DOCSLIB.ORG

Placebo-Controlled Trials of New Drugs: Ethical Considerations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Placebo-Controlled Trials of New Drugs: Ethical Considerations Reviews/Commentaries/Position Statements COMMENTARY Placebo-Controlled Trials of New Drugs: Ethical Considerations DAVID ORENTLICHER, MD, JD als, placebo controls are not appropriate when patients’ health would be placed at significant risk (8–10). A placebo- controlled study for a new hair- uch controversy exists regarding sufficiently more effective than placebo to thickening agent could be justified; a the ethics of placebo-controlled justify its use. Finally, not all established placebo-controlled study for patients M trials in which an experimental therapies have been shown to be superior with moderate or severe hypertension therapy will compete with an already es- to placebo. If newer drugs are compared would not be acceptable (11). Similarly, if tablished treatment (or treatments). In with the unproven existing therapies, an illness causes problems when it goes such cases, argue critics, patients in the then patients may continue to receive untreated for a long period of time, a 52- control arm of the study should receive an drugs that are harmful without being week study with a placebo control is accepted therapy rather than a placebo. helpful. much more difficult to justify than a By using an active and effective drug, the Moreover, say proponents of placebo 6-week study (12). control patients would not be placed at controls, patients can be protected from When David S.H. Bell (13) explains risk for deterioration of their disease, and harm by “escape” criteria, which call for why placebo controls are unacceptable the study would generate more meaning- withdrawal from the trial if the patient for new drugs to treat type 2 diabetes, he ful results for physicians. The key question, shows evidence of inadequately con- makes arguments that would resonate it is said, is not whether a new therapy is trolled disease (5). Other changes in study with proponents as well as opponents of better than nothing but whether it is bet- design can also be used to minimize the placebo controls. As he observes, patients in ter than the current standard of care (1,2). risk to patients from exposure to placebos a placebo arm of a study could go 6 months In response, say proponents of place- (7). without effective therapy and thereby suf- bo-controlled trials, critical information Yet for all of the controversy over pla- fer significant and irreversible harm. cannot always be obtained by giving con- cebo-controlled studies, the amount of Still, the very fact that Bell has written trol patients an existing therapy. For some agreement may be greater than the his letter points to a serious concern with effective therapies, the drug may perform amount of disagreement. For many stud- placebo-controlled trials. Apparently, no better than placebo in a particular trial ies, people on both sides of the issue many are conducted even though they even though other trials demonstrate the would agree that a placebo control is ei- cannot be justified in terms of widely drug’s superiority to placebo. If an exper- ther necessary or unacceptable. It is only shared views about the ethical appropri- imental agent confers the same benefit as in a fairly limited area of concern in which ateness of such trials (2). such an existing therapy in a comparative commenters part ways. There are probably multiple reasons trial, we cannot be certain that the new Thus, for example, opponents of pla- for the overuse of placebo controls. Phar- agent is any better than placebo. We cebo-controlled trials recognize that pla- maceutical companies may believe it is in might have one of the trials in which the cebo controls are justified for “first- their interest to compare new drugs with existing therapy (and therefore the new generation” drugs—drugs designed to fill placebo rather than existing therapy, even agent) does no better than placebo, per- a gap in the therapeutic armamentarium. when better information for patients and haps because of inadequate sample size, Relatedly, placebo controls are often jus- physicians would be provided by an ac- perhaps because the outcome measure tified when there is not adequate evidence tive control. There also appears to be can vary widely from one patient group to to support the efficacy of existing therapy. some misunderstanding of the U.S. Food another (3–5). In addition, some new Just as opponents of placebo controls and Drug Administration’s (FDA’s) posi- therapies are useful even if they are less accept some uses of placebos, proponents tion on the need for placebo controls effective than existing therapies. Some pa- of placebo controls support some limits and/or some overly aggressive requiring tients might choose a less effective drug if on placebo-controlled trials. Basic princi- of placebo-controlled studies by the FDA. substantial cost savings or a reduction in ples of medical ethics tell us that clinical Whether the FDA is truly at fault is not side effects would be realized (6). With- studies can go forward only if the ex- always obvious. One article, for example, out a placebo control, however, one can- pected benefits sufficiently outweigh the criticized the FDA for demanding a place- not always tell whether a new drug that is expected risks. Accordingly, acknowledge bo-controlled trial of a new anti-anginal not as effective as existing therapy is still the proponents of placebo-controlled tri- drug, despite a study demonstrating that ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● the drug was comparable to propranolol From the Center for Law and Health, Indiana University School of Law-Indianapolis, and the Indiana as an anti-anginal agent (2). According to University School of Medicine, Indianapolis, Indiana. the FDA, however, the problem with the Address correspondence and reprint requests to Dr. David Orentlicher, Indiana University School of study was not necessarily its failure to use Law-Indianapolis, 735 W. New York St. (530 W. New York St. as of 7 May 2001), Indianapolis, IN 46202. E-mail: [email protected]. a placebo arm. Rather, the study design Received and accepted for publication 23 January 2001. was defective because it left open the pos- Abbreviations: FDA, U.S. Food and Drug Administration; IRB, institutional review board. sibility that neither the new drug nor pro- DIABETES CARE, VOLUME 24, NUMBER 4, APRIL 2001 771 Commentary pranolol was more effective than placebo ing placebo controls, that a placebo- References in that particular trial (8). controlled study can often be completed 1. Hill AB: Medical ethics and controlled tri- Where do we go from here? Undoubt- with fewer subjects and in a shorter pe- als. BMJ 1:1043–1049, 1963 edly, study sponsors and investigators riod of time (14). Costs are not irrele- 2. Rothman KJ, Michels KB: The continuing need to improve their understanding of vant—more expensive studies may mean unethical use of placebo controls. N Engl the extent to which placebo controls have fewer desirable studies—but arguments J Med 331:394–398, 1994 a role in clinical trials. Some studies with about costs cannot be accepted automat- 3. Makuch R, Johnson M: Issues in planning a placebo control should have an active ically. If an IRB is to make judgments on and interpreting active control equiva- control instead; other studies with only an cost grounds, the board would need spe- lence studies. J Clin Epidemiol 42:503– active control also need an arm with a cific information about the costs of the 511, 1989 placebo control. proposed and alternative studies. Indeed, 4. Tramer MR, Reynