Plan in terms of outputs and, where possible, impacts. It looks at the extent to which the objectives of the Strategy have been achieved. The evaluation aims to provide evidence to support the European Commission's decision about whether to propose a new Action Plan for the period 2017-2020 and, if so, what changes would be needed compared to the current plan. Through applying a mixed-methods approach, the evaluation examined the effectiveness, efficiency, relevance and coherence of the actions undertaken on the basis of the EU Drugs Strategy and the Action Plan, as well as their EU added value. The evaluation makes 20 recommendations, addressed to the European Commission, Member States, the European Council and other stakeholders. The key recommendation for the Commission is that a new Action Plan should be implemented for the period 2017-2020. This should be an updated version of the current Action Plan, rather than taking a new approach or introducing more new actions.

Formulation and optimization of coated PLGA – Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency

PubMed Central

Peter Christoper, G.V.; Vijaya Raghavan, C.; Siddharth, K.; Siva Selva Kumar, M.; Hari Prasad, R.

2013-01-01

In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 23 factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28–57%, process yield of 60–76% was achieved and drug release for the formulations were in the range of 50–85%. The drug release from the formulations was found to follow Higuchi release pattern, n–value obtained after Korsemeyer plot was in the range of 0.56–0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition. PMID:24648825

Clinical Management of HIV Drug Resistance

PubMed Central

Cortez, Karoll J.; Maldarelli, Frank

2011-01-01

Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

Evaluation of the Maximum Allowable Cost Program

PubMed Central

Lee, A. James; Hefner, Dennis; Dobson, Allen; Hardy, Ralph

1983-01-01

This article summarizes an evaluation of the Maximum Allowable Cost (MAC)-Estimated Acquisition Cost (EAC) program, the Federal Government's cost-containment program for prescription drugs.1 The MAC-EAC regulations which became effective on August 26, 1976, have four major components: (1) Maximum Allowable Cost reimbursement limits for selected multisource or generically available drugs; (2) Estimated Acquisition Cost reimbursement limits for all drugs; (3) “usual and customary” reimbursement limits for all drugs; and (4) a directive that professional fee studies be performed by each State. The study examines the benefits and costs of the MAC reimbursement limits for 15 dosage forms of five multisource drugs and EAC reimbursement limits for all drugs for five selected States as of 1979. PMID:10309857

75 FR 37818 - Issues in the Design and Conduct of Clinical Trials for Antibacterial Drug Development; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-30

... Moser or Lori Benner, Center for Drug Evaluation and Research, Food and Drug Administration, Office of... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001... AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food and Drug...

When Is It Important to Measure Unbound Drug in Evaluating Nanomedicine Pharmacokinetics?

PubMed Central

Stern, Stephan T.; Stevens, David M.

2016-01-01

Nanoformulations have become important tools for modifying drug disposition, be it from the perspective of enabling prolonged drug release, protecting the drug molecule from metabolism, or achieving targeted delivery. When examining the in vivo pharmacokinetic properties of these formulations, most investigations either focus on systemic concentrations of total (encapsulated plus unencapsulated) drug, or concentrations of encapsulated and unencapsulated drug. However, it is rare to find studies that differentiate between protein-bound and unbound (free) forms of the unencapsulated drug. In light of the unique attributes of these formulations, we cannot simply assume it appropriate to rely upon the protein-binding properties of the traditionally formulated or legacy drug when trying to define the pharmacokinetic or pharmacokinetic/pharmacodynamic characteristics of these nanoformulations. Therefore, this commentary explores reasons why it is important to consider not only unencapsulated drug, but also the portion of unencapsulated drug that is not bound to plasma proteins. Specifically, we highlight those situations when it may be necessary to include measurement of unencapsulated, unbound drug concentrations as part of the nanoformulation pharmacokinetic evaluation. PMID:27670412

In vitro and in vivo investigation of taste-masking effectiveness of Eudragit E PO as drug particle coating agent in orally disintegrating tablets.

PubMed

Drašković, Milica; Medarević, Djordje; Aleksić, Ivana; Parojčić, Jelena

2017-05-01

Considering that bitter taste of drugs incorporated in orally disintegrating tablets (ODTs) can be the main reason for avoiding drug therapy, it is of the utmost importance to achieve successful taste-masking. The evaluation of taste-masking effectiveness is still a major challenge. The objective of this study was to mask bitter taste of the selected model drugs by drug particle coating with Eudragit ® E PO, as well as to evaluate taste-masking effectiveness of prepared ODTs using compendial dissolution testing, dissolution in the small-volume shake-flask assembly and trained human taste panel. Model drugs were coated in fluidized bed. Disintequik™ ODT was used as a novel co-processed excipient for ODT preparation. Selected formulations were investigated in vitro and in vivo using techniques for taste-masking assessment. Significantly slower drug dissolution was observed from tablets with coated drug particles during the first 3 min of investigation. Results of in vivo taste-masking assessment demonstrated significant improvement in drug bitterness suppression in formulations with coated drug. Strong correlation between the results of drug dissolution in the small-volume shake-flask assembly and in vivo evaluation data was established (R ≥ 0.970). Drug particle coating with Eudragit ® E PO can be a suitable approach for bitter taste-masking. Strong correlation between in vivo and in vitro results implicate that small-volume dissolution method may be used as surrogate for human panel taste-masking assessment, in the case of physical taste-masking approach application.

Impact of the pan-Canadian Oncology Drug Review on provincial concordance with respect to cancer drug funding decisions and time to funding.

PubMed

Srikanthan, A; Mai, H; Penner, N; Amir, E; Laupacis, A; Sabharwal, M; Chan, K K W

2017-10-01

The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 to address uneven drug coverage and lack of transparency with respect to the various provincial cancer drug review processes in Canada. We evaluated the impact of the pcodr on provincial decision concordance and time from Notice of Compliance (noc) to drug funding. In a retrospective review, Health Canada's Drug Product Database was used to identify new indications for cancer drugs between January 2003 and May 2014, and provincial formulary listings for drug-funding dates and decisions between 1 January 2003 and 31 December 2014 were retrieved. Multiple linear models and quantile regressions were used to evaluate changes in time to decision-making before and after the implementation of the pcodr. Agreement of decisions between provinces was evaluated using kappa statistics. Data were available from 9 provinces (all Canadian provinces except Quebec), identifying 88 indications that represented 51 unique cancer drugs. Two provinces lacked available data for all 88 indications at the time of data collection. Interprovincial concordance in drug funding decisions significantly increased after the pcodr's implementation (Brennan-Prediger coefficient: 0.54 pre-pcodr vs. 0.78 post-pcodr; p = 0.002). Nationwide, the median number of days from Health Canada's noc date to the date of funding significantly declined (to 393 days from 522 days, p < 0.001). Exploratory analyses excluding provinces with incomplete data did not change the results. After the implementation of the pcodr, greater concordance in cancer drug funding decisions between provinces and decreased time to funding decisions were observed.

ONDCP Media Campaign: Contractor's National Evaluation Did Not Find That the Youth Anti-Drug Media Campaign Was Effective in Reducing Youth Drug Use. Report to the Subcommittee on Transportation, Treasury, the Judiciary, Housing and Urban Development, and Related Agencies, Committee on Appropriations, U.S. Senate. GAO-06-818

ERIC Educational Resources Information Center

Kingsbury, Nancy; Ekstrand, Laurie E.

2006-01-01

GAO's review of Westat's evaluation reports and associated documentation leads to the conclusion that the evaluation provides credible evidence that the campaign was not effective in reducing youth drug use, either during the entire period of the campaign or during the period from 2002 to 2004 when the campaign was redirected and focused on…

Chemotherapy of Rodent Malaria. Evaluation of Drug Action against Normal and Resistant Strains including Exo-Erythrocytic Stages.

DTIC Science & Technology

1979-10-01

AD-RI35 058 CHEMOTHERAPY’OF RODENT MALARIA EVALUATION OF DRUG I/i ACTION AGAINST NORMAL R-.(U) LIVERPOQL SCHOOL OF TROPICAL MEDICINE ENGLAND) DEPT OF...PARS N PETERSUNCLASSIFIED OCT 79 DANDi?79 6 -G94 57 F/ 6 6 /15117EhEEohEohhhiE *flfl 4L 2 Q~ -8 hi 36 11125 LA 11.6 MICROCOPY RESOLUTION TEST CHART...NATIONAL BUREAU OF STANDARDS- 1963-A I" CHEMOTHERAPY RODENT MALARIA EVALUATION OF DRUG AC ON AGAINST NORMAL AND RESISTANT STRAINS INCLUDING EXO

The Two Faces of Social Interaction Reward in Animal Models of Drug Dependence

PubMed Central

Rawas, Rana El

2016-01-01

Drug dependence is a serious health and social problem. Social factors can modify vulnerability to developing drug dependence, acting as risk factors or protective factors. Whereas stress and peer environment that encourage substance use may increase drug taking, strong attachments between family members and peer environment that do not experience drug use may protect against drug taking and, ultimately, drug dependence. The rewarding effects of drug abuse and social interaction can be evaluated using animal models. In this review we focus on evaluating social interaction reward in the conditioned place preference paradigm. We give an overview of how social interaction, if made available within the drug context, may facilitate, promote and interact with the drug’s effects. However, social interaction, if offered alternatively outside the drug context, may have pronounced protective effects against drug abuse and relapse. We also address the importance of the weight difference parameter between the social partners in determining the positive or “agonistic” versus the hostile or “antagonistic” social interaction. We conclude that understanding social interaction reward and its subsequent effects on drug reward is sorely needed for therapeutic interventions against drug dependence. PMID:26088685

21 CFR 860.123 - Reclassification petition: Content and form.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Reclassification petition: Content and form. 860.123 Section 860.123 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

32 CFR 634.13 - Alcohol and drug abuse programs.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 4 2012-07-01 2011-07-01 true Alcohol and drug abuse programs. 634.13 Section... and drug abuse programs. (a) Commanders will refer military personnel suspected of drug or alcohol abuse for evaluation in the following circumstances: (1) Behavior indicative of alcohol or drug abuse...

32 CFR 634.13 - Alcohol and drug abuse programs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Alcohol and drug abuse programs. 634.13 Section... and drug abuse programs. (a) Commanders will refer military personnel suspected of drug or alcohol abuse for evaluation in the following circumstances: (1) Behavior indicative of alcohol or drug abuse...

32 CFR 634.13 - Alcohol and drug abuse programs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 4 2014-07-01 2013-07-01 true Alcohol and drug abuse programs. 634.13 Section... and drug abuse programs. (a) Commanders will refer military personnel suspected of drug or alcohol abuse for evaluation in the following circumstances: (1) Behavior indicative of alcohol or drug abuse...

32 CFR 634.13 - Alcohol and drug abuse programs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 4 2013-07-01 2013-07-01 false Alcohol and drug abuse programs. 634.13 Section... and drug abuse programs. (a) Commanders will refer military personnel suspected of drug or alcohol abuse for evaluation in the following circumstances: (1) Behavior indicative of alcohol or drug abuse...

32 CFR 634.13 - Alcohol and drug abuse programs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Alcohol and drug abuse programs. 634.13 Section... and drug abuse programs. (a) Commanders will refer military personnel suspected of drug or alcohol abuse for evaluation in the following circumstances: (1) Behavior indicative of alcohol or drug abuse...

77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... INFORMATION CONTACT: Astrid Lopez-Goldberg, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563] Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration and...

A Prescription for Drug Formulary Evaluation: An Application of Price Indexes

PubMed Central

Glazer, Jacob; Huskamp, Haiden A.; McGuire, Thomas G.

2012-01-01

Existing economic approaches to the design and evaluation of health insurance do not readily apply to coverage decisions in the multi-tiered drug formularies characterizing drug coverage in private health insurance and Medicare. This paper proposes a method for evaluating a change in the value of a formulary to covered members based on the economic theory of price indexes. A formulary is cast as a set of demand-side prices, and our measure approximates the compensation (positive or negative) that would need to be paid to consumers to accept the new set of prices. The measure also incorporates any effect of the formulary change on plan drug acquisition costs and “offset effects” on non-drug services covered by the plan. Data needed to calculate formulary value are known or can be forecast by a health plan. We illustrate the method with data from a move from a two- to a three-tier formulary. PMID:23372543

21 CFR 70.42 - Criteria for evaluating the safety of color additives.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Criteria for evaluating the safety of color... listed color additive will be safe for its intended use or uses in or on food, drugs, or cosmetics. The Commissioner may list a color additive for use generally in or on food, in or on drugs, or in or on cosmetics...

21 CFR 70.42 - Criteria for evaluating the safety of color additives.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Criteria for evaluating the safety of color... listed color additive will be safe for its intended use or uses in or on food, drugs, or cosmetics. The Commissioner may list a color additive for use generally in or on food, in or on drugs, or in or on cosmetics...

21 CFR 70.42 - Criteria for evaluating the safety of color additives.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Criteria for evaluating the safety of color... listed color additive will be safe for its intended use or uses in or on food, drugs, or cosmetics. The Commissioner may list a color additive for use generally in or on food, in or on drugs, or in or on cosmetics...

21 CFR 70.42 - Criteria for evaluating the safety of color additives.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Criteria for evaluating the safety of color... listed color additive will be safe for its intended use or uses in or on food, drugs, or cosmetics. The Commissioner may list a color additive for use generally in or on food, in or on drugs, or in or on cosmetics...

The Convergent and Divergent Validity of the Matson Evaluation of Drug Side-Effects (MEDS) and the Dyskinesia Identification System: Condensed User Scale (DISCUS)

ERIC Educational Resources Information Center

Matson, Johnny L.; Fodstad, Jill C.; Rivet, Tessa T.

2008-01-01

Background: Medication side-effects such as tardive dyskinesia (TD) are known to occur in individuals with a history of psychotropic drug use. This study aimed to contribute to the development of measures for assessing TD by examining the validity of the "Matson Evaluation of Drug Side-effects" (MEDS) with the "Dyskinesia…

Training in Evaluation Skills for Drug Treatment and Drug Prevention Professionals in the Commonwealth Caribbean: How Do Non-Governmental and Statutory Services Compare?

ERIC Educational Resources Information Center

Klein, Axel; Day, Marcus

2006-01-01

In the countries of the Commonwealth Caribbean there has been a dramatic expansion in drug demand reduction (DDR) programmes over the past decade. Often drawing on models originating in the countries providing the funding in North America or Europe, these activities have often been inadequately monitored and rarely evaluated. The absence of…

Drug Usage and Attitude Toward Drugs Among College Students

ERIC Educational Resources Information Center

Cross, Herbert J.; Keir, Richard G.

1971-01-01

Results of the data presented suggest that there is considerable experimentation among college students with illegal drugs, especially marijuana. Their attitudes toward other drugs still seems cautious. Marijuana, however, seems-to be accepted and generally positively evaluated. (Author)

Three-dimensional prostate tumor model based on a hyaluronic acid-alginate hydrogel for evaluation of anti-cancer drug efficacy.

PubMed

Tang, Yadong; Huang, Boxin; Dong, Yuqin; Wang, Wenlong; Zheng, Xi; Zhou, Wei; Zhang, Kun; Du, Zhiyun

2017-10-01

In vitro cell-based assays are widely applied to evaluate anti-cancer drug efficacy. However, the conventional approaches are mostly based on two-dimensional (2D) culture systems, making it difficult to recapitulate the in vivo tumor scenario because of spatial limitations. Here, we develop an in vitro three-dimensional (3D) prostate tumor model based on a hyaluronic acid (HA)-alginate hybrid hydrogel to bridge the gap between in vitro and in vivo anticancer drug evaluations. In situ encapsulation of PCa cells was achieved by mixing HA and alginate aqueous solutions in the presence of cells and then crosslinking with calcium ions. Unlike in 2D culture, cells were found to aggregate into spheroids in a 3D matrix. The expression of epithelial to mesenchyme transition (EMT) biomarkers was found to be largely enhanced, indicating an increased invasion and metastasis potential in the hydrogel matrix. A significant up-regulation of proangiogenic growth factors (IL-8, VEGF) and matrix metalloproteinases (MMPs) was observed in 3D-cultured PCa cells. The results of anti-cancer drug evaluation suggested a higher drug tolerance within the 3D tumor model compared to conventional 2D-cultured cells. Finally, we found that the drug effect within the in vitro 3D cancer model based on HA-alginate matrix exhibited better predictability for in vivo drug efficacy.

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

Marks, Louise, E-mail: louise.marks@astrazeneca.com; Borland, Samantha; Philp, Karen

Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil ormore » vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt{sub max} and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability. ► Haemodynamic, contractility, ECG parameters and plasma exposure all measurable. ► Single small animal model offering extensive evaluation of a drug's CV risk. ► Potential to strengthen drug discovery cardiovascular strategy. ► Potential to halt progression of drugs with CV liability, reducing drug attrition.« less

Evaluation of a Peer-Led Drug Abuse Risk Reduction Project for Runaway/Homeless Youths.

ERIC Educational Resources Information Center

Fors, Stuart W.; Jarvis, Sara

1995-01-01

Evaluates the Drug Prevention in Youth risk reduction program that was implemented in shelters for runaway/homeless youths in the southeastern United States. An evaluation strategy was developed allowing for comparisons between peer-led, adult-led and nonintervention groups. Well-trained and motivated peer/near-peer leaders made particularly…

Twenty years of using economic evaluations for drug reimbursement decisions: what has been achieved?

PubMed

Drummond, Michael

2013-12-01

The objective of this article is to examine the impact of economic evaluation on the reimbursement process for pharmaceuticals. The changes in the structure of reimbursement policies necessary to incorporate economic evaluation have been accomplished without major difficulty in most jurisdictions. However, several methodological differences in international guidelines for economic evaluation exist, only some of which can easily be justified. A number of beneficial changes in reimbursement processes have also been observed, such as a trend toward requiring the measurement of more meaningful clinical end points and increased engagement between manufacturers, drug regulators, and payers. A consistent finding in studies of reimbursement decisions is that economic considerations have been influential, second only to the strength of the clinical evidence for the drug of interest. The impact of economic evaluation on the allocation of health care resources is hard to ascertain because little is known about the extent to which reimbursement decisions actually lead to changes in health care practice. However, there is evidence that economic evaluation has assisted price negotiations and enabled reimbursement agencies to target drugs to those patients who will benefit the most.

A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine.

PubMed

Hueza, Isis M; Ponce, Fernando; Garcia, Raphael C T; Marcourakis, Tânia; Yonamine, Maurício; Mantovani, Cínthia de C; Kirsten, Thiago B

2016-01-01

The use of smoked illicit drugs has spread dramatically, but few studies use proper devices to expose animals to inhalational abused drugs despite the availability of numerous smoking devices that mimic tobacco exposure in rodents. Therefore, the present study developed an inexpensive device to easily expose laboratory animals to smoked drugs. We used crack cocaine as the drug of abuse, and the cocaine plasma levels and the behaviors of animals intoxicated with the crack cocaine were evaluated to prove inhaled drug absorption and systemic activity. We developed an acrylic device with two chambers that were interconnected and separated by a hatch. Three doses of crack (100, 250, or 500 mg), which contained 63.7% cocaine, were burned in a pipe, and the rats were exposed to the smoke for 5 or 10 min (n=5/amount/period). Exposure to the 250-mg dose for 10 min achieved cocaine plasma levels that were similar to those of users (170 ng/mL). Behavioral evaluations were also performed to validate the methodology. Rats (n=10/group) for these evaluations were exposed to 250 mg of crack cocaine or air for 10 min, twice daily, for 28 consecutive days. Open-field evaluations were performed at three different periods throughout the experimental design. Exposed animals exhibited transient anorexia, increased motor activity, and shorter stays in central areas of the open field, which suggests reduced anxiety. Therefore, the developed model effectively exposed animals to crack cocaine, and this model may be useful for the investigation of other inhalational abused drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

Getting the cat back in the bag: reforming the way provinces manage drug expenditures to make them manageable.

PubMed

Levy, Adrian R; Gagnon, Yves M

2002-01-01

The fiscal "cat" of healthcare spending - drug expenditures - is out of the bag: drug costs are now the fastest rising component of healthcare expenditures in Canada. Laupacis, Anderson and O'Brien describe the current process of listing drugs on the provincial drug formulary in Ontario, identify factors that may contribute to the rapid growth in drug expenditures, and make a number of recommendations for controlling drug expenditures, including (1) improving the evidence on cost-effectiveness; (2) disseminating the evidence to prescribers; (3) re-evaluating the evidence; and (4) increasing the transparency about the acquisition costs of drugs. These are recommendations that, if implemented, would theoretically help decision-makers make more rational decisions about which drugs to list on provincial formularies. The question of how to implement the recommendations remains to be elucidated, as does an evaluation of the trade-offs between costs and benefits of obtaining better information on cost-effectiveness.

Evaluation of Point-of-Care Resources for Dietary Supplement Information.

PubMed

Montgomery, Ashley E; Beckett, Robert D; Montagano, Kaitlin J; Kutom, Samah

2018-01-01

To evaluate 6 tertiary, point-of-care drug information resources' dietary supplement content. This was a cross-sectional evaluation of Lexicomp Natural Products Database, Micromedex Alternative Medicine, Clinical Pharmacology, Natural Medicines, The Review of Natural Products, and Handbook of Nonprescription Drugs. Each resource was evaluated for scope, completeness, consistency, and ease of use. For a sample of 66 supplements, scope scores ranged from 69.7% (Micromedex) to 100% (Natural Medicines). Completeness scores were high considering uses, dose, adverse effects, and mechanism (85.7% to 100%). Overall completeness scores ranged from 82.5% ( Handbook of Nonprescription Drugs) to 100% (Clinical Pharmacology, Natural Medicines, The Review of Natural Products). Consistency scores ranged from 0% ( Handbook of Nonprescription Drugs) to 100% (Natural Medicines, The Review of Natural Products). Mean time to locate and gather information was similar among groups. Resources were similar for completeness and ease of use. Scope and consistency varied depending on the resource.

DRUG EVALUATION AND DECISION MAKING IN CATALONIA: DEVELOPMENT AND VALIDATION OF A METHODOLOGICAL FRAMEWORK BASED ON MULTI-CRITERIA DECISION ANALYSIS (MCDA) FOR ORPHAN DRUGS.

PubMed

Gilabert-Perramon, Antoni; Torrent-Farnell, Josep; Catalan, Arancha; Prat, Alba; Fontanet, Manel; Puig-Peiró, Ruth; Merino-Montero, Sandra; Khoury, Hanane; Goetghebeur, Mireille M; Badia, Xavier

2017-01-01

The aim of this study was to adapt and assess the value of a Multi-Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of Orphan drugs in Catalonia (Catalan Health Service). The standard evaluation and decision-making procedures of CatSalut were compared with the EVIDEM methodology and contents. The EVIDEM framework was adapted to the Catalan context, focusing on the evaluation of Orphan drugs (PASFTAC program), during a Workshop with sixteen PASFTAC members. The criteria weighting was done using two different techniques (nonhierarchical and hierarchical). Reliability was assessed by re-test. The EVIDEM framework and methodology was found useful and feasible for Orphan drugs evaluation and decision making in Catalonia. All the criteria considered for the development of the CatSalut Technical Reports and decision making were considered in the framework. Nevertheless, the framework could improve the reporting of some of these criteria (i.e., "unmet needs" or "nonmedical costs"). Some Contextual criteria were removed (i.e., "Mandate and scope of healthcare system", "Environmental impact") or adapted ("population priorities and access") for CatSalut purposes. Independently of the weighting technique considered, the most important evaluation criteria identified for orphan drugs were: "disease severity", "unmet needs" and "comparative effectiveness", while the "size of the population" had the lowest relevance for decision making. Test-retest analysis showed weight consistency among techniques, supporting reliability overtime. MCDA (EVIDEM framework) could be a useful tool to complement the current evaluation methods of CatSalut, contributing to standardization and pragmatism, providing a method to tackle ethical dilemmas and facilitating discussions related to decision making.

The impact of cancer drug wastage on economic evaluations.

PubMed

Truong, Judy; Cheung, Matthew C; Mai, Helen; Letargo, Jessa; Chambers, Alexandra; Sabharwal, Mona; Trudeau, Maureen E; Chan, Kelvin K W

2017-09-15

The objective of this study was to determine the impact of modeling cancer drug wastage in economic evaluations because wastage can result from single-dose vials on account of body surface area- or weight-based dosing. Intravenous chemotherapy drugs were identified from the pan-Canadian Oncology Drug Review (pCODR) program as of January 2015. Economic evaluations performed by drug manufacturers and pCODR were reviewed. Cost-effectiveness analyses and budget impact analyses were conducted for no-wastage and maximum-wastage scenarios (ie, the entire unused portion of the vial was discarded at each infusion). Sensitivity analyses were performed for a range of body surface areas and weights. Twelve drugs used for 17 indications were analyzed. Wastage was reported (ie, assumptions were explicit) in 71% of the models and was incorporated into 53% by manufacturers; this resulted in a mean incremental cost-effectiveness ratio increase of 6.1% (range, 1.3%-14.6%). pCODR reported and incorporated wastage for 59% of the models, and this resulted in a mean incremental cost-effectiveness ratio increase of 15.0% (range, 2.6%-48.2%). In the maximum-wastage scenario, there was a mean increase in the incremental cost-effectiveness ratio of 24.0% (range, 0.0%-97.2%), a mean increase in the 3-year total incremental budget costs of 26.0% (range, 0.0%-83.1%), and an increase in the 3-year total incremental drug budget cost of approximately CaD $102 million nationally. Changing the mean body surface area or body weight caused 45% of the drugs to have a change in the vial size and/or quantity, and this resulted in increased drug costs. Cancer drug wastage can increase drug costs but is not uniformly modeled in economic evaluations. Cancer 2017;123:3583-90. © 2017 American Cancer Society. © 2017 American Cancer Society.

Critical review of drug promotional literature using the World Health Organization guidelines

PubMed Central

Ganashree, Puttaswamy; Bhuvana, Krishnaswamy; Sarala, Narayana

2016-01-01

Objective: Drug promotional literatures (DPLs) are used as a promotional tool to advertise new drugs entering the market to doctors. The objective of the present study is to evaluate the accuracy of DPLs by using the World Health Organization (WHO) criteria. Methods: An observational study was conducted from March to August 2014. The DPLs were collected from various departments at R.L. Jalappa Hospital and Research Centre attached to Sri Devaraj Urs Medical College, Kolar, India. The literature was evaluated based on 11 criteria laid down by the WHO. Findings: Two-hundred DPLs were evaluated. Cardiovascular drugs (34 [17%]) were promoted the most, followed by antidiabetic drugs (31 [15.5%]) and antimicrobial agents (29 [14.5%]). Single drug was promoted in 134 (67%) and fixed drug combination in 66 (33%) brochures. Manufacturer's name was mentioned in 194 (97%), but their address was mentioned in 109 (54.5%) claims only. Drug cost was revealed only in 12 (6%) DPLs. Each ingredient's generic name, brand name, and dosage form were mentioned in 197 (98%) brochures. Indication for use was stated in 193 (96.5%) claims. Contraindications, adverse effects, precautions, and drug interactions were listed in 68 (34.5%), 65 (32.5%), 65 (32.5%), and 58 (29%) advertisements. References were cited in 133 (66.5%) brochures. Only 63 (31.5%) literatures had relevant pictures of drugs being promoted and 59 (29.5%) had a graphical representation of pharmacological properties. A total of 131 (69%) DPLs followed 50% of the WHO criteria. Conclusion: Majority of DPLs satisfied only half of the WHO criteria for rational drug promotion and none of them fulfilled all the specified criteria. Incomplete or exaggerated information in DPLs may mislead and result in irrational prescription. Therefore, physicians should critically evaluate DPLs regarding updated scientific evidence required for quality patient care. PMID:27512705

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion.

PubMed

Weersink, Rianne A; Bouma, Margriet; Burger, David M; Drenth, Joost P H; Hunfeld, Nicole G M; Kranenborg, Minke; Monster-Simons, Margje H; van Putten, Sandra A W; Metselaar, Herold J; Taxis, Katja; Borgsteede, Sander D

2016-10-12

Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings. 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/.

GraphSAW: a web-based system for graphical analysis of drug interactions and side effects using pharmaceutical and molecular data.

PubMed

Shoshi, Alban; Hoppe, Tobias; Kormeier, Benjamin; Ogultarhan, Venus; Hofestädt, Ralf

2015-02-28

Adverse drug reactions are one of the most common causes of death in industrialized Western countries. Nowadays, empirical data from clinical studies for the approval and monitoring of drugs and molecular databases is available. The integration of database information is a promising method for providing well-based knowledge to avoid adverse drug reactions. This paper presents our web-based decision support system GraphSAW which analyzes and evaluates drug interactions and side effects based on data from two commercial and two freely available molecular databases. The system is able to analyze single and combined drug-drug interactions, drug-molecule interactions as well as single and cumulative side effects. In addition, it allows exploring associative networks of drugs, molecules, metabolic pathways, and diseases in an intuitive way. The molecular medication analysis includes the capabilities of the upper features. A statistical evaluation of the integrated data and top 20 drugs concerning drug interactions and side effects is performed. The results of the data analysis give an overview of all theoretically possible drug interactions and side effects. The evaluation shows a mismatch between pharmaceutical and molecular databases. The concordance of drug interactions was about 12% and 9% of drug side effects. An application case with prescribed data of 11 patients is presented in order to demonstrate the functionality of the system under real conditions. For each patient at least two interactions occured in every medication and about 8% of total diseases were possibly induced by drug therapy. GraphSAW (http://tunicata.techfak.uni-bielefeld.de/graphsaw/) is meant to be a web-based system for health professionals and researchers. GraphSAW provides comprehensive drug-related knowledge and an improved medication analysis which may support efforts to reduce the risk of medication errors and numerous drastic side effects.

Field evaluation of the Los Angeles Police Department drug detection procedure.

DOT National Transportation Integrated Search

1986-12-01

The Los Angeles Police Department (LAPD) has developed a drug recognition program designed to provide trained officers the ability to detect drug-impaired drivers and to identify the responsible drug class (e.g., stimulant, depressant, etc. ). As par...

Reappraisal and perspectives of clinical drug-drug interaction potential of α-glucosidase inhibitors such as acarbose, voglibose and miglitol in the treatment of type 2 diabetes mellitus.

PubMed

Dash, Ranjeet Prasad; Babu, R Jayachandra; Srinivas, Nuggehally R

2018-01-01

1. Amidst the new strategies being developed for the management of type 2 diabetes mellitus (T2DM) with both established and newer therapies, alpha glucosidase inhibitors (AGIs) have found a place in several treatment protocols. 2. The objectives of the review were: (a) to compile and evaluate the various clinical pharmacokinetic drug interaction data for AGIs such as acarbose, miglitol and voglibose; (b) provide perspectives on the drug interaction data since it encompasses coadministered drugs in several key areas of comorbidity with T2DM. 3. Critical evaluation of the interaction data suggested that the absorption and bioavailability of many coadministered drugs were not meaningfully affected from a clinical perspective. Therefore, on the basis of the current appraisal, none of the AGIs showed an alarming and/or overwhelming trend of interaction potential with several coadministered drugs. Hence, dosage adjustment is not warranted in the use of AGIs in T2DM patients in situations of comorbidity. 4. The newly evolving fixed dose combination strategies with AGIs need to be carefully evaluated to ensure that the absorption and bioavailability of the added drug are not impaired due to concomitant food ingestion.

The importance of employing computational resources for the automation of drug discovery.

PubMed

Rosales-Hernández, Martha Cecilia; Correa-Basurto, José

2015-03-01

The application of computational tools to drug discovery helps researchers to design and evaluate new drugs swiftly with a reduce economic resources. To discover new potential drugs, computational chemistry incorporates automatization for obtaining biological data such as adsorption, distribution, metabolism, excretion and toxicity (ADMET), as well as drug mechanisms of action. This editorial looks at examples of these computational tools, including docking, molecular dynamics simulation, virtual screening, quantum chemistry, quantitative structural activity relationship, principal component analysis and drug screening workflow systems. The authors then provide their perspectives on the importance of these techniques for drug discovery. Computational tools help researchers to design and discover new drugs for the treatment of several human diseases without side effects, thus allowing for the evaluation of millions of compounds with a reduced cost in both time and economic resources. The problem is that operating each program is difficult; one is required to use several programs and understand each of the properties being tested. In the future, it is possible that a single computer and software program will be capable of evaluating the complete properties (mechanisms of action and ADMET properties) of ligands. It is also possible that after submitting one target, this computer-software will be capable of suggesting potential compounds along with ways to synthesize them, and presenting biological models for testing.

Evaluation of five full-text drug databases by pharmacy students, faculty, and librarians: do the groups agree?

PubMed

Kupferberg, Natalie; Jones Hartel, Lynda

2004-01-01

The purpose of this study is to assess the usefulness of five full-text drug databases as evaluated by medical librarians, pharmacy faculty, and pharmacy students at an academic health center. Study findings and recommendations are offered as guidance to librarians responsible for purchasing decisions. Four pharmacy students, four pharmacy faculty members, and four medical librarians answered ten drug information questions using the databases AHFS Drug Information (STAT!Ref); DRUGDEX (Micromedex); eFacts (Drug Facts and Comparisons); Lexi-Drugs Online (Lexi-Comp); and the PDR Electronic Library (Micromedex). Participants noted whether each database contained answers to the questions and evaluated each database on ease of navigation, screen readability, overall satisfaction, and product recommendation. While each study group found that DRUGDEX provided the most direct answers to the ten questions, faculty members gave Lexi-Drugs the highest overall rating. Students favored eFacts. The faculty and students found the PDR least useful. Librarians ranked DRUGDEX the highest and AHFS the lowest. The comments of pharmacy faculty and students show that these groups preferred concise, easy-to-use sources; librarians focused on the comprehensiveness, layout, and supporting references of the databases. This study demonstrates the importance of consulting with primary clientele before purchasing databases. Although there are many online drug databases to consider, present findings offer strong support for eFacts, Lexi-Drugs, and DRUGDEX.

Towards earlier inclusion of Children in Tuberculosis (TB) drugs trials: Consensus statements from an Expert Panel

PubMed Central

Nachman, Sharon; Ahmed, Amina; Amanullah, Farhana; Becerra, Mercedes C; Botgros, Radu; Brigden, Grania; Browning, Renee; Gardiner, Elizabeth; Hafner, Richard; Hesseling, Anneke; How, Cleotilde; Jean-Philippe, Patrick; Lessem, Erica; Makhene, Mamodikoe; Mbelle, Nontombi; Marais, Ben; McIlleron, Helen; Mc Neeley, David F; Mendel, Carl; Murray, Stephen; Navarro, Eileen; Oramasionwu, Gloria E; Porcalla, Ariel R; Powell, Clydette; Powell, Mair; Rigaud, Mona; Rouzier, Vanessa; Samson, Pearl; Schaaf, H. Simon; Shah, Seema; Starke, Jeff; Swaminathan, Soumya; Wobudeya, Eric; Worrell, Carol

2015-01-01

Children represent a significant proportion of the global tuberculosis (TB) burden, and may be disproportionately more affected by its most severe clinical manifestations. Currently available treatments for pediatric drug-susceptible (DS) and drug-resistant (DR) TB, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxicities, and an overall lack of suitable, child-friendly formulations. The complex and burdensome nature of administering the existing regimens to treat DS TB also contributes to the rise of DR TB strains. Despite the availability and use of these therapies for decades, a dearth of dosing evidence in children underscores the importance of sustained efforts for TB drug development to better meet the treatment needs of children with TB. Several new TB drugs and regimens with promising activity against both DS and DR TB strains have recently entered clinical development and are in various phases of clinical evaluation in adults or have received marketing authorization for adults. However, initiation of clinical trials to evaluate these drugs in children is often deferred, pending the availability of complete safety and efficacy data in adults or after drug approval. This document summarizes consensus statements from an international panel of childhood TB opinion leaders which support the initiation of evaluation of new TB drugs and regimens in children at earlier phases of the TB Drug development cycle. PMID:25957923

Evaluation of five full-text drug databases by pharmacy students, faculty, and librarians: do the groups agree?

PubMed Central

Kupferberg, Natalie; Hartel, Lynda Jones

2004-01-01

Objectives: The purpose of this study is to assess the usefulness of five full-text drug databases as evaluated by medical librarians, pharmacy faculty, and pharmacy students at an academic health center. Study findings and recommendations are offered as guidance to librarians responsible for purchasing decisions. Methods: Four pharmacy students, four pharmacy faculty members, and four medical librarians answered ten drug information questions using the databases AHFS Drug Information (STAT!Ref); DRUGDEX (Micromedex); eFacts (Drug Facts and Comparisons); Lexi-Drugs Online (Lexi-Comp); and the PDR Electronic Library (Micromedex). Participants noted whether each database contained answers to the questions and evaluated each database on ease of navigation, screen readability, overall satisfaction, and product recommendation. Results: While each study group found that DRUGDEX provided the most direct answers to the ten questions, faculty members gave Lexi-Drugs the highest overall rating. Students favored eFacts. The faculty and students found the PDR least useful. Librarians ranked DRUGDEX the highest and AHFS the lowest. The comments of pharmacy faculty and students show that these groups preferred concise, easy-to-use sources; librarians focused on the comprehensiveness, layout, and supporting references of the databases. Conclusion: This study demonstrates the importance of consulting with primary clientele before purchasing databases. Although there are many online drug databases to consider, present findings offer strong support for eFacts, Lexi-Drugs, and DRUGDEX. PMID:14762464

Size distribution of salbutamol/ipratropium aerosols produced by different nebulizers in the absence and presence of heat and humidification.

PubMed

Yang, Ssu-Han; Yang, Tsung-Ming; Lin, Hui-Ling; Tsai, Ying-Huang; Fang, Tien-Pei; Wan, Gwo-Hwa

2018-02-01

Few studies have evaluated the size distribution of inhaled and exhaled aerosolized drugs, or the effect of heated humidification on particle size and lung deposition. The present study evaluated these aspects of bronchodilator (salbutamol/ipratropium) delivery using a lung model in the absence and presence of heat and humidification. We positioned filters to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle size distribution was evaluated using an 8-stage Marple personal cascade impactor with 0.2-μm polycarbonate filters. A greater inhaled drug mass was delivered using a vibrating mesh nebulizer (VMN) than by using a small volume nebulizer (SVN), when heated humidifiers were not employed. When heated and humidified medical gas was used, there was no significant difference between the inhaled drug mass delivered by the VMN and that delivered by the SVN. A significantly greater mass of inhaled 1.55-μm drug particles was produced by the VMN than with the SVN, under heated and humidified conditions. However, the mass median aerodynamic diameters (MMADs) of the aerosolized drug produced by the SVN and VMN did not differ significantly under the same conditions. The VMN produced more fine particles of salbutamol/ipratropium, and the drug particle size clearly increased in the presence of heat and humidification. Copyright © 2017 Elsevier Ltd. All rights reserved.

Test implementation of a school-oriented drug prevention program "Study without Drugs": pre- and post-testing for effectiveness.

PubMed

Ishaak, Fariel; de Vries, Nanne Karel; van der Wolf, Kees

2014-06-11

In this article, the test implementation of a school-oriented drug prevention program "Study without Drugs" is discussed. The aims of this study were to determine the results of the process evaluation and to determine whether the proposed school-oriented drug prevention program during a pilot project was effective for the participating pupils. Sixty second-grade pupils at a junior high school in Paramaribo, Suriname participated in the test implementation. They were divided into two classes. For the process evaluation the students completed a structured questionnaire focusing on content and teaching method after every lesson. Lessons were qualified with a score from 0-10. The process was also evaluated by the teachers through structured interviews. Attention was paid to reach, dose delivered, dose received, fidelity, connection, achieved effects/observed behaviors, areas for improvement, and lesson strengths. The effect evaluation was conducted by using the General Liniair Model (repeated measure). The research (-design) was a pre-experimental design with pre-and post-test. No class or sex differences were detected among the pupils with regard to the assessment of content, methodology, and qualification of the lessons. Post-testing showed that participating pupils obtained an increased knowledge of drugs, their drug-resisting skills were enhanced, and behavior determinants (attitude, subjective norm, self-efficacy, and intention) became more negative towards drugs. From the results of the test implementation can be cautiously concluded that the program "Study without Drugs" may yield positive results when applied in schools). Thus, this pilot program can be considered a step towards the development and implementation of an evidence-based school-oriented program for pupils in Suriname.

Drugs in the Workplace: Research and Evaluation Data. Volume II. Research Monograph 100.

ERIC Educational Resources Information Center

Gust, Steven W., Ed.; And Others

This monograph presents 14 articles on the topics of the nature and extent of drug use by the workforce; drug use and job performance indicators; and drug free workplace program research. These articles are included: (1) Research on Drugs and the Workplace: Introduction and Summary (Steven Gust, Dennis Crouch, J. Michael Walsh); (2) Drug Use…

Pretest Differences in Drug-Related Variables among Intact College Classes: Implications for Outcome Evaluation in Drug Education.

ERIC Educational Resources Information Center

Gonzalez, Gerardo M.; Haney, Michael L.

1992-01-01

Identified significant pretest differences in drug-related variables in college students from alcohol and drug education class (n=99), stress management class (n=44), and social problems class (n=80). Higher levels of alcohol and drug abuse among students in drug abuse course suggests student users are possibly being attracted to course as means…

Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality.

PubMed

de Lima Marson, Fernando Augusto; Bertuzzo, Carmen Silvia; Ribeiro, Jose Dirceu

2015-01-01

Personalized drug therapy for cystic fibrosis (CF) is a long-term dream for CF patients, caregivers, physicians and researchers. After years of study, the fiction of personalized treatment has turned to hope. Basic information about CFTR mutations classes and new treatments is needed if we are to deal properly with the new CF era. The problems involved in this issue, however, should be evaluated with greater care and attention. VX-770 is a new drug available to treat CF patients with some class III CFTR mutations and other drugs are being studied regarding other classes. The scientific literature has constantly given information about each therapy, both in vitro and in vivo. The hope is increasing. Nevertheless the "scientific world" still lacks information about patients' reality and daily health related practical needs. Clinical trials have showed good evaluation of some drugs so far, but clinical response is a wide spectrum yet to be analyzed: CFTR mutations spectrum, costs related to the treatment with new drugs (for VX-770 therapy), variability of CF clinical expression, limitations to test in vitro drugs, absence of good clinical markers to evaluate drug response, absence of long-term studies and with patients below six years old, multidrug treatment used to improve the expression response, and finally, the most important problem, who will benefit from the new drugs therapy, are issues that constitute a barrier that should be overcome. Personalized drug therapy may not be a fiction anymore, but it is not yet a reality for all CF patients.

Estimating Fitness by Competition Assays between Drug Susceptible and Resistant Mycobacterium tuberculosis of Predominant Lineages in Mumbai, India

PubMed Central

Bhatter, Purva; Chatterjee, Anirvan; D'souza, Desiree; Tolani, Monica; Mistry, Nerges

2012-01-01

Background Multi Drug Resistant Tuberculosis (MDR TB) is a threat to global tuberculosis control. A significant fitness cost has been associated with DR strains from specific lineages. Evaluation of the influence of the competing drug susceptible strains on fitness of drug resistant strains may have an important bearing on understanding the spread of MDR TB. The aim of this study was to evaluate the fitness of MDR TB strains, from a TB endemic region of western India: Mumbai, belonging to 3 predominant lineages namely CAS, Beijing and MANU in the presence of drug susceptible strains from the same lineages. Methodology Drug susceptible strains from a single lineage were mixed with drug resistant strain, bearing particular non synonymous mutation (rpoB D516V; inhA, A16G; katG, S315T1/T2) from the same or different lineages. Fitness of M.tuberculosis (M.tb) strains was evaluated using the difference in growth rates obtained by using the CFU assay system. Conclusion/Significance While MANU were most fit amongst the drug susceptible strains of the 3 lineages, only Beijing MDR strains were found to grow in the presence of any of the competing drug susceptible strains. A disproportionate increase in Beijing MDR could be an alarm for an impending epidemic in this locale. In addition to particular non synonymous substitutions, the competing strains in an environment may impact the fitness of circulating drug resistant strains. PMID:22479407

75 FR 386 - Memorandum of Understanding Between the United States Department of Health and Human Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0667... Services, Food and Drug Administration, Center for Drug Evaluation and Research and Northeastern University AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

75 FR 65495 - Draft Guidance for Industry on Qualification Process for Drug Development Tools; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0529...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... framework for interactions between the Center for Drug Evaluation and Research (CDER) and DDT sponsors to...

78 FR 24754 - Guidance for Industry on Regulatory Classification of Pharmaceutical Co-Crystals; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0800... and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... this guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and...

78 FR 37202 - Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

... Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in Food AGENCY: Office... Residues of Veterinary Drugs in Foods (CCRVDF) of the Codex Alimentarius Commission (Codex), which will be... Animal Drug Evaluation, HFV-100, Food and Drug Administration, Center for Veterinary Medicine, 7520...

21 CFR 201.200 - Disclosure of drug efficacy study evaluations in labeling and advertising.

Code of Federal Regulations, 2010 CFR

2010-04-01

... an exhaustive review of labeling claims made for drugs marketed under new-drug and antibiotic drug... classification in lieu of the Academy's classification. (d) For new drugs and antibiotics, supplements to provide... purchaser or prescriber is not misled by being left unaware through the sponsor's silence that a basic...

Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA).

PubMed

do Carmo, Ana Cerúlia Moraes; Piras, Stefânia Schimaneski; Rocha, Nayrton Flávio Moura; Gratieri, Tais

2017-01-01

Objective . The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods . A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results . Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion . Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products.

Corneal critical barrier against the penetration of dexamethasone and lomefloxacin hydrochloride: evaluation by the activation energy for drug partition and diffusion in cornea.

PubMed

Yasueda, Shin-ichi; Higashiyama, Masayo; Yamaguchi, Masazumi; Isowaki, Akiharu; Ohtori, Akira

2007-08-01

The cornea is a solid barrier against drug permeation. We searched the critical barrier of corneal drug permeation using a hydrophobic drug, dexamethasone (DM), and a hydrophilic drug, lomefloxacin hydrochloride (LFLX). The activation energies for permeability of DM and LFLX across the intact cornea were 88.0 and 42.1 kJ/mol, respectively. Their activation energies for permeability across the cornea without epithelium decreased to 33.1 and 16.6 kJ/mol, respectively. The results show that epithelium is the critical barrier on the cornea against the permeation of a hydrophobic drug of DM as well as a hydrophilic drug of LFLX. The activation energy of partition for DM (66.8 kJ/mol) was approximately 3-fold larger than that of diffusion (21.2 kJ/mol). The results indicate that the partition for the hydrophobic drug of DM to the corneal epithelium is the primary barrier. Thermodynamic evaluation of activation energy for the drug permeation parameters is a good approach to investigate the mechanism of drug permeability.

Kidney-on-a-Chip: a New Technology for Predicting Drug Efficacy, Interactions, and Drug-induced Nephrotoxicity.

PubMed

Lee, Jeonghwan; Kim, Sejoong

2018-03-08

The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans. A kidney-on-a-chip is a microfluidic device that allows the culture of living renal cells in 3-dimensional channels and mimics the human microphysiological environment, thus simulating the actual drug filtering, absorption, and secretion process.. In this review, we discuss recent developments in microfluidic culturing technique and describe current and future kidney-on-a-chip applications. We focus on pharmacological interactions and drug-induced nephrotoxicity, and additionally discuss the development of multi-organ chips and their possible applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA)

PubMed Central

do Carmo, Ana Cerúlia Moraes; Piras, Stefânia Schimaneski; Rocha, Nayrton Flávio Moura

2017-01-01

Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products. PMID:28280742

Building a structured monitoring and evaluating system of postmarketing drug use in Shanghai.

PubMed

Du, Wenmin; Levine, Mitchell; Wang, Longxing; Zhang, Yaohua; Yi, Chengdong; Wang, Hongmin; Wang, Xiaoyu; Xie, Hongjuan; Xu, Jianglong; Jin, Huilin; Wang, Tongchun; Huang, Gan; Wu, Ye

2007-01-01

In order to understand a drug's full profile in the post-marketing environment, information is needed regarding utilization patterns, beneficial effects, ADRs and economic value. China, the most populated country in the world, has the largest number of people who are taking medications. To begin to appreciate the impact of these medications, a multifunctional evaluation and surveillance system was developed, the Shanghai Drug Monitoring and Evaluative System (SDMES). Set up by the Shanghai Center for Adverse Drug Reaction Monitoring in 2001, the SDMES contains three databases: a population health data base of middle aged and elderly persons; hospital patient medical records; and a spontaneous ADR reporting database. Each person has a unique identification and Medicare number, which permits record-linkage within and between these three databases. After more than three years in development, the population health database has comprehensive data for more than 320,000 residents. The hospital database has two years of inpatient medical records from five major hospitals, and will be increasing to 10 hospitals in 2007. The spontaneous reporting ADR database has collected 20,205 cases since 2001 from approximately 295 sources, including hospitals, pharmaceutical companies, drug wholesalers and pharmacies. The SDMES has the potential to become an important national and international pharmacoepidemiology resource for drug evaluation.

Drug Utilization on Neonatal Wards: A Systematic Review of Observational Studies

PubMed Central

Rosli, Rosliana; Dali, Ahmad Fauzi; Abd Aziz, Noorizan; Abdullah, Amir Heberd; Ming, Long Chiau; Manan, Mohamed Mansor

2017-01-01

Despite limited evidence on safety and efficacy of drug use in neonates, drugs are extensively used in this age group. However, the availability of information on drug consumption in neonates, especially inpatient neonates, is limited. This paper systematically reviews published studies on drug utilization in hospitalized neonates. A systematic literature review was carried out to identify observational studies published from inception of databases used till August 2016. Four search engines, namely Medline, CINAHL, Embase, and PubMed, were used. Publications written in English that described drug utilization in neonatal wards were selected. Assessment of the data was based on the category of the study design, the objective of study and the method used in reporting drug consumption. A total of 20 drug utilization studies were identified, 12 of which focused on all drug classes, while the other eight evaluated antimicrobials. Studies were reported in Europe (n = 7), the United States (n = 6), India (n = 5), Brazil (n = 1), and Iran (n = 1). Substantial variance with regard to study types (study design and methods), data source, and sample size were found among the selected studies. Of the studies included, 45% were cross-sectional or retrospective, 40% were prospective studies, and the remaining 15% were point prevalence surveys. More than 70% of the studies were descriptive studies, describing drug consumption patterns. Fifteen per cent of the descriptive studies evaluated changes in drug utilization patterns in neonates. Volume of units was the most prevalent method used for reporting all drug categories. The ATC/DDD system for reporting drug use was only seen in studies evaluating antimicrobials. The most commonly reported drugs across all studies are anti-infectives for systemic use, followed by drugs for the cardiovascular system, the nervous system and the respiratory system. Ampicillin and gentamicin were the most prescribed antimicrobials in hospitalized neonates. The present review reveals that neonates are exposed to a high number of drugs and various methods are used to report drug consumption in this age group. The best measure of drug consumption to quantify prevalence of drug use in neonates remains to be identified and additional research in this area is warranted. PMID:28228724

Points to consider: efficacy and safety evaluations in the clinical development of ultra-orphan drugs.

PubMed

Maeda, Kojiro; Kaneko, Masayuki; Narukawa, Mamoru; Arato, Teruyo

2017-08-23

The unmet medical needs of individuals with very rare diseases are high. The clinical trial designs and evaluation methods used for 'regular' drugs are not applicable in the clinical development of ultra-orphan drugs (<1000 patients) in many cases. In order to improve the clinical development of ultra-orphan drugs, we examined several points regarding the efficient evaluations of drug efficacy and safety that could be conducted even with very small sample sizes, based on the review reports of orphan drugs approved in Japan. The clinical data packages of 43 ultra-orphan drugs approved in Japan from January 2001 to December 2014 were investigated. Japanese clinical trial data were not included in the clinical data package for eight ultra-orphan drugs, and non-Japanese clinical trial data were included for six of these eight drug. Japanese supportive data that included retrospective studies, published literature, clinical research and Japanese survey results were clinical data package attachments in 22 of the 43 ultra-orphan drugs. Multinational trials were conducted for three ultra-orphan drugs. More than two randomized controlled trials (RCTs) were conducted for only 11 of the 43 ultra-orphan drugs. The smaller the number of patients, the greater the proportion of forced titration and optional titration trials were conducted. Extension trials were carried out for enzyme preparations and monoclonal antibodies with high ratio. Post-marketing surveillance of all patients was required in 36 of the 43 ultra-orphan drugs. For ultra-orphan drugs, clinical endpoints were used as the primary efficacy endpoint of the pivotal trial only for two drugs. The control groups in RCTs were classified as follows: placebo groups different dosage groups, and active controls groups. Sample sizes have been determined on the basis of feasibility for some ultra-orphan drugs. We provide "Draft Guidance on the Clinical Development of Ultra-Orphan Drugs" based on this research. The development of ultra-orphan drugs requires various arrangements regarding evidence collection, data sources and the clinical trial design. We expect that this draft guidance is useful for ultra-orphan drugs developments in future.

Analysis of questions about use of drugs in breastfeeding to Norwegian drug information centres.

PubMed

Jahnsen, Jan Anker; Widnes, Sofia Frost; Schjøtt, Jan

2018-01-01

Health professionals may advise women to either stop breastfeeding or drug treatment due to restrictive advice in drug monographs. Regional medicines information and pharmacovigilance centres in Norway (RELIS) provide free and industry-independent answers to questions about drugs and breastfeeding documented in a full-text, searchable database (RELIS database). We used the RELIS database to describe which health care practitioners sought information about medication safety in lactation, most common drugs involved, advice provided and which resources were used to provide the advice. A random selection of 100 question-answer pairs (QAPs) from the RELIS database indexed with "BREASTFEEDING" in the period from January 2011 to December 2015 was analysed. Inclusion criteria were queries from health professionals about drugs. Questions about herbal supplements and other exposures not classified as drugs were excluded. The QAPs were manually analysed for compatibility of one or several drugs with breastfeeding, health care profession and workplace of enquirer in addition to advice and search strategy used. In the 100 QAPs there were enquires about 152 drugs. Seventy-four questions concerned a single drug, but the number of drugs evaluated varied between 1 and 16. Fifty-nine questions were from physicians, 34 from nurses or midwives, two from pharmacists and two from other health professionals. Questions from physicians contained 93 drug evaluations (61%), nurses or midwives 47 (31%) and pharmacists seven (5%). The most frequent categories of drugs were antidepressants, antiepileptics and immunosuppressants. The most asked about drugs were lamotrigine, codeine, quetiapine and escitalopram. Fifty-nine percent of the drugs were deemed safe while breastfeeding, 16% if precautions were taken and 12% not recommended. Thirty-nine percent of the drug evaluations used an advanced literature search strategy, and this was significantly ( p  < 0.05) more likely when the enquirer was a physician. This analysis of questions to Norwegian medicines information centres about medicine use in breastfeeding indicates the need for communication about safety of drugs affecting the nervous system, primarily to medical doctors and midwives. In the majority of cases the medicine information centre can reassure about the safety of breastfeeding while taking a drug.

Questionnaire design and the recall of pharmacological treatments: a systematic review.

PubMed

Gama, Helena; Correia, Sofia; Lunet, Nuno

2009-03-01

We aimed to review systematically the published evidence regarding the effect of questionnaire design on the recall of pharmacological treatments. The electronic databases Pubmed, EMBASE, and Cochrane Library were searched from inception to October 2007, using the following search terms: drug utilization, pharmaceutical preparations, pharmacoepidemiology, validation studies, methods, epidemiologic methods, interviews, data collection, and questionnaires. Drug utilization studies comparing different types of questionnaire or methods of questionnaire administration were included. Backward and forward citation tracking were also conducted. Eight studies were included in the systematic review, comparing questions asking for specific drugs or indications with open-ended questions (n = 5), evaluating the use of memory aids (n = 1), or studying the influence of response order on recall (n = 2). The studies were heterogeneous, namely regarding the populations evaluated (e.g., pregnant women, hypertensive patients, general population), mode of questionnaire administration (e.g., personal or telephone interview, self-administered), recall period (e.g., current use, 1 week, previous episode of a disease), or drugs evaluated (e.g., analgesics, antimalarials, all medicines). Despite the lack of standardization in presentation of results, the prevalence of drug use may vary between 5 and 40% when drug names and indications or pictures are used as memory aids, or as a result of primacy effects in self-administered questionnaires. The yielding of the questionnaires depended on the pharmacological groups evaluated. Scientific work regarding methods for drug utilization data collection is scarce. The available evidence highlights the importance of knowing the questionnaire characteristics for a proper interpretation of results from drug utilization studies. (c) 2009 John Wiley & Sons, Ltd.

Data available on the impact of drug use on transportation safety

DOT National Transportation Integrated Search

1988-05-01

The report assesses the available data on drug use in transportation, the relevant experimental research on the impacts of drugs, and the state-of-the-art in drug analysis and toxicological quality control. The report describes and evaluates: informa...

Field test of on-site drug detection devices

DOT National Transportation Integrated Search

2000-10-01

This NHTSA-sponsored study reports the findings of a field evaluation of five on-site drug screening devices used by law enforcement to screen for illicit drugs among drivers suspected of driving under the influence (DUI) of alcohol or other drugs. I...

77 FR 60440 - Clinical Investigator Training Course

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Clinical Investigator Training Course AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration's (FDA) Center for Drug Evaluation and Research/Office of Medical...

21 CFR 70.42 - Criteria for evaluating the safety of color additives.

Code of Federal Regulations, 2011 CFR

2011-04-01

... additives. 70.42 Section 70.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVES Safety Evaluation § 70.42 Criteria for evaluating the safety of color additives. (a) In deciding whether a petition is complete and suitable for filing and in reaching a decision...

Handbook for Evaluating Drug and Alcohol Prevention Programs: Staff/Team Evaluation of Prevention Programs (STEPP).

ERIC Educational Resources Information Center

Hawkins, J. David; Nederhood, Britt

This handbook was developed for the purpose of providing drug and alcohol prevention program managers with a comprehensive yet easy-to-use tool to help their evaluation efforts. The handbook emphasizes program staff members working together as a team. It provides instruments and activities for determining program effectiveness, as well as…

The social construction of "evidence-based'' drug prevention programs: a reanalysis of data from the Drug Abuse Resistance Education (DARE) program.

PubMed

Gorman, Dennis M; Huber, J Charles

2009-08-01

This study explores the possibility that any drug prevention program might be considered ;;evidence-based'' given the use of data analysis procedures that optimize the chance of producing statistically significant results by reanalyzing data from a Drug Abuse Resistance Education (DARE) program evaluation. The analysis produced a number of statistically significant differences between the DARE and control conditions on alcohol and marijuana use measures. Many of these differences occurred at cutoff points on the assessment scales for which post hoc meaningful labels were created. Our results are compared to those from evaluations of programs that appear on evidence-based drug prevention lists.

How Often Are Drugs Made Available Under the Food and Drug Administration's Expanded Access Process Approved?

PubMed

McKee, Amy E; Markon, André O; Chan-Tack, Kirk M; Lurie, Peter

2017-10-01

In this review of individual patient expanded-access requests to the Center for Drug Evaluation and Research for the period Fiscal Year 2010 to Fiscal Year 2014, we evaluated the number of applications received and the number allowed to proceed. We also evaluated whether drugs and certain biologics obtained under expanded access went on to be approved by the Food and Drug Administration. Finally, we considered concerns that adverse events occurring during expanded access might place sponsors at risk for legal liability. Overall, 98% of individual patient expanded-access requests were allowed to proceed. During the study period, among drugs without a previous approval for any indication or dosage form, 24% of unique drugs (ie, multiple applications for access to the same drug were considered to relate to 1 unique drug), and 20% of expanded-access applications received marketing approval by 1 year after initial submission; 43% and 33%, respectively, were approved by 5 years after initial submission. A search of 3 legal databases and a database of news articles did not appear to identify any product liability cases arising from the use of a product in expanded access. Our analyses seek to give physicians and patients a realistic perspective on the likelihood of a drug's approval as well as certain information regarding the product liability risks for commercial sponsors when providing expanded access to investigational drugs. The US Food and Drug Administration (FDA)'s expanded-access program maintains a careful balance between authorizing patient access to potentially beneficial drugs and protecting them from drugs that may have unknown risks. At the same time, the agency wishes to maintain the integrity of the clinical trials process, ultimately the best way to get safe and effective drugs to patients. © 2017, The American College of Clinical Pharmacology.

In Vitro-In Vivo Extrapolation of Metabolism- and Transporter-Mediated Drug-Drug Interactions-Overview of Basic Prediction Methods.

PubMed

Yoshida, Kenta; Zhao, Ping; Zhang, Lei; Abernethy, Darrell R; Rekić, Dinko; Reynolds, Kellie S; Galetin, Aleksandra; Huang, Shiew-Mei

2017-09-01

Evaluation of drug-drug interaction (DDI) risk is vital to establish benefit-risk profiles of investigational new drugs during drug development. In vitro experiments are routinely conducted as an important first step to assess metabolism- and transporter-mediated DDI potential of investigational new drugs. Results from these experiments are interpreted, often with the aid of in vitro-in vivo extrapolation methods, to determine whether and how DDI should be evaluated clinically to provide the basis for proper DDI management strategies, including dosing recommendations, alternative therapies, or contraindications under various DDI scenarios and in different patient population. This article provides an overview of currently available in vitro experimental systems and basic in vitro-in vivo extrapolation methodologies for metabolism- and transporter-mediated DDIs. Published by Elsevier Inc.

Evaluation of the potential use of hybrid LC-MS/MS for active drug quantification applying the 'free analyte QC concept'.

PubMed

Jordan, Gregor; Onami, Ichio; Heinrich, Julia; Staack, Roland F

2017-11-01

Assessment of active drug exposure of biologics may be crucial for drug development. Typically, ligand-binding assay methods are used to provide free/active drug concentrations. To what extent hybrid LC-MS/MS procedures enable correct 'active' drug quantification is currently under consideration. Experimental & results: The relevance of appropriate extraction condition was evaluated by a hybrid target capture immuno-affinity LC-MS/MS method using total and free/active quality controls (QCs). The rapid extraction (10 min) provided correct results, whereas overnight incubation resulted in significant overestimation of the free/active drug (monclonal antibody) concentration. Conventional total QCs were inappropriate to determine optimal method conditions in contrast to free/active QCs. The 'free/active analyte QC concept' enables development of appropriate extraction conditions for correct active drug quantification by hybrid LC-MS/MS.

Target specific delivery of anticancer drug in silk fibroin based 3D distribution model of bone-breast cancer cells.

PubMed

Subia, Bano; Dey, Tuli; Sharma, Shaily; Kundu, Subhas C

2015-02-04

To avoid the indiscriminating action of anticancer drugs, the cancer cell specific targeting of drug molecule becomes a preferred choice for the treatment. The successful screening of the drug molecules in 2D culture system requires further validation. The failure of target specific drug in animal model raises the issue of creating a platform in between the in vitro (2D) and in vivo animal testing. The metastatic breast cancer cells migrate and settle at different sites such as bone tissue. This work evaluates the in vitro 3D model of the breast cancer and bone cells to understand the cellular interactions in the presence of a targeted anticancer drug delivery system. The silk fibroin based cytocompatible 3D scaffold is used as in vitro 3D distribution model. Human breast adenocarcinoma and osteoblast like cells are cocultured to evaluate the efficiency of doxorubicin loaded folic acid conjugated silk fibroin nanoparticle as drug delivery system. Decreasing population of the cancer cells, which lower the levels of vascular endothelial growth factors, glucose consumption, and lactate production are observed in the drug treated coculture constructs. The drug treated constructs do not show any major impact on bone mineralization. The diminished expression of osteogenic markers such as osteocalcein and alkaline phosphatase are recorded. The result indicates that this type of silk based 3D in vitro coculture model may be utilized as a bridge between the traditional 2D and animal model system to evaluate the new drug molecule (s) or to reassay the known drug molecules or to develop target specific drug in cancer research.

Roadside drug testing: An evaluation of the Alere DDS® 2 mobile test system.

PubMed

Rohrig, Timothy P; Moore, Christine M; Stephens, Kimberly; Cooper, Kelsey; Coulter, Cynthia; Baird, Tyson; Garnier, Margaux; Miller, Samuel; Tuyay, James; Osawa, Kei; Chou, Joshua; Nuss, Carson; Collier, Jeff; Wittman, Karen Cudlin

2018-04-01

The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however, there are insufficient numbers of these highly trained drug recognition experts (DREs) available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages, particularly as they pertain to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory-based analysis, and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing, both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of the driver should still be considered the most important aspect for arrest and further action. Copyright © 2017 John Wiley & Sons, Ltd.

Evaluation of the artificial membrane permeability of drugs by digital simulation.

PubMed

Nakamura, Mayumi; Osakai, Toshiyuki

2016-08-25

A digital simulation method has been developed for evaluating the membrane permeability of drugs in the parallel artificial membrane permeation assay (PAMPA). The simulation results have shown that the permeability coefficient (log Ppampa) of drugs is linearly increased with increasing their distribution coefficient (log KD,M) to the lipid membrane, i.e., the hydrophobicity of the drug molecules. However, log Ppampa shows signs of leveling off for highly hydrophobic drugs. Such a dependence of log Ppampa is in harmony with the reported experimental data, and has been well explained in terms of the change in the rate-determining step from the diffusion in the membrane to that in the unstirred water layer (UWL) on both sides of the membrane. Additionally, the effects of several factors, including lag time, diffusion coefficient, pH, and pKa, on the permeability coefficient have been well simulated. It has thus been suggested that the proposed method should be promising for in silico evaluation of the membrane permeability of drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

[Discussion on efficacy evaluation thought and method for innovation medicine of Chinese herbal compound formula based on clinical application characteristics].

PubMed

Sun, Jian-Ning; Sun, Wen-Yan; Dong, Shi-Fen

2017-03-01

The Chinese herbal compound formula preparation was made based on theory of Chinese medicine, which was confirmed by long period clinical application, and with multi-compound and multi-target characteristics. During the exploitation process of innovation medicine of Chinese herbal compound formula, selecting and speeding up the research development of drugs with clinical value shall be paid more attention, and as request of rules involved in new drug research and development, the whole process management should be carried out, including project evaluation, manufacturing process determination, establishment of quality control standards, evaluation for pharmacological and toxic effect, as well as new drug application process. This reviews was aimed to give some proposals for pharmacodynamics research methods involved in exploration of Chinese herbal compound formula preparation, including： ①the endpoint criteria should meet the clinical attribution of new drugs; ②the pre-clinical pharmacodynamics evaluation should be carried on appropriate animal models according to the characteristics of diagnosis and therapy of Chinese medicine and observation indexes; ③during the innovation of drug for infants and children, information on drug action conforming to physiological characteristics of infants and children should be supplied, and the pharmacodynamics and toxicology research shall be conducted in immature rats according to the body weight of children. In a summary, the clinical application characteristics are the important criteria for evaluation of pharmacological effect of innovation medicine of Chinese herbal compound formula. Copyright© by the Chinese Pharmaceutical Association.

Company observational post-marketing studies: drug risk assessment and drug research in special populations--a study-based analysis.

PubMed

Hasford, J; Lamprecht, T

1998-01-01

Company observational post-marketing studies (COPS) claim to provide essential data about drug risks and effectiveness in special populations not admitted to pre-approval clinical trials. Since COPS are often mainly regarded as a marketing activity, this study-based analysis tries to evaluate the scientific contributions of COPS. Thirty-five COPS were identified by hand-searching through medical journals, writing to pharmaceutical manufacturers and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated NSAIDs and 12 evaluated various other indications. Thirty-five COPS listed effectiveness, 31 listed safety and 8 listed patient compliance as principal objectives. Not a single COPS included a control group. Seventeen of 21 evaluable COPS mentioned extensive exclusion criteria similar to those in clinical trials. Median observation time was 8 weeks, too short for chronic diseases and for adverse drug reactions with longer latency periods. One new adverse event was regarded. Global assessments of the outcomes by physicians dominated and were not based on objective clinical findings. None of the studies specified any details concerning the standardisation of observations or quality-control procedures. The current COPS scheme does not contribute significantly to our knowledge of drug safety and the effects in special populations. Despite serious criticism over the past 20 years, the poor quality of COPS compared with dramatic improvements of pre-approval trials - implies a need for detailed guidelines for non-experimental phase IV research, similar to the Good Clinical Practice-Guideline of the European Community.

Economic evaluation of drug abuse treatment and HIV prevention programs in pregnant women: a systematic review.

PubMed

Ruger, Jennifer Prah; Lazar, Christina M

2012-01-01

Drug abuse and transmission of HIV during pregnancy are public health problems that adversely affect pregnant women, their children and surrounding communities. Programs that address this vulnerable population have the ability to be cost-effective due to resulting cost savings for mother, child and society. Economic evaluations of programs that address these issues are an important tool to better understand the costs of services and create sustainable healthcare systems. This study critically examined economic evaluations of drug abuse treatment and HIV prevention programs in pregnant women. A systematic review was conducted using the criteria recommended by the Panel on Cost-Effectiveness in Health and Medicine and the British Medical Journal (BMJ) checklist for economic evaluations. The search identified 6 economic studies assessing drug abuse treatment for pregnant women, and 12 economic studies assessing programs that focus on prevention of mother-to-child transmission (PMTCT) of HIV. Results show that many programs for drug abuse treatment and PMTCT among pregnant women are cost-effective or even cost-saving. This study identified several shortcomings in methodology and lack of standardization of current economic evaluations. Efforts to address methodological challenges will help make future studies more comparable and have more influence on policy makers, clinicians and the public. Copyright © 2011 Elsevier Ltd. All rights reserved.

Antibiotic toxicity and absorption in zebrafish using liquid chromatography-tandem mass spectrometry.

PubMed

Zhang, Fan; Qin, Wei; Zhang, Jing-Pu; Hu, Chang-Qin

2015-01-01

Evaluation of drug toxicity is necessary for drug safety, but in vivo drug absorption is varied; therefore, a rapid, sensitive and reliable method for measuring drugs is needed. Zebrafish are acceptable drug toxicity screening models; we used these animals with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in a multiple reaction monitoring mode to quantify drug uptake in zebrafish to better estimate drug toxicity. Analytes were recovered from zebrafish homogenate by collecting supernatant. Measurements were confirmed for drugs in the range of 10-1,000 ng/mL. Four antibiotics with different polarities were tested to explore any correlation of drug polarity, absorption, and toxicity. Zebrafish at 3 days post-fertilization (dpf) absorbed more drug than those at 6 h post-fertilization (hpf), and different developmental periods appeared to be differentially sensitive to the same compound. By observing abnormal embryos and LD50 values, zebrafish embryos at 6 hpf were considered to be suitable for evaluating embryotoxicity. Also, larvae at 3 dpf were adapted to measure acute drug toxicity in adult mammals. Thus, we can exploit zebrafish to study drug toxicity and can reliably quantify drug uptake with LC-MS/MS. This approach will be helpful for future studies of toxicology in zebrafish.

Adsorption of drugs onto a pH responsive poly(N,N-dimethyl aminoethyl methacrylate) grafted anion-exchange membrane in vitro.

PubMed

Karppi, Jouni; Akerman, Satu; Akerman, Kari; Sundell, Annika; Nyyssönen, Kristiina; Penttilä, Ilkka

2007-06-29

The influence of charge and lipophilicity of acidic and basic model drugs on their adsorption onto poly(N,N-dimethyl aminoethyl methacrylic acid) grafted poly(vinylidene fluoride) (DMAEMA-PVDF) membranes was evaluated. The effect of serum proteins (albumin, IgG) and hormones (cortisol, free thyroxine (T(4)F) and thyrotropin (TSH)) on drug adsorption was also studied. Acidic model drugs (antiepileptics and benzodiazepies) adsorbed to a greater extent onto the membrane from Hepes buffer at ionic strength of 25mM and pH 7.0 than basic drugs (antidepressants) did. Adsorption of acidic model drugs was based on electrostatic interactions between positively charged tertiary amino groups of DMAEMA side-chain and acidic negatively charged drug. Albumin diminished the adsorption of drugs from serum onto the membrane. Lipophilicity was related to the adsorption of acidic model drugs from serum onto the membrane. The degree of grafting had the greatest effect on adsorption of lipophilic drugs, but no influence was observed on adsorption of hydrophilic drugs. The present results showed that acidic drugs and albumin adsorbed onto the membrane, which suggests that the PVDF-DMAEMA membrane may be suitable for separating acidic drugs from protein-free substances for subsequent monitoring and evaluation.

77 FR 49446 - Gastrointestinal Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-16

... Person: Cindy Hong, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New... development programs necessary to support approval of parenteral lipid emulsion products as nutritional...

76 FR 3913 - National Institute on Drug Abuse; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-21

... evaluation of individual intramural programs and projects conducted by the National Institute on Drug Abuse... individual investigators. Place: Intramural Research Program, National Institute on Drug Abuse, NIH, Johns... Psychologist, Clinical Pharmacology Branch, Intramural Research Program, National Institute on Drug Abuse...

21 CFR 640.104 - Potency.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the Center for Biologics Evaluation and Research, Food and Drug Administration, as indicated in... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Potency. 640.104 Section 640.104 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL...

21 CFR 640.104 - Potency.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the Center for Biologics Evaluation and Research, Food and Drug Administration, as indicated in... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Potency. 640.104 Section 640.104 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL...

Pancreatic adenocarcinoma response to chemotherapy enhanced with non-invasive radio frequency evaluated via an integrated experimental/computational approach.

PubMed

Ware, Matthew J; Curtis, Louis T; Wu, Min; Ho, Jason C; Corr, Stuart J; Curley, Steven A; Godin, Biana; Frieboes, Hermann B

2017-06-13

Although chemotherapy combined with radiofrequency exposure has shown promise in cancer treatment by coupling drug cytotoxicity with thermal ablation or thermally-induced cytotoxicity, limited access of the drug to tumor loci in hypo-vascularized lesions has hampered clinical application. We recently showed that high-intensity short-wave capacitively coupled radiofrequency (RF) electric-fields may reach inaccessible targets in vivo. This non-invasive RF combined with gemcitabine (Gem) chemotherapy enhanced drug uptake and effect in pancreatic adenocarcinoma (PDAC), notorious for having poor response and limited therapeutic options, but without inducing thermal injury. We hypothesize that the enhanced cytotoxicity derives from RF-facilitated drug transport in the tumor microenvironment. We propose an integrated experimental/computational approach to evaluate chemotherapeutic response combined with RF-induced phenotypic changes in tissue with impaired transport. Results show that RF facilitates diffusive transport in 3D cell cultures representing hypo-vascularized lesions, enhancing drug uptake and effect. Computational modeling evaluates drug vascular extravasation and diffusive transport as key RF-modulated parameters, with transport being dominant. Assessment of hypothetical schedules following current clinical protocol for Stage-IV PDAC suggests that unresponsive lesions may be growth-restrained when exposed to Gem plus RF. Comparison of these projections to experiments in vivo indicates that synergy may result from RF-induced cell phenotypic changes enhancing drug transport and cytotoxicity, thus providing a potential baseline for clinically-focused evaluation.

The anticholinergic impregnation scale: Towards the elaboration of a scale adapted to prescriptions in French psychiatric settings.

PubMed

Briet, Jeanne; Javelot, Hervé; Heitzmann, Edwige; Weiner, Luisa; Lameira, Catherine; D'Athis, Philippe; Corneloup, Marie; Vailleau, Jean-Louis

2017-09-01

Some drugs have anticholinergic activity and can cause peripheral or central side effects. Several scales exist to evaluate the potential anticholinergic effect of prescribed drugs but: (i) they are validated in the elderly and mainly assess the cognitive side effect of treatments; (ii) they do not concern some of the drugs frequently used in clinical psychiatry in France. The aim of our study is to develop a new scale, the anticholinergic impregnation scale (AIS), with drugs used in France and based on an assessment of the drugs used against peripheral anticholinergic adverse effects. We assigned a score, ranging from 1 to 3, to a list of 128 drugs with a consensus approach obtained via literature data and expert opinions. We collected data from 7278 prescriptions in 34 French psychiatric facilities: age, sex, atropinic drugs, laxatives and treatments of xerophthalmia and xerostomia, in order to evaluate the association between AIS score and the prescription of drugs aiming to reduce peripheral anticholinergic side effects. The most frequently prescribed drugs were cyamemazine (n=1429; 20%) and tropatepine (n=1403; 19%), two drugs marketed almost exclusively in France and with a score of 3. The frequency of patients with a high AIS score, greater than 5, was significantly higher in patients who received laxatives and treatments of xerostomia. AIS score represents the first validated solution to evaluate anticholinergic load in psychiatry settings in France. The anticholinergic problem remains underevaluated in mental health settings. In order to rule out the confounding factor of mental disease, assessment of peripheral side effects can be considered more objective than the evaluation of cognitive function in psychiatric patients. Building scales appropriate for each state also appear essential to obtain an useful and effective tool in clinical practice. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Quality of Reporting of Bioequivalence Trials Comparing Generic to Brand Name Drugs: A Methodological Systematic Review

PubMed Central

van der Meersch, Amélie; Dechartres, Agnès; Ravaud, Philippe

2011-01-01

Background Generic drugs are used by millions of patients for economic reasons, so their evaluation must be highly transparent. Objective To assess the quality of reporting of bioequivalence trials comparing generic to brand-name drugs. Methodology/Principal Findings PubMed was searched for reports of bioequivalence trials comparing generic to brand-name drugs between January 2005 and December 2008. Articles were included if the aim of the study was to assess the bioequivalency of generic and brand-name drugs. We excluded case studies, pharmaco-economic evaluations, and validation dosage assays of drugs. We evaluated whether important information about funding, methodology, location of trials, and participants were reported. We also assessed whether the criteria required by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) to conclude bioequivalence were reported and that the conclusions were in agreement with the results. We identified 134 potentially relevant articles but eliminated 55 because the brand-name or generic drug status of the reference drug was unknown. Thus, we evaluated 79 articles. The funding source and location of the trial were reported in 41% and 56% of articles, respectively. The type of statistical analysis was reported in 94% of articles, but the methods to generate the randomization sequence and to conceal allocation were reported in only 15% and 5%, respectively. In total, 65 articles of single-dose trials (89%) concluded bioequivalence. Of these, 20 (31%) did not report the 3 criteria within the limits required by the FDA and 11 (17%) did not report the 2 criteria within the limits required by the EMA. Conclusions/Significance Important information to judge the validity and relevance of results are frequently missing in published reports of trials assessing generic drugs. The quality of reporting of such trials is in need of improvement. PMID:21858184

Development and Evaluation of Cefadroxil Drug Loaded Biopolymeric Films Based on Chitosan-Furfural Schiff Base

PubMed Central

Dixit, Ritu B.; Uplana, Rahul A.; Patel, Vishnu A.; Dixit, Bharat C.; Patel, Tarosh S.

2010-01-01

Cefadroxil drug loaded biopolymeric films of chitosan-furfural schiff base were prepared by reacting chitosan with furfural in presence of acetic acid and perchloric acid respectively for the external use. Prepared films were evaluated for their strength, swelling index, thickness, drug content, uniformity, tensile strength, percent elongation, FTIR spectral analysis and SEM. The results of in vitro diffusion studies revealed that the films exhibited enhanced drug diffusion as compared to the films prepared using untreated chitosan. The films also demonstrated good to moderate antibacterial activities against selective gram positive and gram negative bacteria. PMID:21179325

Correlation of dissolution and disintegration results for an immediate-release tablet.

PubMed

Nickerson, Beverly; Kong, Angela; Gerst, Paul; Kao, Shangming

2018-02-20

The drug release rate of a rapidly dissolving immediate-release tablet formulation with a highly soluble drug is proposed to be controlled by the disintegration rate of the tablet. Disintegration and dissolution test methods used to evaluate the tablets were shown to discriminate manufacturing process differences and compositionally variant tablets. In addition, a correlation was established between disintegration and dissolution. In accordance with ICH Q6A, this work demonstrates that disintegration in lieu of dissolution is suitable as the drug product quality control method for evaluating this drug product. Copyright © 2017 Elsevier B.V. All rights reserved.

"SPECDA"-A Comprehensive Approach to the Delivery of Substance Abuse Prevention Services in the New York City School Systems.

ERIC Educational Resources Information Center

Blotner, Roberta; Lilly, Levander

1986-01-01

Evaluates SPECDA (School Program to Educate and Control Drug Abuse) a comprehensive substance abuse prevention program which links drug counselors and police officers in teams to provide drug education. Results indicated significant positive changes in children's knowledge about drugs, attitudes toward drugs, and attitudes toward polic officers…

Curricula, Competition and Conventional Bonds: The Educational Role in Drug Control.

ERIC Educational Resources Information Center

Norland, Stephen; And Others

1996-01-01

Evaluations of school curricular drug control efforts show they are only modestly successful because they are based on an inaccurate theory of drug taking. Social control theory is suggested as a better model of drug taking and drug resistance. Asserts strong bonds to school decrease the likelihood of interaction with delinquent peers and thereby…

Multiple Measures of Juvenile Drug Court Effectiveness: Results of a Quasi-Experimental Design

ERIC Educational Resources Information Center

Rodriguez, Nancy; Webb, Vincent J.

2004-01-01

Prior studies of juvenile drug courts have been constrained by small samples, inadequate comparison groups, or limited outcome measures. The authors report on a 3-year evaluation that examines the impact of juvenile drug court participation on recidivism and drug use. A quasi-experimental design is used to compare juveniles assigned to drug court…

The effectiveness and cost-effectiveness of diversion and aftercare programmes for offenders using class A drugs: a systematic review and economic evaluation.

PubMed

Hayhurst, Karen P; Leitner, Maria; Davies, Linda; Flentje, Rachel; Millar, Tim; Jones, Andrew; King, Carlene; Donmall, Michael; Farrell, Michael; Fazel, Seena; Harris, Rochelle; Hickman, Matthew; Lennox, Charlotte; Mayet, Soraya; Senior, Jane; Shaw, Jennifer

2015-01-01

The societal costs of problematic class A drug use in England and Wales exceed £15B; drug-related crime accounts for almost 90% of costs. Diversion plus treatment and/or aftercare programmes may reduce drug-related crime and costs. To assess the effectiveness and cost-effectiveness of diversion and aftercare for class A drug-using offenders, compared with no diversion. Adult class A drug-using offenders diverted to treatment or an aftercare programme for their drug use. Programmes to identify and divert problematic drug users to treatment (voluntary, court mandated or monitored services) at any point within the criminal justice system (CJS). Aftercare follows diversion and treatment, excluding care following prison or non-diversionary drug treatment. Thirty-three electronic databases and government online resources were searched for studies published between January 1985 and January 2012, including MEDLINE, PsycINFO and ISI Web of Science. Bibliographies of identified studies were screened. The UK Drug Data Warehouse, the UK Drug Treatment Outcomes Research Study and published statistics and reports provided data for the economic evaluation. Included studies evaluated diversion in adult class A drug-using offenders, in contact with the CJS. The main outcomes were drug use and offending behaviour, and these were pooled using meta-analysis. The economic review included full economic evaluations for adult opiate and/or crack, or powder, cocaine users. An economic decision analytic model, estimated incremental costs per unit of outcome gained by diversion and aftercare, over a 12-month time horizon. The perspectives included the CJS, NHS, social care providers and offenders. Probabilistic sensitivity analysis and one-way sensitivity analysis explored variance in parameter estimates, longer time horizons and structural uncertainty. Sixteen studies met the effectiveness review inclusion criteria, characterised by poor methodological quality, with modest sample sizes, high attrition rates, retrospective data collection, limited follow-up, no random allocation and publication bias. Most study samples comprised US methamphetamine users. Limited meta-analysis was possible, indicating a potential small impact of diversion interventions on reducing drug use [odds ratio (OR) 1.68, 95% confidence interval (CI) 1.12 to 2.53 for reduced primary drug use, and OR 2.60, 95% CI 1.70 to 3.98 for reduced use of other drugs]. The cost-effectiveness review did not identify any relevant studies. The economic evaluation indicated high uncertainty because of variance in data estimates and limitations in the model design. The primary analysis was unclear whether or not diversion was cost-effective. The sensitivity analyses indicated some scenarios where diversion may be cost-effective. Nearly all participants (99.6%) in the effectiveness review were American (Californian) methamphetamine users, limiting transfer of conclusions to the UK. Data and methodological limitations mean it is unclear whether or not diversion is effective or cost-effective. High-quality evidence for the effectiveness and cost-effectiveness of diversion schemes is sparse and does not relate to the UK. Importantly this research identified a range of methodological limitations in existing evidence. These highlight the need for research to conceptualise, define and develop models of diversion programmes and identify a core outcome set. A programme of feasibility, pilot and definitive trials, combined with process evaluation and qualitative research is recommended to assess the effectiveness and cost-effectiveness of diversionary interventions in class A drug-using offenders. The National Institute for Health Research Health Technology Assessment programme.

Evaluation of automated enzyme immunoassays for five anticonvulsants and theophylline adapted to a centrifugal analyzer.

PubMed

Urquhart, N; Godolphin, W; Campbell, D J

1979-05-01

We report a clinical evaluation of the enzyme immunoassay (EMIT) performed with the GEMSAEC centrifugal analyzer as compared to gas-liquid and liquid chromatography for anticonvulsant drugs and theophylline, respectively. A good correlation was obtained for all drugs, although some difficulties were experienced with one lot of reagent for ethosuximide. The analyzer has an economic advantage if many samples are being analyzed for few drugs in each sample.

Evaluation of the United States Drug War Policy Abroad: A Case Study in Colombia

DTIC Science & Technology

2010-12-01

Case Study in Colombia By: Kevin T. Wright and Joseph S. Hamilton December 2010 Advisors: David R. Henderson, John Enns...States Drug War Policy Abroad: A Case Study in Colombia 6. AUTHOR(S) Kevin T. Wright, Joseph S. Hamilton 5. FUNDING NUMBERS 7. PERFORMING...public release; distribution is unlimited EVALUATION OF THE UNITED STATES DRUG WAR POLICY ABROAD: A CASE STUDY IN COLOMBIA Kevin T. Wright

Clinical decision support tools: performance of personal digital assistant versus online drug information databases.

PubMed

Clauson, Kevin A; Polen, Hyla H; Marsh, Wallace A

2007-12-01

To evaluate personal digital assistant (PDA) drug information databases used to support clinical decision-making, and to compare the performance of PDA databases with their online versions. Prospective evaluation with descriptive analysis. Five drug information databases available for PDAs and online were evaluated according to their scope (inclusion of correct answers), completeness (on a 3-point scale), and ease of use; 158 question-answer pairs across 15 weighted categories of drug information essential to health care professionals were used to evaluate these databases. An overall composite score integrating these three measures was then calculated. Scores for the PDA databases and for each PDA-online pair were compared. Among the PDA databases, composite rankings, from highest to lowest, were as follows: Lexi-Drugs, Clinical Pharmacology OnHand, Epocrates Rx Pro, mobileMicromedex (now called Thomson Clinical Xpert), and Epocrates Rx free version. When we compared database pairs, online databases that had greater scope than their PDA counterparts were Clinical Pharmacology (137 vs 100 answers, p<0.001), Micromedex (132 vs 96 answers, p<0.001), Lexi-Comp Online (131 vs 119 answers, p<0.001), and Epocrates Online Premium (103 vs 98 answers, p=0.001). Only Micromedex online was more complete than its PDA version (p=0.008). Regarding ease of use, the Lexi-Drugs PDA database was superior to Lexi-Comp Online (p<0.001); however, Epocrates Online Premium, Epocrates Online Free, and Micromedex online were easier to use than their PDA counterparts (p<0.001). In terms of composite scores, only the online versions of Clinical Pharmacology and Micromedex demonstrated superiority over their PDA versions (p>0.01). Online and PDA drug information databases assist practitioners in improving their clinical decision-making. Lexi-Drugs performed significantly better than all of the other PDA databases evaluated. No PDA database demonstrated superiority to its online counterpart; however, the online versions of Clinical Pharmacology and Micromedex were superior to their PDA versions in answering questions.

Accelerant-related burns and drug abuse: Challenging combination.

PubMed

Leung, Leslie T F; Papp, Anthony

2018-05-01

Accelerants are flammable substances that may cause explosion when added to existing fires. The relationships between drug abuse and accelerant-related burns are not well elucidated in the literature. Of these burns, a portion is related to drug manufacturing, which have been shown to be associated with increased burn complications. 1) To evaluate the demographics and clinical outcomes of accelerant-related burns in a Provincial Burn Centre. 2) To compare the clinical outcomes with a control group of non-accelerant related burns. 3) To analyze a subgroup of patients with history of drug abuse and drug manufacturing. Retrospective case control study. Patient data associated with accelerant-related burns from 2009 to 2014 were obtained from the British Columbia Burn Registry. These patients were compared with a control group of non-accelerant related burns. Clinical outcomes that were evaluated include inhalational injury, ICU length of stay, ventilator support, surgeries needed, and burn complications. Chi-square test was used to evaluate categorical data and Student's t-test was used to evaluate mean quantitative data with the p value set at 0.05. A logistic regression model was used to evaluate factors affecting burn complications. Accelerant-related burns represented 28.2% of all burn admissions (N=532) from 2009 to 2014. The accelerant group had higher percentage of patients with history of drug abuse and was associated with higher TBSA burns, ventilator support, ICU stay and pneumonia rates compared to the non-accelerant group. Within the accelerant group, there was no difference in clinical outcomes amongst people with or without history of drug abuse. Four cases were associated with methamphetamine manufacturing, all of which underwent ICU stay and ventilator support. Accelerant-related burns cause significant burden to the burn center. A significant proportion of these patients have history of drug abuse. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

77 FR 76049 - Draft Guidance for Industry on Electronic Source Data in Clinical Investigations; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

..., Office of Planning & Informatics, Center for Drug Evaluation and Research, Food and Drug Administration... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0643...: Food and Drug Administration, HHS. ACTION: Notice; correction. [[Page 76050

Vaginal drug distribution modeling.

PubMed

Katz, David F; Yuan, Andrew; Gao, Yajing

2015-09-15

This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

Cathepsin B Cleavage of vcMMAE-Based Antibody-Drug Conjugate Is Not Drug Location or Monoclonal Antibody Carrier Specific.

PubMed

Gikanga, Benson; Adeniji, Nia S; Patapoff, Thomas W; Chih, Hung-Wei; Yi, Li

2016-04-20

Antibody-drug conjugates (ADCs) require thorough characterization and understanding of product quality attributes. The framework of many ADCs comprises one molecule of antibody that is usually conjugated with multiple drug molecules at various locations. It is unknown whether the drug release rate from the ADC is dependent on drug location, and/or local environment, dictated by the sequence and structure of the antibody carrier. This study addresses these issues with valine-citrulline-monomethylauristatin E (vc-MMAE)-based ADC molecules conjugated at reduced disulfide bonds, by evaluating the cathepsin B catalyzed drug release rate of ADC molecules with different drug distributions or antibody carriers. MMAE drug release rates at different locations on ADC I were compared to evaluate the impact of drug location. No difference in rates was observed for drug released from the V(H), V(L), or C(H)2 domains of ADC I. Furthermore, four vc-MMAE ADC molecules were chosen as substrates for cathepsin B for evaluation of Michaelis-Menten parameters. There was no significant difference in K(M) or k(cat) values, suggesting that different sequences of the antibody carrier do not result in different drug release rates. Comparison between ADCs and small molecules containing vc-MMAE moieties as substrates for cathepsin B suggests that the presence of IgG1 antibody carrier, regardless of its bulkiness, does not impact drug release rate. Finally, a molecular dynamics simulation on ADC II revealed that the val-cit moiety at each of the eight possible conjugation sites was, on average, solvent accessible over 50% of its maximum solvent accessible surface area (SASA) during a 500 ns trajectory. Combined, these results suggest that the cathepsin cleavage sites for conjugated drugs are exposed enough for the enzyme to access and that the drug release rate is rather independent of drug location or monoclonal antibody carrier. Therefore, the distribution of drug conjugation at different sites is not a critical parameter to control in manufacturing of the vc-MMAE-based ADC conjugated at reduced disulfide bonds.

DUE (drug usage evaluation) of ticarcillin and clavulanate potassium: determining appropriate and cost-effective therapeutic options.

PubMed

Lomaestro, B M; Lesar, T S

1988-11-01

The initial 46 patients who were prescribed the combination drug ticarcillin disodium and clavulanate potassium in a 640-bed teaching hospital were evaluated to determine the potential usefulness of the drug in the institution. The review revealed frequent use of the drug for inappropriate indications and in situations for which less expensive antimicrobials were appropriate. The results demonstrate that an increase in costs can occur when an agent that is being considered for formulary addition--because of its cost-saving potential--is not used as expected. In order to optimally utilize the clinical or cost advantages of newer antimicrobials, a program of prescriber education, drug use controls or guidelines, and a concurrent monitoring program may be required and should be implemented at the time of initial drug use within an institution.

Alcohol and drug treatment outcome studies: new methodological review (2005-2010) and comparison with past reviews.

PubMed

Robinson, Sean M; Sobell, Linda Carter; Sobell, Mark B; Arcidiacono, Steven; Tzall, David

2014-01-01

Several methodological reviews of alcohol treatment outcome studies and one review of drug studies have been published over the past 40 years. Although past reviews demonstrated methodological improvements in alcohol studies, they also found continued deficiencies. The current review allows for an updated evaluation of the methodological rigor of alcohol and drug studies and, by utilizing inclusion criteria similar to previous reviews, it allows for a comparative review over time. In addition, this is the first review that compares the methodology of alcohol and drug treatment outcome studies published during the same time period. The methodology for 25 alcohol and 11 drug treatment outcome studies published from 2005 through 2010 that met the review's inclusion criteria was evaluated. The majority of variables evaluated were used in prior reviews. The current review found that more alcohol and drug treatment outcome studies are now using continuous substance use measures and assessing problem severity. Although there have been methodological improvements over time, the current reviews differed little from their most recent past counterpart. Despite this finding, some areas, particularly the continued low reporting of demographic data, needs strengthening. Improvement in the methodological rigor of alcohol and drug treatment outcome studies has occurred over time. The current review found few differences between alcohol and drug study methodologies as well as few differences between the current review and the most recent past alcohol and drug reviews. © 2013 Elsevier Ltd. All rights reserved.

Three Years Evaluation of Drug Shortages from Educational Pharmacies in Tehran

PubMed Central

Gholami, Kheirollah; Kamalinia, Golnaz; Ahmadian Attari, Mohammad Mahdi; Salamzadeh, Jamshid

2012-01-01

The effectiveness of any drug supply systems in providing a trustworthy supply of essential drugs is a critical issue. To evaluate this effectiveness, it is necessary to watch over the status of the essential medicines in any country impartially and continuously. Some countries and also the World Health Organization (WHO) have codified a list of minimum medicines needed for a basic health care system and published them in assortments as a list of essential medicines. The aim of this study was to give an evaluation of the shortages status in Iran and identify the strengths and weaknesses of policies made in Ministry of Health during the years 2005 to 2008 in providing the essential drugs based on the WHO list of essential medicines. The reports used in this retrospective study were collected from the central purchasing unit of one of the main chain drugstores in the country (13-Aban Pharmacy) every 2 to 3 weeks. In these reports, a drug is added to the list of shortages when the requested drug is not delivered. The reports were studied and the results were analyzed based on the WHO list of essential medicines and the national drug list of Iran. The shortages always included 20 to 40 medicines from the list of essential drugs compiled by WHO. Based on this finding, the Ministry of Health and particularly Food and Drug Organization can compile a National List of Essential Medicines and try to always supply them and prevent their shortage. PMID:24250480

Antimicrobial drugs encapsulated in fibrin nanoparticles for treating microbial infested wounds.

PubMed

Alphonsa, B Maria; Sudheesh Kumar, P T; Praveen, G; Biswas, Raja; Chennazhi, K P; Jayakumar, R

2014-05-01

In vitro evaluation of antibacterial and antifungal drugs encapsulated fibrin nanoparticles to prove their potential prospect of using these nanocomponent for effective treatment of microbial infested wounds. Surfactant-free oil-in-water emulsification-diffusion method was adopted to encapsulate 1 mg/ml each of antimicrobial drugs (Ciprofloxacin and Fluconazole) in 4 ml of aqueous fibrinogen suspension and subsequent thrombin mediated cross linking to synthesize drug loaded fibrin nanoparticles. Ciprofloxacin loaded fibrin nanoparticles (CFNPs) showed size range of 253 ± 6 nm whereas that of Fluconazole loaded fibrin nanoparticles (FFNPs) was 260 ± 10 nm. Physico chemical characterizations revealed the firm integration of antimicrobial drugs within fibrin nanoparticles. Drug release studies performed at physiological pH 7.4 showed a release of 16% ciprofloxacin and 8% of fluconazole while as the release of ciprofloxacin at alkaline pH 8.5, was 48% and that of fluconazole was 37%. The antimicrobial activity evaluations of both drug loaded systems independently showed good antibacterial activity against Escherichia coli (E.coli), Staphylococcus aureus (S. aureus) and antifungal activity against Candida albicans (C. albicans). The in vitro toxicity of the prepared drug loaded nanoparticles were further analyzed using Human dermal fibroblast cells (HDF) and showed adequate cell viability. The efficacies of both CFNPs and FFNPs for sustained delivery of encapsulated anti microbial drugs were evaluated in vitro suggesting its potential use for treating microbial infested wounds (diabetic foot ulcer).

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/.

Access to orphan drugs despite poor quality of clinical evidence

PubMed Central

Dupont, Alain G; Van Wilder, Philippe B

2011-01-01

AIM We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence. METHODS Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French ‘Haute Autorité de Santé’, including the five-point scale parameter ‘Service Médical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines. RESULTS Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P = 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease. CONCLUSIONS Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states. PMID:21395641

Quality of life in children with adverse drug reactions: a narrative and systematic review.

PubMed

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-10-01

Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn's disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. © 2014 The British Pharmacological Society.

Quality of life in children with adverse drug reactions: a narrative and systematic review

PubMed Central

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-01-01

Aims Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. Methods We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Results Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn’s disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. Conclusions To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. PMID:24833305

Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.

PubMed

Externbrink, Anna; Eggenreich, Karin; Eder, Simone; Mohr, Stefan; Nickisch, Klaus; Klein, Sandra

2017-01-01

Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of nursing care associated with infants born to mothers with drugs abuse and its comparison with the standards in selected hospitals in Kerman 2013-2014.

PubMed

Mahdavi Khaki, Z; AbbasZadeh, A; Rassoli, M; Zayeri, F

2015-01-01

Background. Pregnancy of women addicted to drugs is a public health problem in most countries, leading to various problems in the mother, the fetus, and the newborn. Since these babies are at risk of various complications and even death, competent and appropriate care of these children is needed. The present study aimed to assess the quality of nursing care provided to newborns and its comparison with the existing standards in infants and neonatal intensive care units of the selected Hospitals in Kerman. Materials and Methods. In this descriptive conducted study, 400 nursing cares, provided to infants born to mothers with drugs abuse, observed and were compared to standard checklists provided by the latest resources and the world's scientific papers. The checklist provided was based on the evaluation of infants and included two distinct categories: non-drug therapy and drug treatment. Finally, the data were analyzed. Results. The consistency quality of the nursing cares provided to infants born to mothers with drugs abuse was evaluated with the existing standards in children, 73% receiving non-drug therapy and 81% of the infants receiving drug treatment. Conclusion. Compared to standards in the normal state, nursing care was associated with babies born to mothers with drugs abuse. The reduction in the incidence of morbidity and mortality in this group of infants was expected in the case of familiarity and training of nursing and the use of caring standards, particularly when applying non-drug therapy.

[Fabrication of a new composite scaffold material for delivering rifampicin and its sustained drug release in rats].

PubMed

Ma, Xue-Ming; Lin, Zhen; Zhang, Jia-Wei; Sang, Chao-Hui; Qu, Dong-Bin; Jiang, Jian-Ming

2016-03-01

To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

[In silico, in vitro, in omic experimental models and drug safety evaluation].

PubMed

Claude, Nancy; Goldfain-Blanc, Françoise; Guillouzo, André

2009-01-01

Over the last few decades, toxicology has benefited from scientific, technical, and bioinformatic developments relating to patient safety assessment during clinical and drug marketing studies. Based on this knowledge, new in silico, in vitro, and "omic" experimental models are emerging. Although these models cannot currently replace classic safety evaluations performed on laboratory animals, they allow compounds with unacceptable toxicity to be rejected in the early stages of drug development, thereby reducing the number of laboratory animals needed. In addition, because these models are particularly adapted to mechanistic studies, they can help to improve the relevance of the data obtained, thus enabling better prevention and screening of the adverse effects that may occur in humans. Much progress remains to be done, especially in the field of validation. Nevertheless, current efforts by industrial, academic laboratories, and regulatory agencies should, in coming years, significantly improve preclinical drug safety evaluation thanks to the integration of these new methods into the drug research and development process.

Interaction of dacarbazine and imexon, in vitro and in vivo, in human A375 melanoma cells.

PubMed

Samulitis, Betty K; Dorr, Robert T; Chow, H-H Sherry

2011-09-01

We evaluated mechanisms of interaction between the alkyating agent dacarbazine (DTIC) and the pro-oxidant, imexon, in the human A375 melanoma cell line. The effect of DTIC and imexon, alone and in combination, was evaluated for growth inhibition (MTT), radiolabeled drug uptake, cellular thiol content (HPLC), and DNA strand breaks (Comet assay). Pharmacokinetic and antitumor effects were evaluated in mice. Growth inhibition in vitro was additive with the two drugs. There was no effect on drug uptake or on the number of DNA strand breaks. There was a >75% reduction in cellular glutathione and cysteine with imexon but not DTIC. Co-administration of the two drugs in mice caused an increase in the area under the curve of both drugs, but the combination was not effective in reducing human A375 melanoma tumors in vivo. Imexon and dacarbazine show additive effects in vitro but not in vivo in human A375 melanoma cells.

The use of mechanistic evidence in drug approval.

PubMed

Aronson, Jeffrey K; La Caze, Adam; Kelly, Michael P; Parkkinen, Veli-Pekka; Williamson, Jon

2018-06-11

The role of mechanistic evidence tends to be under-appreciated in current evidence-based medicine (EBM), which focusses on clinical studies, tending to restrict attention to randomized controlled studies (RCTs) when they are available. The EBM+ programme seeks to redress this imbalance, by suggesting methods for evaluating mechanistic studies alongside clinical studies. Drug approval is a problematic case for the view that mechanistic evidence should be taken into account, because RCTs are almost always available. Nevertheless, we argue that mechanistic evidence is central to all the key tasks in the drug approval process: in drug discovery and development; assessing pharmaceutical quality; devising dosage regimens; assessing efficacy, harms, external validity, and cost-effectiveness; evaluating adherence; and extending product licences. We recommend that, when preparing for meetings in which any aspect of drug approval is to be discussed, mechanistic evidence should be systematically analysed and presented to the committee members alongside analyses of clinical studies. © 2018 The Authors Journal of Evaluation in Clinical Practice Published by John Wiley & Sons Ltd.

Evaluation of the activity of CYP2C19 in Gujrati and Marwadi subjects living in Mumbai (Bombay).

PubMed

Panchabhai, Tanmay S; Noronha, Shaun F; Davis, Sanish; Shinde, Vishal M; Kshirsagar, Nilima A; Gogtay, Nithya J

2006-10-24

Inherited differences in the metabolism and disposition of drugs, and genetic polymorphisms in the targets of drug therapy (e.g., receptors), can greatly influence efficacy and toxicity of medications. Marked interethnic differences in CYP2C19 (a member of the cytochrome P-450 enzyme superfamily catalyzing phase I drug metabolism) which affects the metabolism of a number of clinically important drugs have been documented. The present study evaluated the activity of CYP2C19 in normal, healthy Gujrati and Marwadi subjects by phenotyping (a western Indian population). All subjects received 20 mg of omeprazole, which was followed by blood collection at 3 hrs to estimate the metabolic ratio of omeprazole to 5-hydroxyomeprazole. The analysis was done by HPLC. It was seen that 10.36% of this population were poor metabolizers(PM) whereas 89.63% were extensive metabolizers(EM). A genotyping evaluation would better help in identifying population specific genotypes and thus help individualize drug therapy.

[Nasal submicron emulsion of Scutellariae Radix extract preparation technology research based on phase transfer of solute technology].

PubMed

Shi, Ya-jun; Shi, Jun-hui; Chen, Shi-bin; Yang, Ming

2015-07-01

Based on the demand of nasal drug delivery high drug loadings, using the unique phase transfer of solute, integrating the phospholipid complex preparation and submicron emulsion molding process of Scutellariae Radix extract, the study obtained the preparation of the high drug loadings submicron emulsion of Scutellariae Radix extract. In the study of drug solution dispersion method, the uniformity of drug dispersed as the evaluation index, the traditional mixing method, grinding, homogenate and solute phase transfer technology were investigated, and the solute phase transfer technology was adopted in the last. With the adoption of new technology, the drug loading capacity reached 1.33% (phospholipid complex was 4%). The drug loading capacity was improved significantly. The transfer of solute method and timing were studied as follows,join the oil phase when the volume of phospholipid complex anhydrous ethanol solution remaining 30%, the solute phase transfer was completed with the continued recycling of anhydrous ethanol. After drug dissolved away to oil phase, the preparation technology of colostrum was determined with the evaluation index of emulsion droplet form. The particle size of submicron emulsion, PDI and stability parameters were used as evaluation index, orthogonal methodology were adopted to optimize the submicron emulsion ingredient and main influential factors of high pressure homogenization technology. The optimized preparation technology of Scutellariae Radix extract nasal submicron emulsion is practical and stable.

Evaluation of Asoka Aristha, an indigenous medicine in Sri Lanka.

PubMed

Middelkoop, T B; Labadie, R P

1983-09-01

This paper presents the results of an investigation of Asoka Aristha, an indigenous medicine used in rural Sri Lanka for menstrual disorders. This investigation was part of a broader evaluation of ayurvedic drugs aimed at establishing the botanic identity of drug ingredients, establishing possible modes of action, and identifying the chemical constituents responsible for the drug effects. It is projected that the results of this research can be used to standardize ayurvedic drugs and optimize the quality and production procedures. Asoka Aristha, a fermented potion composed largely of Asoka bark, is produced on a large scale by the state-owned Ayurvedic Drugs Corporation. It has been indicated for women in cases of menorrhagia, metrorrhagia, leukorrhea, primary amenorrhea, general menstrual disorders, and skin disorders. 3 types of experiments are projected to evaluate the biologic activity of Asoka Aristha: measurement of the occurrence of cornification of the uterus epithelium in hypophysectomized rats after administration of the drug to determine the estrogenic mode of action, in vitro measurement of the direct uterine activity of the drug to determinme the oxytocic effect, and testing of the inhibiting properties of the drug in prostaglandin synthetase enzyme reactions in vitro. Experiments carried out on rat uteri so far seem to rule out the mechanism based on oxytocic action. It is urged that clinical trials on the therapeutic effect of Asoka Aristha be carried out in Sri Lanka.

Evaluation and modeling of the eutectic composition of various drug-polyethylene glycol solid dispersions.

PubMed

Baird, Jared A; Taylor, Lynne S

2011-06-01

The purpose of this study was to gain a better understanding of which factors contribute to the eutectic composition of drug-polyethylene glycol (PEG) blends and to compare experimental values with predictions from the semi-empirical model developed by Lacoulonche et al. Eutectic compositions of various drug-PEG 3350 solid dispersions were predicted, assuming athermal mixing, and compared to experimentally determined eutectic points. The presence or absence of specific interactions between the drug and PEG 3350 were investigated using Fourier transform infrared (FT-IR) spectroscopy. The eutectic composition for haloperidol-PEG and loratadine-PEG solid dispersions was accurately predicted using the model, while predictions for aceclofenac-PEG and chlorpropamide-PEG were very different from those experimentally observed. Deviations in the model prediction from ideal behavior for the systems evaluated were confirmed to be due to the presence of specific interactions between the drug and polymer, as demonstrated by IR spectroscopy. Detailed analysis showed that the eutectic composition prediction from the model is interdependent on the crystal lattice energy of the drug compound (evaluated from the melting temperature and the heat of fusion) as well as the nature of the drug-polymer interactions. In conclusion, for compounds with melting points less than 200°C, the model is ideally suited for predicting the eutectic composition of systems where there is an absence of drug-polymer interactions.

Herb-drug interactions: challenges and opportunities for improved predictions.

PubMed

Brantley, Scott J; Argikar, Aneesh A; Lin, Yvonne S; Nagar, Swati; Paine, Mary F

2014-03-01

Supported by a usage history that predates written records and the perception that "natural" ensures safety, herbal products have increasingly been incorporated into Western health care. Consumers often self-administer these products concomitantly with conventional medications without informing their health care provider(s). Such herb-drug combinations can produce untoward effects when the herbal product perturbs the activity of drug metabolizing enzymes and/or transporters. Despite increasing recognition of these types of herb-drug interactions, a standard system for interaction prediction and evaluation is nonexistent. Consequently, the mechanisms underlying herb-drug interactions remain an understudied area of pharmacotherapy. Evaluation of herbal product interaction liability is challenging due to variability in herbal product composition, uncertainty of the causative constituents, and often scant knowledge of causative constituent pharmacokinetics. These limitations are confounded further by the varying perspectives concerning herbal product regulation. Systematic evaluation of herbal product drug interaction liability, as is routine for new drugs under development, necessitates identifying individual constituents from herbal products and characterizing the interaction potential of such constituents. Integration of this information into in silico models that estimate the pharmacokinetics of individual constituents should facilitate prospective identification of herb-drug interactions. These concepts are highlighted with the exemplar herbal products milk thistle and resveratrol. Implementation of this methodology should help provide definitive information to both consumers and clinicians about the risk of adding herbal products to conventional pharmacotherapeutic regimens.

Design and evaluation of effervescent floating tablets based on hydroxyethyl cellulose and sodium alginate using pentoxifylline as a model drug

PubMed Central

Rahim, Safwan Abdel; Carter, Paul A; Elkordy, Amal Ali

2015-01-01

The aim of this work was to design and evaluate effervescent floating gastro-retentive drug delivery matrix tablets with sustained-release behavior using a binary mixture of hydroxyethyl cellulose and sodium alginate. Pentoxifylline was used as a highly water-soluble, short half-life model drug with a high density. The floating capacity, swelling, and drug release behaviors of drug-loaded matrix tablets were evaluated in 0.1 N HCl (pH 1.2) at 37°C±0.5°C. Release data were analyzed by fitting the power law model of Korsmeyer–Peppas. The effect of different formulation variables was investigated, such as wet granulation, sodium bicarbonate gas-forming agent level, and tablet hardness properties. Statistical analysis was applied by paired sample t-test and one-way analysis of variance depending on the type of data to determine significant effect of different parameters. All prepared tablets through wet granulation showed acceptable physicochemical properties and their drug release profiles followed non-Fickian diffusion. They could float on the surface of dissolution medium and sustain drug release over 24 hours. Tablets prepared with 20% w/w sodium bicarbonate at 50–54 N hardness were promising with respect to their floating lag time, floating duration, swelling ability, and sustained drug release profile. PMID:25848220

Herb–Drug Interactions: Challenges and Opportunities for Improved Predictions

PubMed Central

Brantley, Scott J.; Argikar, Aneesh A.; Lin, Yvonne S.; Nagar, Swati

2014-01-01

Supported by a usage history that predates written records and the perception that “natural” ensures safety, herbal products have increasingly been incorporated into Western health care. Consumers often self-administer these products concomitantly with conventional medications without informing their health care provider(s). Such herb–drug combinations can produce untoward effects when the herbal product perturbs the activity of drug metabolizing enzymes and/or transporters. Despite increasing recognition of these types of herb–drug interactions, a standard system for interaction prediction and evaluation is nonexistent. Consequently, the mechanisms underlying herb–drug interactions remain an understudied area of pharmacotherapy. Evaluation of herbal product interaction liability is challenging due to variability in herbal product composition, uncertainty of the causative constituents, and often scant knowledge of causative constituent pharmacokinetics. These limitations are confounded further by the varying perspectives concerning herbal product regulation. Systematic evaluation of herbal product drug interaction liability, as is routine for new drugs under development, necessitates identifying individual constituents from herbal products and characterizing the interaction potential of such constituents. Integration of this information into in silico models that estimate the pharmacokinetics of individual constituents should facilitate prospective identification of herb–drug interactions. These concepts are highlighted with the exemplar herbal products milk thistle and resveratrol. Implementation of this methodology should help provide definitive information to both consumers and clinicians about the risk of adding herbal products to conventional pharmacotherapeutic regimens. PMID:24335390

Osmotic pellet system comprising osmotic core and in-process amorphized drug in polymer-surfactant layer for controlled delivery of poorly water-soluble drug.

PubMed

Saindane, Nilesh; Vavia, Pradeep

2012-09-01

The aim of the present investigation was to develop controlled porosity osmotic system for poorly water-soluble drug based on drug in polymer-surfactant layer technology. A poorly water-soluble drug, glipizide (GZ), was selected as the model drug. The technology involved core of the pellets containing osmotic agent coated with drug dispersed in polymer and surfactant layer, finally coated with release-retardant layer with pore former. The optimized drug-layer-coated pellets were evaluated for solubility of GZ at different pH conditions and characterized for amorphous nature of the drug by differential scanning calorimetry and X-ray powder diffractometry. The optimized release-retardant layer pellets were evaluated for in vitro drug release at different pH, hydrodynamic, and osmolality conditions. The optimized drug layer showed improvement in solubility (10 times in pH 1.2, 11 times in pH 4.5, and 21 times in pH 6.8), whereas pellets coated with cellulose acetate (15.0%, w/w, weight gain) with pore former triethyl citrate (10.0%, w/w, of polymer) demonstrated zero-order drug release for 24 h at different pH conditions; moreover, retardation of drug release was observed with increment of osmolality. This system could be a platform technology for controlled delivery of poorly water-soluble drugs. Copyright © 2012 Wiley Periodicals, Inc.

Personal digital assistant-based drug information sources: potential to improve medication safety.

PubMed

Galt, Kimberly A; Rule, Ann M; Houghton, Bruce; Young, Daniel O; Remington, Gina

2005-04-01

This study compared the potential for personal digital assistant (PDA)-based drug information sources to minimize potential medication errors dependent on accurate and complete drug information at the point of care. A quality and safety framework for drug information resources was developed to evaluate 11 PDA-based drug information sources. Three drug information sources met the criteria of the framework: Eprocrates Rx Pro, Lexi-Drugs, and mobileMICROMEDEX. Medication error types related to drug information at the point of care were then determined. Forty-seven questions were developed to test the potential of the sources to prevent these error types. Pharmacists and physician experts from Creighton University created these questions based on the most common types of questions asked by primary care providers. Three physicians evaluated the drug information sources, rating the source for each question: 1=no information available, 2=some information available, or 3 = adequate amount of information available. The mean ratings for the drug information sources were: 2.0 (Eprocrates Rx Pro), 2.5 (Lexi-Drugs), and 2.03 (mobileMICROMEDEX). Lexi-Drugs was significantly better (mobileMICROMEDEX t test; P=0.05; Eprocrates Rx Pro t test; P=0.01). Lexi-Drugs was found to be the most specific and complete PDA resource available to optimize medication safety by reducing potential errors associated with drug information. No resource was sufficient to address the patient safety information needs for all cases.

Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

PubMed

Rygg, Alex; Hindle, Michael; Longest, P Worth

2016-04-01

The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

Need for multicriteria evaluation of generic drug policies.

PubMed

Kaló, Zoltán; Holtorf, Anke-Peggy; Alfonso-Cristancho, Rafael; Shen, Jie; Ágh, Tamás; Inotai, András; Brixner, Diana

2015-03-01

Policymakers tend to focus on improving patented drug policies because they are under pressure from patients, physicians, and manufacturers to increase access to novel therapies. The success of pharmaceutical innovation over the last few decades has led to the availability of many off-patent drugs to treat disease areas with the greatest public health need. Therefore, the success of public health programs in improving the health status of the total population is highly dependent on the efficiency of generic drug policies. The objective of this article was to explore factors influencing the true efficiency of generic prescription drug policies in supporting public health initiatives in the developed world. Health care decision makers often assess the efficiency of generic drug policies by the level of price erosion and market share of generics. Drug quality, bioequivalence, in some cases drug formulations, supply reliability, medical adherence and persistence, health outcomes, and nondrug costs, however, are also attributes of success for generic drug policies. Further methodological research is needed to measure and improve the efficiency of generic drug policies. This also requires extension of the evidence base of the impact of generic drugs, partly based on real-world evidence. Multicriteria decision analysis may assist policymakers and researchers to evaluate the true value of generic drugs. Copyright © 2015. Published by Elsevier Inc.

Mapping and Analyzing Stakeholders in China's Essential Drug System by Using a Circular Model: Who We Should Deal with Next?

PubMed

Shao, Hui; Li, Shixue; Xu, Lingzhong; Yang, Shuang; Thomas, Nicholas J; Mir, Mohammed Umer; Guo, Zhen; Ning, Bo; Shi, Lizheng

2015-05-01

To predict the prospects of the essential drug system by using the Stakeholder Impact Index (SII) and evaluate the current performance of each main stakeholder and suggested dangerous stakeholders and dormant stakeholders. A Delphi method was used, involving 36 experts with experience in implementation and evaluation of the essential drug policy, to construct the circular model as well as evaluate the performance of each stakeholder. The central government was a dominant stakeholder of the whole essential drug system. The provincial governments were definitive stakeholders, whereas local governments and medical institutions were dependent stakeholders. Furthermore, media and drug stores were dormant stakeholders and pharmaceutical manufacturers and delivery enterprises were dangerous stakeholders. Patients, community residents, and medical insurance programs were discretionary stakeholders. The SII for the essential drug system was positive (SII proj ⁎ = 2.72). The overall anticipation of the essential drug policy is optimistic. Letting definitive stakeholders (provincial governments) having more autonomy can efficiently accelerate the pace of implementation of the essential drug policy in the current situation. Central government, however, also needs to construct an experience exchange platform with the aim of building versatile methods for running the essential drug system in all provinces. Pharmaceutical manufacturers and delivery enterprises were dangerous stakeholders for the essential drug policy. Because of their potential threat to the implementation of the policy, the central government should motivate them to support the construction of the essential drug system spontaneously. In that case, provincial governments need to construct a fair, balanced, and self-stabilized bidding platform. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Hypoglycaemic complications with diabetes mellitus management: the predominant adverse drug reaction presenting to the Accident and Emergency Department of The University Hospital of the West Indies.

PubMed

Gossell-Williams, M; Williams-Johnson, J; Francis, L

2010-10-01

Evaluation of adverse drug reactions (ADRs) is important to the assessment of risk factors in an aim to ensure maximum benefits of drug therapy. This study was done to assess the types of ADRs presenting to the Accident and Emergency department (A&E) of the University Hospital of the West Indies. Admissions to the A&E associated with drugs were followed on a weekly basis for 19 weeks from October 2007 to February 2008 using the patient logbook. Medical records of patients with suspected ADRs were collected and evaluated by an Emergency Medicine Consultant of A & E to confirm the occurrence of ADRs and the suspected drug. Of the 8170 admissions to A&E, 48 (0.6%) were related to ADRs, with most occurring in females and the mean age (+/- standard error) was 58.9 (+/- 3.4) years. Drug induced hypoglycaemia accounted for 28 (56.3%) cases of ADRs and included mainly patients on insulin, with or without a sulphonylurea therapy. Most of these diabetic patients also had co-morbidities and were on multi-drug therapy (18). Allergic reactions accounted for 10 (21%) of the ADR outcomes. Other drugs accounting for ADRs included cardiovascular drugs (10.4%), analgesic/anti-inflammatory medications (8.3%), drugs acting on the central nervous system (8.3%) and anti-infectives (8.3%). It is concluded that drug-induced hypoglycaemia is the major ADR presenting to the A&E of the University Hospital of the West Indies; it is a preventable ADR and therefore further investigation should evaluate possible factors attributed to the occurrences.

An experimental evaluation of drug-induced mutational meltdown as an antiviral treatment strategy.

PubMed

Bank, Claudia; Renzette, Nicholas; Liu, Ping; Matuszewski, Sebastian; Shim, Hyunjin; Foll, Matthieu; Bolon, Daniel N A; Zeldovich, Konstantin B; Kowalik, Timothy F; Finberg, Robert W; Wang, Jennifer P; Jensen, Jeffrey D

2016-11-01

The rapid evolution of drug resistance remains a critical public health concern. The treatment of influenza A virus (IAV) has proven particularly challenging, due to the ability of the virus to develop resistance against current antivirals and vaccines. Here, we evaluate a novel antiviral drug therapy, favipiravir, for which the mechanism of action in IAV involves an interaction with the viral RNA-dependent RNA polymerase resulting in an effective increase in the viral mutation rate. We used an experimental evolution framework, combined with novel population genetic method development for inference from time-sampled data, to evaluate the effectiveness of favipiravir against IAV. Evaluating whole genome polymorphism data across 15 time points under multiple drug concentrations and in controls, we present the first evidence for the ability of IAV populations to effectively adapt to low concentrations of favipiravir. In contrast, under high concentrations, we observe population extinction, indicative of mutational meltdown. We discuss the observed dynamics with respect to the evolutionary forces at play and emphasize the utility of evolutionary theory to inform drug development. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Demystifying the U.S. Food and Drug Administration: I. Understanding agency structure and function.

PubMed

Levi, Benjamin; Lisiecki, Jeffrey; Rubin, Peter; D'Amico, Richard A; Hume, Keith M; Seward, Bill; Cederna, Paul S

2014-06-01

The U.S. Food and Drug Administration is the government agency responsible for oversight of the safety and efficacy of pharmaceuticals and devices, including biologics and devices that combine biologics with other materials. Within the U.S. Food and Drug Administration, the Center for Biologics Evaluation and Research is specifically responsible for the evaluation and approval of biological products. This department of the U.S. Food and Drug Administration has a series of mechanisms in place to aid researchers in the process of developing new biologics. This article outlines the study phases involved in developing new biologics and how the Center for Biologics Evaluation and Research and investigators can work together to facilitate this process. It also discusses issues specific to biologics that have been encountered in the past and that investigators should consider when developing and obtaining approval for new biologics. The equivalent center within the U.S. Food and Drug Administration for approving medical devices is the Center for Devices and Radiological Health. The equivalent process of development and approval of medical devices is similarly discussed. Finally, essential contacts for investigators within the Center for Biologics Evaluation and Research and the Center for Devices and Radiological Health are provided.

Enhancement of oral bioavailability of atorvastatin calcium by self-emulsifying drug delivery systems (SEDDS).

PubMed

Kadu, Pawan J; Kushare, Sachin S; Thacker, Dhaval D; Gattani, Surendra G

2011-02-01

The aim of the present study was to formulate a self-emulsifying drug delivery system of atorvastatin calcium and its characterization including in vitro and in vivo potential. The solubility of atorvastatin calcium was determined in various vehicles such as Captex 355, Captex 355 EP/NF, Ethyl oleate, Capmul MCM, Capmul PG-8, Gelucire 44/14, Tween 80, Tween 20, and PEG 400. Pseudoternary phase diagrams were plotted on the basis of solubility data of drug in various components to evaluate the microemulsification region. Formulation development and screening was carried out based on results obtained from phase diagrams and characteristics of resultant microemulsion. Prepared formulations were tested for microemulsifying properties and evaluated for clarity, precipitation, viscosity determination, drug content and in vitro dissolution. The optimized formulation further evaluated for particle size distribution, zeta potential, stability studies and in vivo potential. In vivo performance of the optimized formulation was evaluated using a Triton-induced hypercholesterolemia model in male Albino Wistar rats. The formulation significantly reduced serum lipid levels as compared with atorvastatin calcium. Thus studies illustrated the potential use for the delivery of hydrophobic drug such as atorvastatin calcium by oral route.

Evaluation of an online injecting drug use stigma intervention targeted at health providers in New South Wales, Australia

PubMed Central

Brener, Loren; Cama, Elena; Hull, Peter; Treloar, Carla

2017-01-01

People who inject drugs are highly stigmatised. Discriminatory experiences are commonly reported, particularly in health care settings. This article evaluates an online stigma reduction training module targeting health providers working with people who inject drugs. A total of 139 participants completed a pre- and post-survey including attitude items and items depicting hypothetical scenarios and concerns around client behaviours. Participants’ attitudes towards people who inject drugs were more positive and they showed less concerns about client behaviours after completing the online training module. Findings highlight the benefits of online training in reducing discriminatory attitudes towards people who inject drugs and improving confidence in working with this client group. PMID:28567299

THE EFFECTIVENESS OF COMPULSORY DRUG TREATMENT: A SYSTEMATIC REVIEW

PubMed Central

Werb, D; Kamarulzaman, A; Meacham, MC; Rafful, C; Fisher, B; Strathdee, SA; Wood, E

2016-01-01

Background Despite widespread implementation of compulsory treatment modalities for drug dependence, there has been no systematic evaluation of the scientific evidence on the effectiveness of compulsory drug treatment. Methods We conducted a systematic review of studies assessing the outcomes of compulsory treatment. We conducted a search in duplicate of all relevant peer-reviewed scientific literature evaluating compulsory treatment modalities. The following academic databases were searched: PubMed, PAIS International, Proquest, PsycINFO, Web of Science, Soc Abstracts, JSTOR, EBSCO/Academic Search Complete, REDALYC, SciELO Brazil. We also searched the Internet, and article reference lists, from database inception to July 15th, 2015. Eligibility criteria are as follows: peer-reviewed scientific studies presenting original data. Primary outcome of interest was post-treatment drug use. Secondary outcome of interest was post-treatment criminal recidivism. Results Of an initial 430 potential studies identified, nine quantitative studies met the inclusion criteria. Studies evaluated compulsory treatment options including drug detention facilities, short (i.e. 21-day) and long-term (i.e., 6 months) inpatient treatment, community-based treatment, group-based outpatient treatment, and prison-based treatment. Three studies (33%) reported no significant impacts of compulsory treatment compared with control interventions. Two studies (22%) found equivocal results but did not compare against a control condition. Two studies (22%) observed negative impacts of compulsory treatment on criminal recidivism. Two studies (22%) observed positive impacts of compulsory inpatient treatment on criminal recidivism and drug use. Conclusion There is limited scientific literature evaluating compulsory drug treatment. Evidence does not, on the whole, suggest improved outcomes related to compulsory treatment approaches, with some studies suggesting potential harms. Given the potential for human rights abuses within compulsory treatment settings, non-compulsory treatment modalities should be prioritized by policymakers seeking to reduce drug-related harms. PMID:26790691

What criteria for pharmaceuticals reimbursement? An empirical analysis of the evaluation of "medical service rendered" by reimbursable drugs in France.

PubMed

Le Pen, C; Priol, G; Lilliu, H

2003-01-01

The criteria for the registration of new drugs may differ from the criteria for drug reimbursement. In 2000 the French government entrusted the French Medicines Agency with determining the "medical service rendered" (MSR) for each reimbursable drug. The goal was to determine which drugs could be classified with an "insufficient" MSR and therefore should be taken out of the scope of health insurance. We analyze the concepts and methods used for this evaluation and the kind of results that are obtained. We collected data on the result of MSR classification and the criteria used to perform this classification (efficacy-security, severity of the disease,place in the therapeutic strategy, existence of therapeutic alternative, public health value) for a sample of 1453 drugs belonging to five therapeutic areas. We used statistical analysis to determine what were the most influential criteria. Only two criteria - efficacy and disease severity - suffice to very largely explain the MSR classification. The other criteria contribute little added value. Some of these criteria clearly suffer from a lack of clarification, leading to different interpretations according to therapeutic class or even according to drug or drug family. The evaluation procedure differs between therapeutic classes, at least at intermediate MSR levels. Analysis of the French experience with MSR shows that the evaluation procedure has not succeeded in completely breaking away from the traditional logic of the marketing authorization and registration, as witnessed by the importance of the "efficacy/safety" criterion, the absence of an economic criterion, and the vagueness of the "public health value" criterion, which one would have thought would instead be decisive.

76 FR 78931 - Advisory Committees; Tentative Schedule of Meetings for 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-20

... FOR BIOLOGICS EVALUATION AND RESEARCH Allergenic Products Advisory Committee. April 18, October 18...- 15. CENTER FOR DRUG EVALUATION AND RESEARCH Anesthetic and Analgesic Drugs Advisory February 9...-6. Ophthalmic Devices Panel November 8-9. Orthopedic and Rehabilitation Devices September 13-14...

77 FR 13131 - Advisory Committees; Filing of Closed Meeting Reports

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-05

..., 2010 through September 30, 2011: Center for Biologics Evaluation and Research Allergenic Products... Vaccines and Related Biological Products Advisory Committee Center for Drug Evaluation and Research... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001...

[Evaluation of the effectiveness of a prison-based drug treatment].

PubMed

Casares-López, María José; González-Menéndez, Ana M; Fernández-García, M Paula; Villagrá, Patricia

2012-05-01

The present study evaluated the effectiveness of a drug-free unit (DFU) in reducing the use of substances by incarcerated adult offenders, and to analyze changes in the addiction severity index, motivation, and personality caused by the program. This is an external evaluation, with an ex post facto design with repeated measures. Eighty-seven prisoners from the DFU were evaluated during the first year of residence in the program. Most are young men, polydrug addicts and mainly serving sentences for public health crimes and property offenses. There is need of psychiatric treatment at the baseline, with 85% comorbid personality disorders. Motivation for treatment is low, and remains stable over 12 month's duration of the study. The DFU was found to have a significant effect in reducing the use of drugs by offenders and to improve the drug and family composite scores, also reducing scores on personality scales. However, it fails to change medical and psychiatric scores, so that the need for intervention in these areas is underscored.

Evaluation of a peer-led drug abuse risk reduction project for runaway/homeless youths.

PubMed

Fors, S W; Jarvis, S

1995-01-01

The purpose of this study was to evaluate the Drug Prevention in Youth risk reduction program that was implemented in shelters for runaway/homeless youths in the Southeastern United States. The program focuses on knowledge, attitudes and skills that can help this group of high risk young people minimize the serious negative consequences of drug abuse. An evaluation strategy was developed so comparisons could be made between peer-led, adult-led and non-intervention groups. Dependent samples t tests and least squares ANCOVAS were used to measure pretest-posttest differences both within and between groups. Results indicate that the peer-led groups were more successful than the other two groups, and that program effects were the most powerful with the youngest group of shelter clients. Process evaluation revealed important factors related to group leader training and group management. It is concluded that well-trained and motivated peer/near peer leaders have particularly valuable contributions to make with regard to drug abuse risk reduction for shelter clients.

Evaluation of intestinal metabolism and absorption using the Ussing chamber system equipped with intestinal tissue from rats and dogs.

PubMed

Miyake, Masateru; Kondo, Satoshi; Koga, Toshihisa; Yoda, Noriaki; Nakazato, Satoru; Emoto, Chie; Mukai, Tadashi; Toguchi, Hajime

2018-01-01

The purpose of this study was to evaluate the intestinal metabolism and absorption in a mini-Ussing chamber equipped with animal intestinal tissues, based on the transport index (TI). TI value was defined as the sum of drug amounts transported to the basal-side component (X corr ) and drug amounts accumulated in the tissue (T corr ), which are normalized by AUC of a drug in the apical compartment, as an index for drug absorption. Midazolam was used as a test compound for the evaluation of intestinal metabolism and absorption. The metabolite formulation of midazolam was observed in both rats and dogs. Ketoconazole inhibited the intestinal metabolism of midazolam in rats and improved its intestinal absorption to a statistically significant extent. Therefore, the mini-Ussing chamber, equipped with animal intestinal tissues, showed potential to use the evaluation of the intestinal metabolism and absorption, including the assessment of species differences. Copyright © 2017. Published by Elsevier B.V.

Evaluation of a Perforated Drug Delivery System in Mice for Prolonged and Constant Release of a Hydrophilic Drug

DTIC Science & Technology

2012-02-17

A drug delivery system (DDS) consisting of a perforated microtube ( polyimide , inside diameter= 1.8 mm, tube length= 20 mm, hole size= 0.15 mm) was... biocompatible and capable of long-term constant release of hydrophilic drugs such as sodium fluorescein.

78 FR 70248 - Medical Gas Regulation Review; Announcement of Public Meeting; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

...: [email protected] ; or Christine Kirk, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket No...: Food and Drug Administration, HHS. ACTION: Notice of public meeting; correction. SUMMARY: The Food and...

75 FR 60432 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... the youth's drug use, attitudes, and knowledge, as well as factors such as self-esteem by... (this is not a toll-free number). Title and OMB Number: Evaluation of Young Marines Drug Education..., the Young Marines, in reducing drug use and promoting a healthy, drug- free lifestyle among its youth...

21 CFR 312.145 - Guidance documents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Miscellaneous § 312.145 Guidance documents. (a) FDA has... of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002. A request for a copy of the CBER list should be directed to...

21 CFR 312.145 - Guidance documents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Miscellaneous § 312.145 Guidance documents. (a) FDA has... of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002. A request for a copy of the CBER list should be directed to...

21 CFR 312.145 - Guidance documents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Miscellaneous § 312.145 Guidance documents. (a) FDA has... of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002. A request for a copy of the CBER list should be directed to...

21 CFR 312.145 - Guidance documents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Miscellaneous § 312.145 Guidance documents. (a) FDA has... of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002. A request for a copy of the CBER list should be directed to...

10 CFR 712.14 - Medical assessment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... abuse of legal drugs or other substances, as identified by self-reporting or by medical or psychological... use disorder, use of illegal drugs, or the abuse of legal drugs or other substances, must undergo an... psychiatric evaluations, a review of current legal drug use, and any other relevant information. This...

75 FR 10806 - Training Program for Regulatory Project Managers; Information Available to Industry

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0108] Training Program for Regulatory Project Managers; Information Available to Industry AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) Center for Drug Evaluation...

Enhancing Residential Treatment for Drug Court Participants

ERIC Educational Resources Information Center

Koob, Jeff; Brocato, Jo; Kleinpeter, Christine

2011-01-01

In this study, the authors describe and evaluate the impact of increased access to residential treatment added to traditional drug court services in Orange County, California, with a goal of increasing program retention, successful completion, and graduation rates for a high-risk drug offender population participating in drug court between January…

21 CFR 207.37 - Inspection of registrations and drug listings.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Management Team (HFD-095), Office of Information Technology, Center for Drug Evaluation and Research, Food... information submitted under the drug listing requirements will be available for public disclosure when...) Information that has become a matter of public knowledge. (x) A list of drug products containing a particular...

76 FR 18558 - Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Exception From...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

... Sponsors: Exception From Informed Consent for Emergency Research; Availability AGENCY: Food and Drug... oversight of research involving FDA-regulated products (e.g., drugs, biological products, devices) in..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51...

76 FR 52334 - Arthritis Advisory Committee; Notice of Postponement of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-22

...: Philip A. Bautista, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Arthritis Advisory Committee; Notice of Postponement of Meeting AGENCY: Food and Drug Administration, HHS...

21 CFR 864.9050 - Blood bank supplies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Biologics Evaluation and Research of the Food and Drug Administration. (b) Classification. Class I (general... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood bank supplies. 864.9050 Section 864.9050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 640.103 - The final product.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false The final product. 640.103 Section 640.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... manufacturer by the Director, Center for Biologics Evaluation and Research, Food and Drug Administration. [38...

21 CFR 26.4 - Product coverage.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Products regulated by the Food and Drug Administration's Center for Biologics Evaluation and Research or... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Product coverage. 26.4 Section 26.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF...

21 CFR 26.4 - Product coverage.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Products regulated by the Food and Drug Administration's Center for Biologics Evaluation and Research or... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Product coverage. 26.4 Section 26.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF...

21 CFR 864.9050 - Blood bank supplies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Biologics Evaluation and Research of the Food and Drug Administration. (b) Classification. Class I (general... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Blood bank supplies. 864.9050 Section 864.9050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 640.103 - The final product.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true The final product. 640.103 Section 640.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... manufacturer by the Director, Center for Biologics Evaluation and Research, Food and Drug Administration. [38...

What is prescription labeling communicating to doctors about hepatotoxic drugs? A study of FDA approved product labeling.

PubMed

Willy, Mary E; Li, Zili

2004-04-01

The objective of this study was to evaluate the informativeness and consistency of product labeling of hepatotoxic drugs marketed in the United States. We searched the Physicians' Desk Reference-2000 for prescription drugs with hepatic failure and/or hepatic necrosis listed in the labeling. We used a six-item checklist to evaluate the 'informativeness' and consistency of the labeling content. An informativeness score equaled the proportion of checklist items present in each drug's labeling. Ninety-five prescription drugs were included in the study. Eleven (12%) of the drugs had information related to hepatic failure in a Black Boxed Warning, 52 (54%) in the Warnings section and 32 (34%) in the Adverse Reactions section of the label. The mean informativeness score was 35%; the score was significantly higher, 61%, when the risk was perceived to be high. The informativeness of labeling was not affected by the time of the labeling, but differed across the Center for Drug Evaluation and Research (CDER) Review Division responsible for the labeling. The information provided in labeling is variable and affected by many factors, including the perceived level of risk and review division strategy. Product labeling may benefit from current FDA initiatives to improve the consistency of risk-related labeling.

[Evaluation of Gastric Mucosal Injury Model Animals of Rebamipide Formulation--Study of Therapeutic Equivalence].

PubMed

Abe, Noriaki; Funato, Hiroki; Hirata, Ayumu; Nakai, Megumi; Iizuka, Michiro; Shiraishi, Hisashi; Jobu, Kohei; Yagi, Yusuke; Kadota, Aki; Ogi, Kyoko; Yokota, Junko; Miyamura, Mitsuhiko

2016-01-01

The introduction of generic drugs is promoted from the perspective of medical economics. In this context, we need to understand not only the bioequivalence of generic drugs specified in "the Guidelines for Bioequivalence Studies of Generic Products", but also formulation properties to consider their effect on pharmacological therapy. We evaluated the pharmaceutical characteristics of rebamipide formulations, a brand-name drug and two generic drugs, and their clinical functionality by using rat models of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Pharmaceutical evaluation showed significant differences in hardness. The inter-lot variation was small in all rebamipide formulations. In the clinical functionality study, biochemistry test values 7 d after the administration of rebamipide showed no differences among formulations. Higher levels of mucosal fluid secretion and antioxidative enzymes were observed in the groups administered rebamipide than in the control group. The levels of lipid peroxide were lower in the groups administered rebamipide than the control group. Multivariate analysis showed slight divergence between the brand-name and generic drugs. In future, it will be necessary to select generic drugs after careful consideration of bioequivalence, clinical functionality, and therapeutic equivalence by reviewing scientific evidence such as indication and formulation design, not to mention stable provision.

Compressibility of binary powder formulations: investigation and evaluation with compaction equations.

PubMed

Gentis, Nicolaos D; Betz, Gabriele

2012-02-01

The purpose of this work was to investigate and evaluate the powder compressibility of binary mixtures containing a well-compressible compound (microcrystalline cellulose) and a brittle active drug (paracetamol and mefenamic acid) and its progression after a drug load increase. Drug concentration range was 0%-100% (m/m) with 10% intervals. The powder formulations were compacted to several relative densities with the Zwick material tester. The compaction force and tensile strength were fitted to several mathematical models that give representative factors for the powder compressibility. The factors k and C (Heckel and modified Heckel equation) showed mostly a nonlinear correlation with increasing drug load. The biggest drop in both factors occurred at far regions and drug load ranges. This outcome is crucial because in binary mixtures the drug load regions with higher changeover of plotted factors could be a hint for an existing percolation threshold. The susceptibility value (Leuenberger equation) showed varying values for each formulation without the expected trend of decrease for higher drug loads. The outcomes of this study showed the main challenges for good formulation design. Thus, we conclude that such mathematical plots are mandatory for a scientific evaluation and prediction of the powder compaction process. Copyright © 2011 Wiley Periodicals, Inc.

Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in HIPEC.

PubMed

Mas-Fuster, Maria Isabel; Ramon-Lopez, Amelia; Lacueva, Javier; Más-Serrano, Patricio; Nalda-Molina, Ricardo

2018-02-01

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Compendia and anticancer therapy under Medicare.

PubMed

Tillman, Katherine; Burton, Brijet; Jacques, Louis B; Phurrough, Steve E

2009-03-03

In 1993, Congress directed the Medicare program to refer to 3 existing published compendia, American Medical Association Drug Evaluations (AMA-DE), United States Pharmacopoeia Drug Information for the Health Professional (USP-DI), and American Hospital Formulary Service Drug Information (AHFS-DI), to identify unlabeled but medically accepted uses of drugs and biologicals in anticancer chemotherapy regimens. Public discussion during the preceding years had centered on whether to designate unlabeled uses of anticancer treatments as experimental and thus outside the scope of Medicare benefits. American Medical Association Drug Evaluations and USP-DI subsequently ceased publication, and the Medicare program faced increasing calls to revise the list of acceptable compendia, as authorized in the statute. In 2007, the Centers for Medicare & Medicaid Services used its regulatory authority to establish a publicly transparent process to revise the list. The Centers for Medicare & Medicaid Services considered 5 requests in 2008 and added National Comprehensive Cancer Network Drugs and Biologics Compendium, DRUGDEX, and Clinical Pharmacology to the list of compendia. DrugPoints was not added, and AMA-DE was removed. Because of the potential for conflicts of interest to lead to biased judgments, the 2008 Medicare Improvements for Patients and Providers Act has a provision that explicitly prohibits inclusion of compendia that do not have a publicly transparent process for evaluating therapies and identifying potential conflicts of interest.

In vitro transcriptomic prediction of hepatotoxicity for early drug discovery

PubMed Central

Cheng, Feng; Theodorescu, Dan; Schulman, Ira G.; Lee, Jae K.

2012-01-01

Liver toxicity (hepatotoxicity) is a critical issue in drug discovery and development. Standard preclinical evaluation of drug hepatotoxicity is generally performed using in vivo animal systems. However, only a small number of preselected compounds can be examined in vivo due to high experimental costs. A more efficient yet accurate screening technique which can identify potentially hepatotoxic compounds in the early stages of drug development would thus be valuable. Here, we develop and apply a novel genomic prediction technique for screening hepatotoxic compounds based on in vitro human liver cell tests. Using a training set of in vivo rodent experiments for drug hepatotoxicity evaluation, we discovered common biomarkers of drug-induced liver toxicity among six heterogeneous compounds. This gene set was further triaged to a subset of 32 genes that can be used as a multi-gene expression signature to predict hepatotoxicity. This multi-gene predictor was independently validated and showed consistently high prediction performance on five test sets of in vitro human liver cell and in vivo animal toxicity experiments. The predictor also demonstrated utility in evaluating different degrees of toxicity in response to drug concentrations which may be useful not only for discerning a compound’s general hepatotoxicity but also for determining its toxic concentration. PMID:21884709

Does Drug Testing Deter Drug Court Participants from Using Drugs or Alcohol?

ERIC Educational Resources Information Center

Kleinpeter, Christine B.; Brocato, Jo; Koob, Jeffrey J.

2010-01-01

This study evaluates 3 drug-testing strategies implemented in 5 different jurisdictions with drug courts in Orange County, California. The purpose of the study was to determine whether the sweat patch acts as a deterrent and under what conditions it can be used to improve outcomes. Results indicated that although the use of the sweat patch did not…

A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.

PubMed

Zhou, Shu; Li, Guo-Bo; Huang, Lu-Yi; Xie, Huan-Zhang; Zhao, Ying-Lan; Chen, Yu-Zong; Li, Lin-Li; Yang, Sheng-Yong

2014-08-01

Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of pharmacoeconomics in prescribing research. Part 1: costs--moving beyond the acquisition price for drugs.

PubMed

Robertson, J; Lang, D; Hill, S

2003-02-01

This paper addresses pharmacoeconomics in prescribing research and reflects the increasing use of techniques of economic evaluation to aid drug purchasing decisions in a variety of settings -- for national drug subsidization programmes, provincial purchasing plans, insurance programmes, and for hospital and area health authority formulary decisions. First, we focus on the cost component of an economic evaluation and discuss methodological issues that are relevant to all pharmacoeconomic analyses.

Polymeric Precipitation Inhibitors Promote Fenofibrate Supersaturation and Enhance Drug Absorption from a Type IV Lipid-Based Formulation.

PubMed

Suys, Estelle J A; Chalmers, David K; Pouton, Colin W; Porter, Christopher J H

2018-06-04

The ability of lipid-based formulations (LBFs) to increase the solubilization, and prolong the supersaturation, of poorly water-soluble drugs (PWSDs) in the gastrointestinal (GI) fluids has generated significant interest in the past decade. One mechanism to enhance the utility of LBFs is to prolong supersaturation via the addition of polymers that inhibit drug precipitation (polymeric precipitation inhibitors or PPIs) to the formulation. In this work, we have evaluated the performance of a range of PPIs and have identified PPIs that are sufficiently soluble in LBF to allow the construction of single phase formulations. An in vitro model was first employed to assess drug (fenofibrate) solubilization and supersaturation on LBF dispersion and digestion. An in vitro-in situ model was subsequently employed to simultaneously evaluate the impact of PPI enhanced drug supersaturation on drug absorption in rats. The stabilizing effect of the polymers was polymer specific and most pronounced at higher drug loads. Polymers that were soluble in LBF allowed simple processing as single phase formulations, while formulations containing more hydrophilic polymers required polymer suspension in the formulation. The lipid-soluble polymers Eudragit (EU) RL100 and poly(propylene glycol) bis(2-aminopropyl ether) (PPGAE) and the water-soluble polymer hydroxypropylmethyl cellulose (HPMC) E4M were identified as the most effective PPIs in delaying fenofibrate precipitation in vitro. An in vitro model of lipid digestion was subsequently coupled directly to an in situ single pass intestinal perfusion assay to evaluate the influence of PPIs on fenofibrate absorption from LBFs in vivo. This coupled model allowed for real-time evaluation of the impact of supersaturation stabilization on absorptive drug flux and provided better discrimination between the different PPIs and formulations. In the presence of the in situ absorption sink, increased fenofibrate supersaturation resulted in increased drug exposure, and a good correlation was found between the degree of in vitro supersaturation and in vivo drug exposure. An improved in vitro-in vivo correlation was apparent when comparing the same formulation under different supersaturation conditions. These observations directly exemplify the potential utility of PPIs in promoting drug absorption from LBF, via stabilization of supersaturation, and further confirm that relatively brief periods of supersaturation may be sufficient to promote drug absorption, at least for highly permeable drugs such as fenofibrate.

Enhancing the incorporation of the patient's voice in drug development and evaluation.

PubMed

Chalasani, Meghana; Vaidya, Pujita; Mullin, Theresa

2018-01-01

People living with a condition are uniquely positioned to inform the understanding of the therapeutic context for drug development and evaluation. In 2012, the U.S. Food and Drug Administration (FDA) established the Patient-Focused Drug Development (PFDD) initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. PFDD meetings are unique among FDA public meetings, with a format designed to engage patients and elicit their perspectives on two topic areas: (1) the most significant symptoms of their condition and the impact of the condition on daily life; and, (2) their current approaches to treatment. FDA has conducted 24 disease-specific PFDD meetings to date. The lessons learned from PFDD meetings range from experiences common across rare diseases to more disease specific experiences that matter most to patients. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Patient-focused drug development is an ongoing effort and FDA looks forward to the next steps in advancing the science and the utilization of patient input throughout drug development and evaluation. The U.S. Food and Drug Administration (FDA) has multiple mechanisms for its regulators and staff to interact with patients -- but none quite like its novel Patient-Focused Drug Development (PFDD) initiative. FDA established the PFDD initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. Since the initiative's inception in 2012, FDA has held 24 PFDD meetings, covering a range of disease areas and hearing directly from thousands of patients and caregivers. FDA's PFDD meetings have also provided key stakeholders, including patient advocates, researchers, drug developers, healthcare providers, and other government officials, an opportunity to hear the patient's voice. The lessons learned include but are not limited to specific experiences that matter most to patients, patient perspectives on meaningful treatment benefits and how patients want to be engaged in the drug development process. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Further enhancing the incorporation of the patient's voice in drug development and evaluation continues to be a priority for FDA.

Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration.

PubMed

Davit, Barbara M; Nwakama, Patrick E; Buehler, Gary J; Conner, Dale P; Haidar, Sam H; Patel, Devvrat T; Yang, Yongsheng; Yu, Lawrence X; Woodcock, Janet

2009-10-01

In the US, manufacturers seeking approval to market a generic drug product must submit data demonstrating that the generic formulation provides the same rate and extent of absorption as (ie, is bioequivalent to) the innovator drug product. Thus, most orally administered generic drug products in the US are approved based on results of one or more clinical bioequivalence studies. To evaluate how well the bioequivalence measures of generic drugs approved in the US over a 12-year period compare with those of their corresponding innovator counterparts. This retrospective analysis compared the generic and innovator bioequivalence measures from 2070 single-dose clinical bioequivalence studies of orally administered generic drug products approved by the Food and Drug Administration (FDA) from 1996 to 2007 (12 y). Bioequivalence measures evaluated were drug peak plasma concentration (C(max)) and area under the plasma drug concentration versus time curve (AUC), representing drug rate and extent of absorption, respectively. The generic/innovator C(max) and AUC geometric mean ratios (GMRs) were determined from each of the bioequivalence studies, which used from 12 to 170 subjects. The GMRs from the 2070 studies were averaged. In addition, the distribution of differences between generic means and innovator means was determined for both C(max) and AUC. The mean +/- SD of the GMRs from the 2070 studies was 1.00 +/- 0.06 for C(max) and 1.00 +/- 0.04 for AUC. The average difference in C(max) and AUC between generic and innovator products was 4.35% and 3.56%, respectively. In addition, in nearly 98% of the bioequivalence studies conducted during this period, the generic product AUC differed from that of the innovator product by less than 10%. The criteria used to evaluate generic drug bioequivalence studies support the FDA's objective of approving generic drug formulations that are therapeutically equivalent to their innovator counterparts.

Rapidly disintegrating tablets containing taste masked metoclopramide hydrochloride prepared by extrusion-precipitation method.

PubMed

Randale, Shivsagar Ashok; Dabhi, Chandu Somatbhai; Tekade, Avinash Ramrao; Belgamwar, Veena Shailendra; Gattani, Surendra Ganeshlal; Surana, Sanjay Javarilal

2010-04-01

The purpose of this study was to mask the intensely bitter taste of metoclopramide HCl and to formulate a rapid disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing metoclopramide HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratio by the extrusion-precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.8, taste evaluation in oral cavity and molecular property. The complex having drug-polymer ratio of 1 : 2 shows significant taste masking, confirmed by drug release in SSF and in-vivo taste evaluation; therefore, it was selected for further study. Taste evaluation of DPCs in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) within 10 s, whereas, metoclopramide HCl was rated intensely bitter with a score of +3 for 10 s. Tablets were evaluated for various parameters like tensile strength, wetting time, water absorption ratio, in-vitro disintegration time, and disintegration in oral cavity. The effect of diluents, lubricants and sweetening agent (Xylisorb) on the disintegration time was also evaluated. Tablets of batch F3 containing mannitol and microcrystalline cellulose in the ratio 1 : 1 and 8% w/w crosspovidone showed faster disintegration (within 20 s) than the marketed formulation (180 s). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Tablets of batch F3 also revealed rapid drug release (t(90), 90 s) in SGF compared with marketed formulation (t(90), 600 s).

Cultural Competence for Evaluators: A Guide for Alcohol and Other Drug Abuse Prevention Practitioners Working with Ethnic/Racial Communities. OSAP Cultural Competence Series 1.

ERIC Educational Resources Information Center

Orlandi, Mario A., Ed.; And Others

As an introduction to a series on the array of issues in the implementation and evaluation of substance abuse prevention programs, this volume attempts to integrate two types of competence for alcohol and other drug abuse prevention program practitioners: program evaluation competence and cultural competence. The chapters in this document provide…

21 CFR 814.104 - Original applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... information to the Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and... Control Room, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd... or diagnose the disease or condition. The application also shall contain a discussion of the risks...

21 CFR 814.104 - Original applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... information to the Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and... Control Room, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd... or diagnose the disease or condition. The application also shall contain a discussion of the risks...

21 CFR 814.104 - Original applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... information to the Document Control Center (HFM-99), Center for Biologics Evaluation and Research, Food and... Control Room, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd... or diagnose the disease or condition. The application also shall contain a discussion of the risks...

Evaluation of emergency drug releases from the Centers for Disease Control and Prevention Quarantine Stations

PubMed Central

Roohi, Shahrokh; Grinnell, Margaret; Sandoval, Michelle; Cohen, Nicole J.; Crocker, Kimberly; Allen, Christopher; Dougherty, Cindy; Jolly, Julian; Pesik, Nicki

2018-01-01

The Centers for Disease Control and Prevention (CDC) Quarantine Stations distribute select lifesaving drug products that are not commercially available or are in limited supply in the United States for emergency treatment of certain health conditions. Following a retrospective analysis of shipment records, the authors estimated an average of 6.66 hours saved per shipment when drug products were distributed from quarantine stations compared to a hypothetical centralized site from CDC headquarters in Atlanta, GA. This evaluation supports the continued use of a decentralized model which leverages CDC's regional presence and maximizes efficiency in the distribution of lifesaving drugs. PMID:25779896

Evaluation of emergency drug releases from the Centers for Disease Control and Prevention Quarantine Stations.

PubMed

Roohi, Shahrokh; Grinnell, Margaret; Sandoval, Michelle; Cohen, Nicole J; Crocker, Kimberly; Allen, Christopher; Dougherty, Cindy; Jolly, Julian; Pesik, Nicki

2015-01-01

The Centers for Disease Control and Prevention (CDC) Quarantine Stations distribute select lifesaving drug products that are not commercially available or are in limited supply in the United States for emergency treatment of certain health conditions. Following a retrospective analysis of shipment records, the authors estimated an average of 6.66 hours saved per shipment when drug products were distributed from quarantine stations compared to a hypothetical centralized site from CDC headquarters in Atlanta, GA. This evaluation supports the continued use of a decentralized model which leverages CDC's regional presence and maximizes efficiency in the distribution of lifesaving drugs.

Evaluation of a new antinauseant drug for the prevention of motion sickness

NASA Technical Reports Server (NTRS)

Graybiel, A.; Knepton, J.

1977-01-01

The new drug, AHR 5645B, together with other drugs was evaluated in tests, conducted with eight male subjects, concerning its ability to prevent motion sickness. It was found that AHR 5645B, used in doses of 20, 50, and 100 mg, was not efficacious in preventing experimental motion sickness. A combination of 50 mg meclizine and 25 mg ephedrine sulfate produced the best results. Favorable results were also obtained with a combination of 12.5 mg promethazine hydrochloride and 12.5 mg ephedrine sulfate. The findings in the reported experiment point to the difficulty of identifying a highly efficacious antimotion sickness drug for everyone.

Preparation and evaluation of metoprolol tartrate sustained-release pellets using hot melt extrusion combined with hot melt coating.

PubMed

Yang, Yan; Shen, Lian; Li, Juan; Shan, Wei-Guang

2017-06-01

The objective of this study was to prepare and evaluate metoprolol tartrate sustained-release pellets. Cores were prepared by hot melt extrusion and coated pellets were prepared by hot melt coating. Cores were found to exist in a single-phase state and drug in amorphous form. Plasticizers had a significant effect on torque and drug content, while release modifiers and coating level significantly affected the drug-release behavior. The mechanisms of drug release from cores and coated pellets were Fickian diffusion and diffusion-erosion. The coated pellets exhibited sustained-release properties in vitro and in vivo.

Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite hydrogel beads for propranolol controlled release.

PubMed

Farhadnejad, Hassan; Mortazavi, Seyed Alireza; Erfan, Mohammad; Darbasizadeh, Behzad; Motasadizadeh, Hamidreza; Fatahi, Yousef

2018-05-01

The main aim of the present study was to design pH-sensitive nanocomposite hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)-propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite beads could potentially be used as oral drug delivery systems. PPN-as a model drug-was intercalated into the interlayer space of Mt clay mineral via the ion exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate nanocomposite hydrogel beads by association with carboxymethyl cellulose. The characterization of test samples was performed using different techniques: X-Ray Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and scanning electron microscopy (SEM). The drug encapsulation efficiency was evaluated by UV-vis spectroscopy, and was found to be high for Mt/CMC beads. In vitro drug release test was performed in the simulated gastrointestinal conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a controlled-release drug carrier. The drug release profiles indicated that the Mt-PPN/CMC nanocomposite beads had high stability against stomach acid and a sustained- and controlled-release profile for PPN under the simulated intestinal conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Multicentre study for validation of the French addictovigilance network reports assessment tool

PubMed Central

Hardouin, Jean Benoit; Rousselet, Morgane; Gerardin, Marie; Guerlais, Marylène; Guillou, Morgane; Bronnec, Marie; Sébille, Véronique; Jolliet, Pascale

2016-01-01

Aims The French health authority (ANSM) is responsible for monitoring medicinal and other drug dependencies. To support these activities, the ANSM manages a network of 13 drug dependence evaluation and information centres (Centres d'Evaluation et d'Information sur la Pharmacodépendance ‐ Addictovigilance ‐ CEIP‐A) throughout France. In 2006, the Nantes CEIP‐A created a new tool called the EGAP (Echelle de GrAvité de la Pharmacodépendance‐ drug dependence severity scale) based on DSM IV criteria. This tool allows the creation of a substance use profile that enables the drug dependence severity to be homogeneously quantified by assigning a score to each substance indicated in the reports from health professionals. This article describes the validation and psychometric properties of the drug dependence severity score obtained from the scale ( Clinicaltrials.gov NCT01052675). Method The validity of the EGAP construct, the concurrent validity and the discriminative ability of the EGAP score, the consistency of answers to EGAP items, the internal consistency and inter rater reliability of the EGAP score were assessed using statistical methods that are generally used for psychometric tests. Results The total EGAP score was a reliable and precise measure for evaluating drug dependence (Cronbach alpha = 0.84; ASI correlation = 0.70; global ICC = 0.92). In addition to its good psychometric properties, the EGAP is a simple and efficient tool that can be easily specified on the official ANSM notification form. Conclusion The good psychometric properties of the total EGAP score justify its use for evaluating the severity of drug dependence. PMID:27302554

Evaluation of naranjo adverse drug reactions probability scale in causality assessment of drug-induced liver injury.

PubMed

García-Cortés, M; Lucena, M I; Pachkoria, K; Borraz, Y; Hidalgo, R; Andrade, R J

2008-05-01

Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (kappa(w)) test. A total of 249 ratings were generated. Between-observer agreement was 45% with a kappa(w) value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, kappa(w): 0.71). Concordance between the two scales was 24% (kappa(w): 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity.

A systematic review of cost-effectiveness analyses of drugs for postmenopausal osteoporosis.

PubMed

Hiligsmann, Mickaël; Evers, Silvia M; Ben Sedrine, Wafa; Kanis, John A; Ramaekers, Bram; Reginster, Jean-Yves; Silverman, Stuart; Wyers, Caroline E; Boonen, Annelies

2015-03-01

Given the limited availability of healthcare resources and the recent introduction of new anti-osteoporosis drugs, the interest in the cost effectiveness of drugs in postmenopausal osteoporosis remains and even increases. This study aims to identify all recent economic evaluations on drugs for postmenopausal osteoporosis, to critically appraise the reporting quality, and to summarize the results. A literature search using Medline, the National Health Service Economic Evaluation database and the Cost-Effectiveness Analysis Registry was undertaken to identify original articles published between January 1, 2008 and December 31, 2013. Studies that assessed cost effectiveness of drugs in postmenopausal osteoporosis were included. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement was used to assess the quality of reporting of these articles. Of 1,794 articles identified, 39 studies fulfilled the inclusion criteria. They were conducted in 14 different countries and nine active interventions were assessed. When compared with no treatment, active osteoporotic drugs were generally cost effective in postmenopausal women aged over 60-65 years with low bone mass, especially those with prior vertebral fractures. Key drivers of cost effectiveness included individual fracture risk, medication adherence, selected comparators and country-specific analyses. Quality of reporting varied between studies with an average score of 17.9 out of 24 (range 7-21.5). This review found a substantial number of published cost-effectiveness analyses of drugs in osteoporosis in the last 6 years. Results and critical appraisal of these articles can help decision makers when prioritizing health interventions and can inform the development of future economic evaluations.

Drug interactions among commonly used medications. Chart simplifies data from critical literature review.

PubMed Central

Crowther, N. R.; Holbrook, A. M.; Kenwright, R.; Kenwright, M.

1997-01-01

OBJECTIVE: To simplify risk assessment, we have developed a way to present critically appraised drug interaction information through a chart. DATA SOURCES: Fifty drugs most frequently prescribed by Canadian family physicians and 16 drugs and substances that frequently interact with these drugs were the basis for a literature review. Drug interaction textbooks and MEDLINE (from 1966 to 1994) were searched for documented interactions. Reports of additive effects and animal or in vitro studies were excluded. STUDY SELECTION: All reports of interactions were evaluated for clinical effect, clinical significance, and quality of evidence. SYNTHESIS: Of the 464 drug-drug or drug-substance pairs evaluated, 387 (83.4%) demonstrated an interaction, 59 (12.7%) documented no effect, and 18 (3.9%) pairs had conflicting evidence. Five percent of interactions were of major clinical significance; only 1.3% were of major clinical significance and supported by good-quality evidence. By using symbols, colours, and legends in a "grid-map" format, a large amount of drug interaction information was reduced to a single-page chart suitable for a desk reference or wall mounting. CONCLUSIONS: Our chart organizes a large amount of drug interaction information in a format that allows for rapid appreciation of outcome, clinical significance, and quality of evidence. PMID:9386884

[Analysis of drug-related problems in a tertiary university hospital in Barcelona (Spain)].

PubMed

Ferrández, Olivia; Casañ, Borja; Grau, Santiago; Louro, Javier; Salas, Esther; Castells, Xavier; Sala, Maria

2018-05-07

To describe drug-related problems identified in hospitalized patients and to assess physicians' acceptance rate of pharmacists' recommendations. Retrospective observational study that included all drug-related problems detected in hospitalized patients during 2014-2015. Statistical analysis included a descriptive analysis of the data and a multivariate logistic regression to evaluate the association between pharmacists' recommendation acceptance rate and the variable of interest. During the study period 4587 drug-related problems were identified in 44,870 hospitalized patients. Main drug-related problems were prescription errors due to incorrect use of the computerized physician order entry (18.1%), inappropriate drug-drug combination (13.3%) and dose adjustment by renal and/or hepatic function (11.5%). Acceptance rate of pharmacist therapy advice in evaluable cases was 81.0%. Medical versus surgical admitting department, specific types of intervention (addition of a new drug, drug discontinuation and correction of a prescription error) and oral communication of the recommendation were associated with a higher acceptance rate. The results of this study allow areas to be identified on which to implement optimization strategies. These include training courses for physicians on the computerized physician order entry, on drugs that need dose adjustment with renal impairment, and on relevant drug interactions. Copyright © 2018 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

[Social support as a protective factor of recurrence after drug addiction treatment].

PubMed

Garmendia, María Luisa; Alvarado, María Elena; Montenegro, Mariano; Pino, Paulina

2008-02-01

Lack of social support can be one of the factors that influences recurrences of drug consumption after treatment of addictions. To assess the role of social support in maintaining drug abstinence after treatment. We studied 306 subjects that were treated in drug addiction centers, financed by the National Council for Drug Control (CONACE). At discharge, social and demographic data were recorded and the Medical Outcomes Study (MOS) questionnaire was given to evaluate social support. Subjects that achieved abstinence at the moment of discharge were contacted six months later and interrogated about eventual drug consumption thereafter. One hundred fifty three (76% male, aged 32+/-10 years) of 197 abstinent subjects at discharge, were located six months later. Of these, 108 (71%) were not consuming drugs. On univariate analysis, social support had a protective effect against recurrence of drug consumption (OR-0.98; CI 95%=0.96-0.99). This effect remained significant after adjusting for age, sex, occupational situation, mental health self-assessment, family history of alcohol and drug consumption, type of drug treatment and type of discharge as confounding variables (OR=0.97; CI 95%=0.94-0.99). These data provide evidence that social support protects against recurrence into drug consumption at least up to six months. Long-term effects should be evaluated.

Drug interactions between common illicit drugs and prescription therapies.

PubMed

Lindsey, Wesley T; Stewart, David; Childress, Darrell

2012-07-01

The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.

Evaluation of RxNorm for Medication Clinical Decision Support.

PubMed

Freimuth, Robert R; Wix, Kelly; Zhu, Qian; Siska, Mark; Chute, Christopher G

2014-01-01

We evaluated the potential use of RxNorm to provide standardized representations of generic drug name and route of administration to facilitate management of drug lists for clinical decision support (CDS) rules. We found a clear representation of generic drug name but not route of administration. We identified several issues related to data quality, including erroneous or missing defined relationships, and the use of different concept hierarchies to represent the same drug. More importantly, we found extensive semantic precoordination of orthogonal concepts related to route and dose form, which would complicate the use of RxNorm for drug-based CDS. This study demonstrated that while RxNorm is a valuable resource for the standardization of medications used in clinical practice, additional work is required to enhance the terminology so that it can support expanded use cases, such as managing drug lists for CDS.

Evaluation of RxNorm for Medication Clinical Decision Support

PubMed Central

Freimuth, Robert R.; Wix, Kelly; Zhu, Qian; Siska, Mark; Chute, Christopher G.

2014-01-01

We evaluated the potential use of RxNorm to provide standardized representations of generic drug name and route of administration to facilitate management of drug lists for clinical decision support (CDS) rules. We found a clear representation of generic drug name but not route of administration. We identified several issues related to data quality, including erroneous or missing defined relationships, and the use of different concept hierarchies to represent the same drug. More importantly, we found extensive semantic precoordination of orthogonal concepts related to route and dose form, which would complicate the use of RxNorm for drug-based CDS. This study demonstrated that while RxNorm is a valuable resource for the standardization of medications used in clinical practice, additional work is required to enhance the terminology so that it can support expanded use cases, such as managing drug lists for CDS. PMID:25954360

Dual drug release from hydrogels covalently containing polymeric micelles that possess different drug release properties.

PubMed

Murata, Mari; Uchida, Yusuke; Takami, Taku; Ito, Tomoki; Anzai, Ryosuke; Sonotaki, Seiichi; Murakami, Yoshihiko

2017-05-01

In the present study, we designed hydrogels for dual drug release: the hydrogels that covalently contained the polymeric micelles that possess different drug release properties. The hydrogels that were formed from polymeric micelles possessing a tightly packed (i.e., well-entangled) inner core exhibited a higher storage modulus than the hydrogels that were formed from the polymeric micelles possessing a loosely packed structure. Furthermore, we conducted release experiments and fluorescent observations to evaluate the profiles depicting the release of two compounds, rhodamine B and auramine O, from either polymeric micelles or hydrogels. According to our results, (1) hydrogels that covalently contains polymeric micelles that possess different drug release properties successfully exhibit the independent release behaviors of the two compounds and (2) fluorescence microscopy can greatly facilitate efforts to evaluate drug release properties of materials. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative structure-property relationship (QSPR) modeling of drug-loaded polymeric micelles via genetic function approximation.

PubMed

Wu, Wensheng; Zhang, Canyang; Lin, Wenjing; Chen, Quan; Guo, Xindong; Qian, Yu; Zhang, Lijuan

2015-01-01

Self-assembled nano-micelles of amphiphilic polymers represent a novel anticancer drug delivery system. However, their full clinical utilization remains challenging because the quantitative structure-property relationship (QSPR) between the polymer structure and the efficacy of micelles as a drug carrier is poorly understood. Here, we developed a series of QSPR models to account for the drug loading capacity of polymeric micelles using the genetic function approximation (GFA) algorithm. These models were further evaluated by internal and external validation and a Y-randomization test in terms of stability and generalization, yielding an optimization model that is applicable to an expanded materials regime. As confirmed by experimental data, the relationship between microstructure and drug loading capacity can be well-simulated, suggesting that our models are readily applicable to the quantitative evaluation of the drug-loading capacity of polymeric micelles. Our work may offer a pathway to the design of formulation experiments.

Quantitative Structure-Property Relationship (QSPR) Modeling of Drug-Loaded Polymeric Micelles via Genetic Function Approximation

PubMed Central

Lin, Wenjing; Chen, Quan; Guo, Xindong; Qian, Yu; Zhang, Lijuan

2015-01-01

Self-assembled nano-micelles of amphiphilic polymers represent a novel anticancer drug delivery system. However, their full clinical utilization remains challenging because the quantitative structure-property relationship (QSPR) between the polymer structure and the efficacy of micelles as a drug carrier is poorly understood. Here, we developed a series of QSPR models to account for the drug loading capacity of polymeric micelles using the genetic function approximation (GFA) algorithm. These models were further evaluated by internal and external validation and a Y-randomization test in terms of stability and generalization, yielding an optimization model that is applicable to an expanded materials regime. As confirmed by experimental data, the relationship between microstructure and drug loading capacity can be well-simulated, suggesting that our models are readily applicable to the quantitative evaluation of the drug-loading capacity of polymeric micelles. Our work may offer a pathway to the design of formulation experiments. PMID:25780923

Development of a replicated database of DHCP data for evaluation of drug use.

PubMed Central

Graber, S E; Seneker, J A; Stahl, A A; Franklin, K O; Neel, T E; Miller, R A

1996-01-01

This case report describes development and testing of a method to extract clinical information stored in the Veterans Affairs (VA) Decentralized Hospital Computer System (DHCP) for the purpose of analyzing data about groups of patients. The authors used a microcomputer-based, structured query language (SQL)-compatible, relational database system to replicate a subset of the Nashville VA Hospital's DHCP patient database. This replicated database contained the complete current Nashville DHCP prescription, provider, patient, and drug data sets, and a subset of the laboratory data. A pilot project employed this replicated database to answer questions that might arise in drug-use evaluation, such as identification of cases of polypharmacy, suboptimal drug regimens, and inadequate laboratory monitoring of drug therapy. These database queries included as candidates for review all prescriptions for all outpatients. The queries demonstrated that specific drug-use events could be identified for any time interval represented in the replicated database. PMID:8653451

Development of a replicated database of DHCP data for evaluation of drug use.

PubMed

Graber, S E; Seneker, J A; Stahl, A A; Franklin, K O; Neel, T E; Miller, R A

1996-01-01

This case report describes development and testing of a method to extract clinical information stored in the Veterans Affairs (VA) Decentralized Hospital Computer System (DHCP) for the purpose of analyzing data about groups of patients. The authors used a microcomputer-based, structured query language (SQL)-compatible, relational database system to replicate a subset of the Nashville VA Hospital's DHCP patient database. This replicated database contained the complete current Nashville DHCP prescription, provider, patient, and drug data sets, and a subset of the laboratory data. A pilot project employed this replicated database to answer questions that might arise in drug-use evaluation, such as identification of cases of polypharmacy, suboptimal drug regimens, and inadequate laboratory monitoring of drug therapy. These database queries included as candidates for review all prescriptions for all outpatients. The queries demonstrated that specific drug-use events could be identified for any time interval represented in the replicated database.

In vivo evaluation of drug delivery after ultrasound application: A new use for the photoacoustic technique

NASA Astrophysics Data System (ADS)

Barja, P. R.; Acosta-Avalos, D.; Rompe, P. C. B.; Dos Anjos, F. H.; Marciano, F. R.; da Silva, M. D.

2005-06-01

Ultrasound application is a therapeutical resource widely employed in physiotherapy. One of its applications is the phonophoresis, a technique in which the ultrasound radiation is utilized to deliver drugs through the skin to soft tissues. The proposal of our study was to employ the Photoacoustic Technique to evaluate the efficacy of such treatment, analyzing if phonophoresis could enhance drug delivery through skin when compared to the more traditional method of manual massage. The configuration of the system employed was such that it was possible to perform in vivo measurements, which is a pre-requisite for this kind of study. The changes observed in the photoacoustic signal amplitude after each form of drug application were attributed to changes in the thermal effusivity of the system, due to penetration of the drug. The technique was able to detect differences in drug delivery between the specified physiotherapy treatments, indicating that phonophoresis enhances drug absorption by tissue.

AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress.

PubMed

Liu, Yu; Fares, Matthew; Dunham, Noah P; Gao, Zi; Miao, Kun; Jiang, Xueyuan; Bollinger, Samuel S; Boal, Amie K; Zhang, Xin

2017-07-17

Drug-induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety of drugs is regularly evaluated using cytotoxicity assays that measure cell death. However, these assays provide limited insights into the presence of proteome stress in live cells. A fluorogenic protein sensor is reported to detect drug-induced proteome stress prior to cell death. An aggregation prone Halo-tag mutant (AgHalo) was evolved to sense proteome stress through its aggregation. Detection of such conformational changes was enabled by a fluorogenic ligand that fluoresces upon AgHalo forming soluble aggregates. Using 5 common anticancer drugs, we exemplified detection of differential proteome stress before any cell death was observed. Thus, this sensor can be used to evaluate drug safety in a regime that the current cytotoxicity assays cannot cover and be generally applied to detect proteome stress induced by other toxins. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determine equilibrium dissociation constant of drug-membrane receptor affinity using the cell membrane chromatography relative standard method.

PubMed

Ma, Weina; Yang, Liu; Lv, Yanni; Fu, Jia; Zhang, Yanmin; He, Langchong

2017-06-23

The equilibrium dissociation constant (K D ) of drug-membrane receptor affinity is the basic parameter that reflects the strength of interaction. The cell membrane chromatography (CMC) method is an effective technique to study the characteristics of drug-membrane receptor affinity. In this study, the K D value of CMC relative standard method for the determination of drug-membrane receptor affinity was established to analyze the relative K D values of drugs binding to the membrane receptors (Epidermal growth factor receptor and angiotensin II receptor). The K D values obtained by the CMC relative standard method had a strong correlation with those obtained by the frontal analysis method. Additionally, the K D values obtained by CMC relative standard method correlated with pharmacological activity of the drug being evaluated. The CMC relative standard method is a convenient and effective method to evaluate drug-membrane receptor affinity. Copyright © 2017 Elsevier B.V. All rights reserved.

[Risks of drug-nutrient interaction for the elderly in long-term care institutions].

PubMed

Peixoto, Jessica Sereno; Salci, Maria Aparecida; Radovanovic, Cremilde Aparecida Trindade; Salci, Tania Pereira; Torres, Maricy Morbin; Carreira, Lígia

2012-09-01

This study was aimed at verifying the risks of drug-nutrient interactions in the elderly residents of a long-term care institution. Descriptive study of quantitative approach, performed in 73 elderly people. Data collection occurred in 2008 through analysis of medical records, diet history and evaluation of the BMI. Data evidenced that the drugs more frequently used were the ones for nervous and cardiovascular systems, totaling approximately 66% of the prescriptions; among the 375 drugs prescribed 166 make some type of interaction, 32.0% reduce the effect of drug absorption when there is use with caffeine and 14.3% reduce the B12 vitamin absorption. Taking several drugs of continuous use may cause damage to the absorption of nutrients. The action of the health team becomes vital, through careful evaluation of the administered drugs, diet and interaction between them, to benefit the elderly with a better use of the therapeutics and improvement of the nutritional conditions.

New decision-making processes for the pricing of health technologies in Japan: The FY 2016/2017 pilot phase for the introduction of economic evaluations.

PubMed

Shiroiwa, Takeru; Fukuda, Takashi; Ikeda, Shunya; Takura, Tomoyuki

2017-08-01

Economic evaluation is used for decision-making processes in healthcare technologies in many developed countries. In Japan, no health economic data have been requested for drugs, medical devices, and interventions till date. However, economic evaluation is gradually gaining importance, and a trial implementation of the cost-effectiveness evaluation of drugs and medical devices has begun. Discussions on economic evaluation began in May 2012 within a newly established sub-committee of the Chuikyo, referred to as the "Special Committee on Cost Effectiveness." After four years of discussions, this committee determined that during the trial implementation, the results of the cost-effectiveness evaluation would be used for the re-pricing of drugs and medical devices at the end of fiscal year (FY) 2017. Chuikyo selected 13 products (7 drugs and 6 medical devices) as targets for this evaluation. These products will be evaluated until the end of FY 2017 based on the following process: manufacturers will submit the data of economic evaluation; the National Institute of Public Health will coordinate the review process; academic groups will perform the actual review of the submitted data, and the expert committee will appraise these data. This represents the first step to introducing cost-effectiveness analysis in the Japanese healthcare system. We believe that these efforts will contribute to the efficiency and sustainability of the Japanese healthcare system. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

21 CFR 207.7 - Establishment registration and product listing for human blood and blood products and for medical...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Establishment registration and product listing for human blood and blood products and for medical devices. 207.7 Section 207.7 Food and Drugs FOOD AND DRUG... Repository Team (HFD-143), Center for Drug Evaluation and Research, FDA, and list their drug products in...

21 CFR 207.7 - Establishment registration and product listing for human blood and blood products and for medical...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Establishment registration and product listing for human blood and blood products and for medical devices. 207.7 Section 207.7 Food and Drugs FOOD AND DRUG... Repository Team (HFD-143), Center for Drug Evaluation and Research, FDA, and list their drug products in...

Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study.

PubMed

Kesselheim, Aaron S; Wang, Bo; Franklin, Jessica M; Darrow, Jonathan J

2015-09-23

To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Cohort study. FDA approved novel therapeutics between 1987 and 2014. Publicly available sources provided each drug's year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA's four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review. Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not. The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P<0.001), and a 2.4% increase in the proportion of drugs associated with at least one such program (odds ratio 1.024, 95% confidence interval 1.006 to 1.043, P=0.009). Driving this trend was an increase in the proportion of approved, non-first in class drugs associated with at least one program for drugs (P=0.03 for interaction). In the past two decades, drugs newly approved by the FDA have been associated with an increasing number of expedited development or review programs. Though expedited programs should be strictly limited to drugs providing noticeable clinical advances, this trend is being driven by drugs that are not first in class and thus potentially less innovative. © Kesselheim et al 2015.

77 FR 52741 - Compliance Policy Guide Sec. 420.300 Changes in Compendial Specifications and New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993, 301... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0135... Supplements; Withdrawal of Guidance AGENCY: Food and Drug Administration, HHS. ACTION: Notice; withdrawal...

75 FR 68802 - Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-09

.... This notice is the Agency's report on the status of the studies and clinical trials that applicants... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm... and Research (HFM- 25), Food and Drug Administration, 1400 Rockville Pike, Rockville, MD 20852, 301...

Matching Judicial Supervision to Clients' Risk Status in Drug Court

ERIC Educational Resources Information Center

Marlowe, Douglas B.; Festinger, David S.; Lee, Patricia A.; Dugosh, Karen L.; Benasutti, Kathleen M.

2006-01-01

This article reports outcomes from a program of experimental research evaluating the risk principle in drug courts. Prior studies revealed that participants who were high risk and had (a) antisocial personality disorder or (b) a prior history of drug abuse treatment performed better in drug court when scheduled to attend biweekly judicial status…

77 FR 20025 - Draft Guidance for Industry on Compliance Policy for Reporting Drug Sample Distribution...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-03

... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD... Evaluation and Research (CBER), Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 4288, Silver Spring, MD...

Condoning Drug Education Programs at Colleges and Universities.

ERIC Educational Resources Information Center

Kaczynski, Daniel J.

This report presents the evaluation results gathered from a 2-year study of a drug prevention program involving a consortia of nine colleges and universities located in Alabama and Florida. The consortia effort was intended to: (1) strengthen their respective drug prevention activities; (2) develop policies governing alcohol and drugs; (3)…

21 CFR 601.4 - Issuance and denial of license.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Director, Center for Drug Evaluation and Research that the establishment(s) and the product meet the... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Issuance and denial of license. 601.4 Section 601.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

78 FR 66745 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD...], Center for Drug Evaluation and Research (HFD-600), Food and Drug Administration, 7520 Standish Pl... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369...

78 FR 37230 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-20

... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD...], Center for Drug Evaluation and Research (HFD-600), Food and Drug Administration, 7519 Standish Pl... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369...

75 FR 45646 - Design of Clinical Trials of Aerosolized Antimicrobials for the Treatment of Cystic Fibrosis...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... Drug Evaluation and Research,Food and Drug Administration, Office of Antimicrobial Products, 10903 New... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001... Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. SUMMARY: The Food...

76 FR 14025 - Guidance for Industry on Planning for the Effects of High Absenteeism To Ensure Availability of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... Necessary Drug Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY... Evaluation and Research's (CDER's) intended approach to assist in avoiding drug product shortages that may... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0568...

21 CFR 607.25 - Information required for establishment registration and blood product listing.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Information required for establishment registration and blood product listing. 607.25 Section 607.25 Food and Drugs FOOD AND DRUG ADMINISTRATION... the manufacturer issued by the Center for Biologics Evaluation and Research, Food and Drug...

21 CFR 601.4 - Issuance and denial of license.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Director, Center for Drug Evaluation and Research that the establishment(s) and the product meet the... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Issuance and denial of license. 601.4 Section 601.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 607.25 - Information required for establishment registration and blood product listing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Information required for establishment registration and blood product listing. 607.25 Section 607.25 Food and Drugs FOOD AND DRUG ADMINISTRATION... the manufacturer issued by the Center for Biologics Evaluation and Research, Food and Drug...

77 FR 74669 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD...], Center for Drug Evaluation and Research (HFD-600), Food and Drug Administration, 7519 Standish Pl... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369...

Biophase equilibration times.

PubMed

Veng-Pedersen, P; Mandema, J W; Danhof, M

1991-09-01

Various methods for describing how quickly a drug equilibrates at the biophase are proposed. The biophase equilibration time (BET) is the time it takes the biophase drug level to reach a given percentage (p) of its predicted steady state in a drug administration that leads to a steady-state condition. The time to reach biophase equilibrium may be defined as the BET value for p = 95, and the 50% biophase equilibration time is obtained when p = 50. Biophase equilibration profiles (BEPs), obtained by plotting p versus BET, give a dynamic representation of the approach to equilibrium and may serve as an indicator of the rate of drug delivery to the biophase. A pharmacodynamic system analysis method is proposed to determine BETs and BEPs from the biophase conduction function. The approach is demonstrated using pharmacodynamic data from the CNS effect of amobarbital evaluated by an aperiodic analysis of EEG recordings. The relevance of the BET and/or BEP principles in optimal computer-controlled drug infusion, drug design, and evaluation of targeted drug delivery is discussed. Both vascular and extravascular drug administrations are considered in the analysis.

Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations.

PubMed

Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

2014-03-14

This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

21 CFR 312.48 - Dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Dispute resolution. 312.48 Section 312.48 Food and... division in FDA's Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research... 20. (c) Scientific and medical disputes. (1) When scientific or medical disputes arise during the...

The "Anatomy" of a Performance-Enhancing Drug Test in Sports

ERIC Educational Resources Information Center

Werner, T. C.

2012-01-01

The components of a performance-enhancing drug (PED) test in sports include sample selection, collection, establishing sample integrity, sample pretreatment, analyte detection, data evaluation, reporting results, and action taken based on the result. Undergraduate curricula generally focus on the detection and evaluation steps of an analytical…

21 CFR 601.92 - Withdrawal procedures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... opportunity for a hearing. The Director of the Center for Biologics Evaluation and Research or the Director of the Center for Drug Evaluation and Research will give the applicant notice of an opportunity for a... issues involved and to provide advice and recommendations to the Commissioner of Food and Drugs. (2) The...

21 CFR 601.92 - Withdrawal procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... opportunity for a hearing. The Director of the Center for Biologics Evaluation and Research or the Director of the Center for Drug Evaluation and Research will give the applicant notice of an opportunity for a... issues involved and to provide advice and recommendations to the Commissioner of Food and Drugs. (2) The...

Evaluating the reliability and accuracy of the promotional brochures for the generic pharmaceutical companies in Iraq using World Health Organization guidelines

PubMed Central

Mikhael, Ehab Mudher

2015-01-01

Background: Pharmaceutical industries worldwide are heavily involved in aggressive drug promotions. Physician targeted promotion through medical representatives is one of the most common tactic for drug promotion by pharmaceutical drug companies. WHO states that medical representatives to work in an ethical way should make available to prescribers and dispensers complete and unbiased information for each product discussed; therefore this study aimed to evaluate the ethics in the medical brochures of generic pharmaceutical companies that are given through medical representatives to physicians in Iraq. Materials and Methods: An observational, cross-sectional study was conducted in Iraq – Baghdad from February to April 2014. Promotional drug brochures were collected mainly from pharmaceutical exhibition during attendance of medical conferences that were sponsored by generic pharmaceutical companies. Evaluation of each brochure was based primarily on WHO criteria for ethical medicinal drug promotion. The availability of emotional pictures in each brochure was also examined. Furthermore, references were checked to find their retrievability, source, and authenticity of presentations. Results: Most medical brochures were for antibiotics, and drugs for cardiovascular diseases. All brochures mention drug name, with its active ingredient and indication, but there is a significant absence for drug interaction, while drug side effects and contraindications if present were written in a small font. Emotional picture presented in 70% of brochures. Reference citation was present in 72% of brochures, however only 75% of references in these brochures were correct. Conclusions: The information that is provided in medical brochures is biased and mainly persuasive since it is mainly focusing on the positive aspect of drug therapy. PMID:25709340

Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels.

PubMed

Wang, Bo; Canestaro, William J; Choudhry, Niteesh K

2014-12-01

Genetic biomarkers that predict a drug's efficacy or likelihood of toxicity are assuming increasingly important roles in the personalization of pharmacotherapy, but concern exists that evidence that links use of some biomarkers to clinical benefit is insufficient. Nevertheless, information about the use of biomarkers appears in the labels of many prescription drugs, which may add confusion to the clinical decision-making process. To evaluate the evidence that supports pharmacogenomic biomarker testing in drug labels and how frequently testing is recommended. Publicly available US Food and Drug Administration databases. We identified drug labels that described the use of a biomarker and evaluated whether the label contained or referenced convincing evidence of its clinical validity (ie, the ability to predict phenotype) and clinical utility (ie, the ability to improve clinical outcomes) using guidelines published by the Evaluation of Genomic Applications in Practice and Prevention Working Group. We graded the completeness of the citation of supporting studies and determined whether the label recommended incorporation of biomarker test results in therapeutic decision making. Of the 119 drug-biomarker combinations, only 43 (36.1%) had labels that provided convincing clinical validity evidence, whereas 18 (15.1%) provided convincing evidence of clinical utility. Sixty-one labels (51.3%) made recommendations about how clinical decisions should be based on the results of a biomarker test; 36 (30.3%) of these contained convincing clinical utility data. A full description of supporting studies was included in 13 labels (10.9%). Fewer than one-sixth of drug labels contained or referenced convincing evidence of clinical utility of biomarker testing, whereas more than half made recommendations based on biomarker test results. It may be premature to include biomarker testing recommendations in drug labels when convincing data that link testing to patient outcomes do not exist.

Confocal fluorescence microscopy: An ultra-sensitive tool used to evaluate intracellular antiretroviral nano-drug delivery in HeLa cells

NASA Astrophysics Data System (ADS)

Mandal, Subhra; Zhou, You; Shibata, Annemarie; Destache, Christopher J.

2015-08-01

In the last decade, confocal fluorescence microscopy has emerged as an ultra-sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular-level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the world's major health threats by claiming approximately 7,000 new infections daily worldwide. Although combination antiretroviral drugs (cARV) therapy has improved the life-expectancy of HIV-infected patients, routine use of high doses of cARV has serious health consequences and requires complete adherence to the regimen for success. Thus, our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co-glycolic acid) (PLGA) nanoparticles (cARV-NPs) as drug delivery system. However, important aspects of cARV-NPs that require special emphasis are their cellular-uptake, potency, and sustained drug release efficiency over-time. In this article, ultra-sensitive confocal microscopy is been used to evaluate the uptake and sustained drug release kinetics of cARV-NPs in HeLa cells. To evaluate with the above goal, instead of cARV-drug, Rhodamine6G dye (fluorescent dye) loaded NPs (Rho6G NPs) have been formulated. To correlate the Rhodamin6G release kinetics with the ARV release from NPs, a parallel HPLC study was also performed. The results obtained indicate that Rho6G NPs were efficiently taken up at low concentration (<500 ng/ml) and that release was sustained for a minimum of 4 days of treatment. Therefore, high drug assimilation and sustained release properties of PLGA-NPs make them an attractive vehicle for cARV nano-drug delivery with the potential to reduce drug dosage as well as the number of drug administrations per month.

Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation.

PubMed

Ha, Michael A; Sieg, Adam C

2017-02-01

Extracorporeal membrane oxygenation (ECMO) is a life-support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965-July 2016), EMBASE (1965-July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward. © 2016 Pharmacotherapy Publications, Inc.

Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants

PubMed Central

Zhu, Qinchang; Yu, Zhiqiang; Kabashima, Tsutomu; Yin, Sheng; Dragusha, Shpend; El-Mahdy, Ahmed F. M.; Ejupi, Valon; Shibata, Takayuki; Kai, Masaaki

2015-01-01

Convenient drug-resistance testing of viral mutants is indispensable to effective treatment of viral infection. We developed a novel fluorometric assay for phenotypic differentiation of drug-resistant mutants of human immunodeficiency virus-I protease (HIV-PR) which uses enzymatic and peptide-specific fluorescence (FL) reactions and high-performance liquid chromatography (HPLC) of three HIV-PR substrates. This assay protocol enables use of non-purified enzyme sources and multiple substrates for the enzymatic reaction. In this study, susceptibility of HIV mutations to drugs was evaluated by selective formation of three FL products after the enzymatic HIV-PR reaction. This proof-of-concept study indicates that the present HPLC-FL method could be an alternative to current phenotypic assays for the evaluation of HIV drug resistance. PMID:25988960

In vitro-ex vivo correlations between a cell-laden hydrogel and mucosal tissue for screening composite delivery systems

PubMed Central

Blakney, Anna K.; Little, Adam B.; Jiang, Yonghou; Woodrow, Kim A.

2017-01-01

Composite delivery systems where drugs are electrospun in different layers and vary the drug stacking-order are posited to affect bioavailability. We evaluated how the formulation characteristics of both burst- and sustained-release electrospun fibers containing three physicochemically diverse drugs: dapivirine (DPV), maraviroc (MVC) and tenofovir (TFV) affect in vitro and ex vivo release. We developed a poly(hydroxyethyl methacrylate) (pHEMA) hydrogel release platform for the rapid, inexpensive in vitro evaluation of burst- and sustained-release topical or dermal drug delivery systems with varying microarchitecture. We investigated properties of the hydrogel that could recapitulate ex vivo release into nonhuman primate vaginal tissue. Using a DMSO extraction protocol and HPLC analysis, we achieved >93% recovery from the hydrogels and >88% recovery from tissue explants for all three drugs. We found that DPV loading, but not stacking order (layers of fiber containing a single drug) or microarchitecture (layers with isolated drug compared to all drugs in the same layer) impacted the burst release in vitro and ex vivo. Our burst-release formulations showed a correlation for DPV accumulation between the hydrogel and tissue (R2=0.80), but the correlation was not significant for MVC or TFV. For the sustained release formulations, the PLGA/PCL content did not affect TFV release in vitro or ex vivo. Incorporation of cells into the hydrogel matrix improved the correlation between hydrogel and tissue explant release for TFV. We expect that this hydrogel tissue mimic maybe a promising preclinical model to evaluate topical or transdermal drug delivery systems with complex microarchitectures. PMID:28222612

Predicting transporter-mediated drug interactions: Commentary on: "Pharmacokinetic evaluation of a drug transporter cocktail consisting of digoxin, furosemide, metformin and rosuvastatin" and "Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A".

PubMed

Zhang, L; Sparreboom, A

2017-04-01

Transporters, expressed in various tissues, govern the absorption, distribution, metabolism, and excretion of drugs, and consequently their inherent safety and efficacy profiles. Drugs may interact with a transporter as a substrate and/or an inhibitor. Understanding transporter-mediated drug-drug interactions (DDIs), in addition to enzyme-mediated DDIs, is an integral part of risk assessment in drug development and regulatory review because the concomitant use of more than one medication in patients is common. © 2016 ASCPT.

Using Respondent-Driven Sampling to Recruit Illegal Drug Purchasers to Evaluate a Drug Market Intervention.

PubMed

Ober, Allison J; Sussell, Jesse; Kilmer, Beau; Saunders, Jessica; Heckathorn, Douglas D

2016-04-01

Violent drug markets are not as prominent as they once were in the United States, but they still exist and are associated with significant crime and lower quality of life. The drug market intervention (DMI) is an innovative strategy that uses focused deterrence, community engagement, and incapacitation to reduce crime and disorder associated with these markets. Although studies show that DMI can reduce crime and overt drug activity, one perspective is prominently missing from these evaluations: those who purchase drugs. This study explores the use of respondent-driven sampling (RDS)-a statistical sampling method-to approximate a representative sample of drug users who purchased drugs in a targeted DMI market to gain insight into the effect of a DMI on market dynamics. Using RDS, we recruited individuals who reported hard drug use (crack or powder cocaine, heroin, methamphetamine, or illicit use of prescriptions opioids) in the last month to participate in a survey. The main survey asked about drug use, drug purchasing, and drug market activity before and after DMI; a secondary survey asked about network characteristics and recruitment. Our sample of 212 respondents met key RDS assumptions, suggesting that the characteristics of our weighted sample approximate the characteristics of the drug user network. The weighted estimates for market purchasers are generally valid for inferences about the aggregate population of customers, but a larger sample size is needed to make stronger inferences about the effects of a DMI on drug market activity. © The Author(s) 2016.

Identification of Drug Characteristics for Implementing Multiregional Clinical Trials Including Japan.

PubMed

Rokuda, Mitsuhiro; Matsumaru, Naoki; Tsukamoto, Katsura

2018-02-01

Multiregional clinical trials (MRCT) are a standard strategy used to improve global drug approval efficiency and the feasibility of clinical trials. Japan is the world's third largest drug market with a unique health care system, making it a key inclusion as an operational region for MRCT (MRCT-JP) for global drug development. We aimed to identify the factors required for efficient drug development by comprehensively reviewing the clinical trials of drugs approved in Japan to identify the factors associated with whether or not MRCT-JP is implemented. We surveyed the review reports and summaries of application data published by the Pharmaceuticals and Medical Devices Agency. We identified drugs for which the clinical trial data package included MRCT-JP and selected the same number of drugs for which the clinical trial data package did not include MRCT-JP from the most recent survey period for comparison. We also examined other publication information, in addition to the review reports, as necessary. The influence of each explanatory variable was analyzed by logistic regression analysis, with whether or not MRCT-JP was implemented as the explanatory variable. Statistical significance was set at 5%. In the survey period up to September 2017, 165 drugs developed with MRCT-JP were approved for manufacture and sale in Japan. "Respiratory system," "inhalation," "biological drug," and "under review" evaluation status for the United States, European Union, and other areas, "approved" evaluation status for the United States, "new ingredients," "priority review," "non-Japanese firm," and "Top 1-10" and "Top 11-20" drug sales rankings for pharmaceutical companies were identified as potential factors leading to the implementation of MRCT-JP. In contrast, "general anti-infectives for systemic use," "various," "external," "chemical compound," "unsubmitted" evaluation status for both the United States and European Union, and "Top 51+" drug sales rankings were potential factors for not implementing MRCT-JP. Therapeutic classification and agent type, in addition to capital type and United States and European Union evaluation status suggested by a previous study, were associated with implementing MRCT-JP. It is important to determine the best way to utilize MRCT-JP to maximize the value of products. Our findings were based on successful cases and may therefore be helpful for designing clinical development plans. Appropriate use of MRCT-JP will improve productivity in the pharmaceutical industry. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

Definition of variables required for comprehensive description of drug dosage and clinical pharmacokinetics.

PubMed

Medem, Anna V; Seidling, Hanna M; Eichler, Hans-Georg; Kaltschmidt, Jens; Metzner, Michael; Hubert, Carina M; Czock, David; Haefeli, Walter E

2017-05-01

Electronic clinical decision support systems (CDSS) require drug information that can be processed by computers. The goal of this project was to determine and evaluate a compilation of variables that comprehensively capture the information contained in the summary of product characteristic (SmPC) and unequivocally describe the drug, its dosage options, and clinical pharmacokinetics. An expert panel defined and structured a set of variables and drafted a guideline to extract and enter information on dosage and clinical pharmacokinetics from textual SmPCs as published by the European Medicines Agency (EMA). The set of variables was iteratively revised and evaluated by data extraction and variable allocation of roughly 7% of all centrally approved drugs. The information contained in the SmPC was allocated to three information clusters consisting of 260 variables. The cluster "drug characterization" specifies the nature of the drug. The cluster "dosage" provides information on approved drug dosages and defines corresponding specific conditions. The cluster "clinical pharmacokinetics" includes pharmacokinetic parameters of relevance for dosing in clinical practice. A first evaluation demonstrated that, despite the complexity of the current free text SmPCs, dosage and pharmacokinetic information can be reliably extracted from the SmPCs and comprehensively described by a limited set of variables. By proposing a compilation of variables well describing drug dosage and clinical pharmacokinetics, the project represents a step forward towards the development of a comprehensive database system serving as information source for sophisticated CDSS.

Drug utilization research in primary health care as exemplified by physicians' quality assessment groups.

PubMed

von Ferber, L; Luciano, A; Köster, I; Krappweis, J

1992-11-01

Drugs in primary health care are often prescribed for nonrational reasons. Drug utilization research investigates the prescription of drugs with an eye to medical, social and economic causes and consequences of the prescribed drug's utilization. The results of this research show distinct differences in drug utilization in different age groups and between men and women. Indication and dosage appear irrational from a textbook point of view. This indicates nonpharmacological causes of drug utilization. To advice successfully changes for the better quality assessment groups of primary health care physicians get information about their established behavior by analysis of their prescriptions. The discussion and the comparisons in the group allow them to recognize their irrational prescribing and the social, psychological and economic reasons behind it. Guidelines for treatment are worked out which take into account the primary health care physician's situation. After a year with 6 meetings of the quality assessment groups the education process is evaluated by another drug utilization analysis on the basis of the physicians prescription. The evaluation shows a remarkable improvement of quality and cost effectiveness of the drug therapy of the participating physicians.

An investigation into the characteristics and drug release properties of multiple W/O/W emulsion systems containing low concentration of lipophilic polymeric emulsifier.

PubMed

Vasiljevic, Dragana; Parojcic, Jelena; Primorac, Marija; Vuleta, Gordana

2006-02-17

Multiple W/O/W emulsions with high content of inner phase (Phi1=Phi2=0.8) were prepared using relatively low concentrations of lipophilic polymeric primary emulsifier, PEG 30-dipolyhydroxystearate, and diclofenac diethylamine (DDA) as a model drug. The investigated formulations were characterized and their stability over the time was evaluated by dynamic and oscillatory rheological measurements, microscopic analysis and in vitro drug release study. In vitro release profiles of the selected model drug were evaluated in terms of the effective diffusion coefficients and flux of the released drug. The multiple emulsion samples exhibited good stability during the ageing time. Concentration of the lipophilic primary emulsifier markedly affected rheological behaviour as well as the droplet size and in vitro drug release kinetics of the investigated systems. The multiple emulsion systems with highest concentration (2.4%, w/w) of the primary emulsifier had the lowest droplet size and the highest apparent viscosity and highest elastic characteristics. Drug release data indicated predominately diffusional drug release mechanism with sustained and prolonged drug release accomplished with 2.4% (w/w) of lipophilic emulsifier employed.

A toxicity assessment of 30 pharmaceuticals using Aliivibrio fischeri: a comparison of the acute effects of different formulations.

PubMed

Jacob, Raquel Sampaio; Santos, Lucilaine Valéria de Souza; de Souza, Ana Flávia Rodrigues; Lange, Liséte Celina

2016-11-01

Considerable quantities of different classes of drugs are consumed annually worldwide. These drugs, once disposed, often remain stable, even after conventional or advanced treatments. Although there have been a number of studies on the potential harm caused by drugs when released into the environment, few studies have investigated the toxicity of pharmaceutical excipients. In the present study, the acute toxicity of 30 drugs was tested to Aliivibrio fischeri. Ten different active ingredients were investigated, each in three distinct formulations: generic, similar and reference (brand drug). The aim of the study was to evaluate the harmful potential of drugs frequently sold in drugstores and to assess the contribution of excipients towards the observed acute toxicity. Within the 10 drugs evaluated, only one, dexchlorpheniramine maleate, was not toxic in any formulation. The toxicities of the three formulations were often different, even though the active ingredient has been the same. For some drugs, such as diazepam, glibenclamide, metformin, nimesulide, hydrochlorothiazide and simvastatin, only one or two of the three formulations tested were toxic to A. fischeri. These results highlight the toxicological potential of drug excipients, but not exclusively the toxicity of the active ingredients.

Heat effects on drug delivery across human skin

PubMed Central

Hao, Jinsong; Ghosh, Priyanka; Li, S. Kevin; Newman, Bryan; Kasting, Gerald B.; Raney, Sam G.

2016-01-01

Introduction Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin. Areas covered This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed. Expert opinion There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration. PMID:26808472

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

PubMed

Boyer, Arnaud; Pasquier, Eddy; Tomasini, Pascale; Ciccolini, Joseph; Greillier, Laurent; Andre, Nicolas; Barlesi, Fabrice; Mascaux, Celine

2018-03-31

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-income countries where access to expensive drugs is limited. This review assesses the published preclinical and clinical data about drug repurposing in MPM.In this review, we identified 11 therapeutic classes that could be repositioned in mesothelioma. Most of these treatments have been evaluated in vitro , half have been evaluated in vivo in animal models of MPM and only three ( i.e. valproate, thalidomide and zoledronic acid) have been investigated in clinical trials, with limited benefits so far. Efforts could be coordinated to pursue further investigations and test promising drugs identified in preclinical experiments in appropriately designed clinical trials. Copyright ©ERS 2018.

Agreement between PRE2DUP register data modeling method and comprehensive drug use interview among older persons

PubMed Central

Taipale, Heidi; Tanskanen, Antti; Koponen, Marjaana; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

2016-01-01

Background PRE2DUP is a modeling method that generates drug use periods (ie, when drug use started and ended) from drug purchases recorded in dispensing-based register data. It is based on the evaluation of personal drug purchasing patterns and considers hospital stays, possible stockpiling of drugs, and package information. Objective The objective of this study was to investigate person-level agreement between self-reported drug use in the interview and drug use modeled from dispensing data with PRE2DUP method for various drug classes used by older persons. Methods Self-reported drug use was assessed from the GeMS Study including a random sample of persons aged ≥75 years from the city of Kuopio, Finland, in 2006. Drug purchases recorded in the Prescription register data of these persons were modeled to determine drug use periods with PRE2DUP modeling method. Agreement between self-reported drug use on the interview date and drug use calculated from register-based data was compared in order to find the frequently used drugs and drug classes, which was evaluated by Cohen’s kappa. Kappa values 0.61–0.80 were considered to represent good and 0.81–1.00 as very good agreement. Results Among 569 participants with mean age of 82 years, the agreement between interview and register data was very good for 75% and very good or good for 93% of the studied drugs or drug classes. Good or very good agreement was observed for drugs that are typically used on regular bases, whereas “as needed” drugs represented poorer results. Conclusion PRE2DUP modeling method validly describes regular drug use among older persons. For most of drug classes investigated, PRE2DUP-modeled register data described drug use as well as interview-based data which are more time-consuming to collect. Further studies should be conducted by comparing it with other methods and in different drug user populations. PMID:27785101

A systematic review of modelling approaches in economic evaluations of health interventions for drug and alcohol problems.

PubMed

Hoang, Van Phuong; Shanahan, Marian; Shukla, Nagesh; Perez, Pascal; Farrell, Michael; Ritter, Alison

2016-04-13

The overarching goal of health policies is to maximize health and societal benefits. Economic evaluations can play a vital role in assessing whether or not such benefits occur. This paper reviews the application of modelling techniques in economic evaluations of drug and alcohol interventions with regard to (i) modelling paradigms themselves; (ii) perspectives of costs and benefits and (iii) time frame. Papers that use modelling approaches for economic evaluations of drug and alcohol interventions were identified by carrying out searches of major databases. Thirty eight papers met the inclusion criteria. Overall, the cohort Markov models remain the most popular approach, followed by decision trees, Individual based model and System dynamics model (SD). Most of the papers adopted a long term time frame to reflect the long term costs and benefits of health interventions. However, it was fairly common among the reviewed papers to adopt a narrow perspective that only takes into account costs and benefits borne by the health care sector. This review paper informs policy makers about the availability of modelling techniques that can be used to enhance the quality of economic evaluations for drug and alcohol treatment interventions.

Model for the evaluation of drug-dispensing services in primary health care

PubMed Central

Sartor, Vanessa de Bona; de Freitas, Sergio Fernando Torres

2014-01-01

OBJECTIVE To develop a model for evaluating the efficacy of drug-dispensing service in primary health care. METHODS An efficacy criterion was adopted to determine the level of achievement of the service objectives. The evaluation model was developed on the basis of a literature search and discussions with experts. The applicability test of the model was conducted in 15 primary health care units in the city of Florianópolis, state of Santa Catarina, in 2010, and data were recorded in structured and pretested questionnaires. RESULTS The model developed was evaluated using five dimensions of analysis for analysis. The model was suitable for evaluating service efficacy and helped to identify the critical points of each service dimension. CONCLUSIONS Adaptations to the data collection technique may be required to adjust for the reality and needs of each situation. The evaluation of the drug-dispensing service should promote adequate access to medications supplied through the public health system. PMID:25372174

The NICE recommendation for drug-coated balloons and its global impact.

PubMed

Eccleshall, Simon; Waliszewski, M

2015-06-01

The clinical efficacy and safety of drug-coated balloon (DCB) angioplasty in patients with coronary in-stent restenosis (ISR) has been demonstrated. The objective of this article is to provide comparative cost efficacy data for DCB angioplasty in various countries based on the original methodology of the Medical Technologies Evaluation Programme (MTEP) at the National Institute for Health and Clinical Excellence (NICE) in 2010. Published and unpublished Health Technology Assessment (HTA) reports were evaluated for comparison in selected countries. Furthermore, a systematic review of economic evaluations of DCB angioplasty versus standard treatments (uncoated balloon angioplasty or drug-eluting stent implantations) was conducted. National cost efficacy data were evaluated using Markov state transition models which were adapted to fit each country's device and procedure related costs. The clinical input for adverse events was defined with two relevant trials for in-stent restenosis of bare metal stents (BMS-ISR) and of drug-eluting stents (DES-ISR). In the UK, Germany, Switzerland, South Africa, Japan and Brazil, DCB angioplasty is cost-effective when compared with drug-eluting stents to treat either BMS-ISR or DES-ISR. DCB angioplasty ought to be the preferred treatment option for patients with BMS-ISR and DES-ISR from the payers' point of view. © The Author(s), 2015.

Formulation characteristics and in vitro release testing of cyclosporine ophthalmic ointments.

PubMed

Dong, Yixuan; Qu, Haiou; Pavurala, Naresh; Wang, Jiang; Sekar, Vasanthakumar; Martinez, Marilyn N; Fahmy, Raafat; Ashraf, Muhammad; Cruz, Celia N; Xu, Xiaoming

2018-06-10

The aim of the present study was to investigate the relationship between formulation/process variables versus the critical quality attributes (CQAs) of cyclosporine ophthalmic ointments and to explore the feasibility of using an in vitro approach to assess product sameness. A definitive screening design (DSD) was used to evaluate the impact of formulation and process variables. The formulation variables included drug percentage, percentage of corn oil and lanolin alcohol. The process variables studied were mixing temperature, mixing time and the method of mixing. The quality and performance attributes examined included drug assay, content uniformity, image analysis, rheology (storage modulus, shear viscosity) and in vitro drug release. Of the formulation variables evaluated, the percentage of the drug substance and the percentage of corn oil in the matrix were the most influential factors with respect to in vitro drug release. Conversely, the process parameters tested were observed to have minimal impact. An evaluation of the release mechanism of cyclosporine from the ointment revealed an interplay between formulation (e.g. physicochemical properties of the drug and ointment matrix type) and the release medium. These data provide a scientific basis to guide method development for in vitro drug release testing of ointment dosage forms. These results demonstrate that the in vitro methods used in this investigation were fit-for-purpose for detecting formulation and process changes and therefore amenable to assessment of product sameness. Published by Elsevier B.V.

Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches

PubMed Central

Kim, Marlene; Sedykh, Alexander; Chakravarti, Suman K.; Saiakhov, Roustem D.; Zhu, Hao

2014-01-01

Purpose Oral bioavailability (%F) is a key factor that determines the fate of a new drug in clinical trials. Traditionally, %F is measured using costly and time -consuming experimental tests. Developing computational models to evaluate the %F of new drugs before they are synthesized would be beneficial in the drug discovery process. Methods We employed Combinatorial Quantitative Structure-Activity Relationship approach to develop several computational %F models. We compiled a %F dataset of 995 drugs from public sources. After generating chemical descriptors for each compound, we used random forest, support vector machine, k nearest neighbor, and CASE Ultra to develop the relevant QSAR models. The resulting models were validated using five-fold cross-validation. Results The external predictivity of %F values was poor (R2=0.28, n=995, MAE=24), but was improved (R2=0.40, n=362, MAE=21) by filtering unreliable predictions that had a high probability of interacting with MDR1 and MRP2 transporters. Furthermore, classifying the compounds according to the %F values (%F<50% as “low”, %F≥50% as ‘high”) and developing category QSAR models resulted in an external accuracy of 76%. Conclusions In this study, we developed predictive %F QSAR models that could be used to evaluate new drug compounds, and integrating drug-transporter interactions data greatly benefits the resulting models. PMID:24306326

In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion.

PubMed

Saerens, Lien; Dierickx, Lien; Quinten, Thomas; Adriaensens, Peter; Carleer, Robert; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas

2012-05-01

The aim was to evaluate near-infrared spectroscopy for the in-line determination of the drug concentration, the polymer-drug solid-state behaviour and molecular interactions during hot-melt extrusion. Kollidon® SR was extruded with varying metoprolol tartrate (MPT) concentrations (20%, 30% and 40%) and monitored using NIR spectroscopy. A PLS model allowed drug concentration determination. The correlation between predicted and real MPT concentrations was good (R(2)=0.97). The predictive performance of the model was evaluated by the root mean square error of prediction, which was 1.54%. Kollidon® SR with 40% MPT was extruded at 105°C and 135°C to evaluate NIR spectroscopy for in-line polymer-drug solid-state characterisation. NIR spectra indicated the presence of amorphous MPT and hydrogen bonds between drug and polymer in the extrudates. More amorphous MPT and interactions could be found in the extrudates produced at 135°C than at 105°C. Raman spectroscopy, DSC and ATR FT-IR were used to confirm the NIR observations. Due to the instability of the formulation, only in-line Raman spectroscopy was an adequate confirmation tool. NIR spectroscopy is a potential PAT-tool for the in-line determination of API concentration and for the polymer-drug solid-state behaviour monitoring during pharmaceutical hot-melt extrusion. Copyright © 2012 Elsevier B.V. All rights reserved.

Formulation and process factors influencing product quality and in vitro performance of ophthalmic ointments.

PubMed

Xu, Xiaoming; Al-Ghabeish, Manar; Rahman, Ziyaur; Krishnaiah, Yellela S R; Yerlikaya, Firat; Yang, Yang; Manda, Prashanth; Hunt, Robert L; Khan, Mansoor A

2015-09-30

Owing to its unique anatomical and physiological functions, ocular surface presents special challenges for both design and performance evaluation of the ophthalmic ointment drug products formulated with a variety of bases. The current investigation was carried out to understand and identify the appropriate in vitro methods suitable for quality and performance evaluation of ophthalmic ointment, and to study the effect of formulation and process variables on its critical quality attributes (CQA). The evaluated critical formulation variables include API initial size, drug percentage, and mineral oil percentage while the critical process parameters include mixing rate, temperature, time and cooling rate. The investigated quality and performance attributes include drug assay, content uniformity, API particle size in ointment, rheological characteristics, in vitro drug release and in vitro transcorneal drug permeation. Using design of experiments (DoE) as well as a novel principle component analysis approach, five of the quality and performance attributes (API particle size, storage modulus of ointment, high shear viscosity of ointment, in vitro drug release constant and in vitro transcorneal drug permeation rate constant) were found to be highly influenced by the formulation, in particular the strength of API, and to a lesser degree by processing variables. Correlating the ocular physiology with the physicochemical characteristics of acyclovir ophthalmic ointment suggested that in vitro quality metrics could be a valuable predictor of its in vivo performance. Published by Elsevier B.V.

An Examination of Income Effect on Consumers' Ethical Evaluation of Counterfeit Drugs Buying Behaviour: A Cross-Sectional Study in Qatar and Sudan.

PubMed

Alfadl, Abubakr Abdelraouf; Ibrahim, Mohamed Izham Mohamed; Maraghi, Fatima Abdulla; Mohammad, Khadijah Shhab

2016-09-01

There are limited studies on consumer behaviour toward counterfeit products and the determining factors that motivate willingness to purchase counterfeit items. This study aimed to fill this literature gap through studying differences in individual ethical evaluations of counterfeit drug purchase and whether that ethical evaluation affected by difference in income. It is hypothesized that individuals with lower/higher income make a more/less permissive evaluation of ethical responsibility regarding counterfeit drug purchase. To empirically test the research assumption, a comparison was made between people who live in the low-income country Sudan and people who live in the high-income country Qatar. The study employed a face-to-face structured interview survey methodology to collect data from 1,170 subjects and the Sudanese and Qatari samples were compared using independent t-test at alpha level of 0.05 employing SPSS version 22.0. Sudanese and Qatari individuals were significantly different on all items. Sudanese individuals scored below 3 for all Awareness of Societal Consequences (ASC) items indicating that they make more permissive evaluation of ethical responsibility regarding counterfeit drug purchase. Both groups shared a basic positive moral agreement regarding subjective norm indicating that influence of income is not evident. Findings indicate that low-income individuals make more permissive evaluation of ethical responsibility regarding counterfeit drugs purchase when highlighting awareness of societal consequences used as a deterrent tool, while both low and high-income individuals share a basic positive moral agreement when subjective norm dimension is exploited to discourage unethical buying behaviour.

Drug development in neuropsychopharmacology.

PubMed

Fritze, Jürgen

2008-03-01

Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

A humanized mouse model for HIV-2 infection and efficacy testing of a single-pill triple-drug combination anti-retroviral therapy.

PubMed

Hu, Shuang; Neff, Charles Preston; Kumar, Dipu Mohan; Habu, Yuichiro; Akkina, Sarah R; Seki, Takahiro; Akkina, Ramesh

2017-01-15

While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, Triumeq R ). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis. Oral drug treatment led to full viral suppression and protection from CD4 T cell depletion. Cessation of therapy resulted in viral rebound and CD4 T cell loss. These proof-of-concept studies establish the utility of hu-mice for evaluating HIV-2 pathogenesis in more detail in the future, testing novel therapies and providing pre-clinical efficacy data of a three drug combination to treat HIV-2 infections. Copyright © 2016. Published by Elsevier Inc.

Drug induced hypertension--An unappreciated cause of secondary hypertension.

PubMed

Grossman, Alon; Messerli, Franz H; Grossman, Ehud

2015-09-15

Most patients with hypertension have essential hypertension or well-known forms of secondary hypertension, such as renal disease, renal artery stenosis, or common endocrine diseases (hyperaldosteronism or pheochromocytoma). Physicians are less aware of drug induced hypertension. A variety of therapeutic agents or chemical substances may increase blood pressure. When a patient with well controlled hypertension is presented with acute blood pressure elevation, use of drug or chemical substance which increases blood pressure should be suspected. Drug-induced blood pressure increases are usually minor and short-lived, although rare hypertensive emergencies associated with use of certain drugs have been reported. Careful evaluation of prescription and non-prescription medications is crucial in the evaluation of the hypertensive individual and may obviate the need for expensive and unnecessary evaluations. Discontinuation of the offending agent will usually achieve adequate blood pressure control. When use of a chemical agent which increases blood pressure is mandatory, anti-hypertensive therapy may facilitate continued use of this agent. We summarize the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. Copyright © 2015 Elsevier B.V. All rights reserved.

A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods

PubMed Central

Chinna Reddy, P; Chaitanya, K.S.C.; Madhusudan Rao, Y.

2011-01-01

Owing to the ease of the administration, the oral cavity is an attractive site for the delivery of drugs. Through this route it is possible to realize mucosal (local effect) and transmucosal (systemic effect) drug administration. In the first case, the aim is to achieve a site-specific release of the drug on the mucosa, whereas the second case involves drug absorption through the mucosal barrier to reach the systemic circulation. The main obstacles that drugs meet when administered via the buccal route derive from the limited absorption area and the barrier properties of the mucosa. The effective physiological removal mechanisms of the oral cavity that take the formulation away from the absorption site are the other obstacles that have to be considered. The strategies studied to overcome such obstacles include the employment of new materials that, possibly, combine mucoadhesive, enzyme inhibitory and penetration enhancer properties and the design of innovative drug delivery systems which, besides improving patient compliance, favor a more intimate contact of the drug with the absorption mucosa. This presents a brief description of advantages and limitations of buccal drug delivery and the anatomical structure of oral mucosa, mechanisms of drug permeation followed by current formulation design in line with developments in buccal delivery systems and methodology in evaluating buccal formulations. PMID:23008684

Toward a normalized clinical drug knowledge base in China-applying the RxNorm model to Chinese clinical drugs.

PubMed

Wang, Li; Zhang, Yaoyun; Jiang, Min; Wang, Jingqi; Dong, Jiancheng; Liu, Yun; Tao, Cui; Jiang, Guoqian; Zhou, Yi; Xu, Hua

2018-07-01

In recent years, electronic health record systems have been widely implemented in China, making clinical data available electronically. However, little effort has been devoted to making drug information exchangeable among these systems. This study aimed to build a Normalized Chinese Clinical Drug (NCCD) knowledge base, by applying and extending the information model of RxNorm to Chinese clinical drugs. Chinese drugs were collected from 4 major resources-China Food and Drug Administration, China Health Insurance Systems, Hospital Pharmacy Systems, and China Pharmacopoeia-for integration and normalization in NCCD. Chemical drugs were normalized using the information model in RxNorm without much change. Chinese patent drugs (i.e., Chinese herbal extracts), however, were represented using an expanded RxNorm model to incorporate the unique characteristics of these drugs. A hybrid approach combining automated natural language processing technologies and manual review by domain experts was then applied to drug attribute extraction, normalization, and further generation of drug names at different specification levels. Lastly, we reported the statistics of NCCD, as well as the evaluation results using several sets of randomly selected Chinese drugs. The current version of NCCD contains 16 976 chemical drugs and 2663 Chinese patent medicines, resulting in 19 639 clinical drugs, 250 267 unique concepts, and 2 602 760 relations. By manual review of 1700 chemical drugs and 250 Chinese patent drugs randomly selected from NCCD (about 10%), we showed that the hybrid approach could achieve an accuracy of 98.60% for drug name extraction and normalization. Using a collection of 500 chemical drugs and 500 Chinese patent drugs from other resources, we showed that NCCD achieved coverages of 97.0% and 90.0% for chemical drugs and Chinese patent drugs, respectively. Evaluation results demonstrated the potential to improve interoperability across various electronic drug systems in China.

Human abuse liability evaluation of CNS stimulant drugs.

PubMed

Romach, Myroslava K; Schoedel, Kerri A; Sellers, Edward M

2014-12-01

Psychoactive drugs that increase alertness, attention and concentration and energy, while also elevating mood, heart rate and blood pressure are referred to as stimulants. Despite some overlapping similarities, stimulants cannot be easily categorized by their chemical structure, mechanism of action, receptor binding profile, effects on monoamine uptake, behavioral pharmacology (e.g., effects on locomotion, temperature, and blood pressure), therapeutic indication or efficacy. Because of their abuse liability, a pre-market assessment of abuse potential is required for drugs that show stimulant properties; this review article focuses on the clinical aspects of this evaluation. This includes clinical trial adverse events, evidence of diversion or tampering, overdoses and the results of a human abuse potential study. While there are different types of human experimental studies that can be employed to evaluate stimulant abuse potential (e.g., drug discrimination, self-administration), only the human abuse potential study and clinical trial adverse event data are required for drug approval. The principal advances that have improved human abuse potential studies include using study enrichment strategies (pharmacologic qualification), larger sample sizes, better selection of endpoints and measurement strategies and more carefully considered interpretation of data. Because of the methodological advances, comparisons of newer studies with historical data is problematic and may contribute to a biased regulatory framework for the evaluation of newer stimulant-like drugs, such as A2 antagonists. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.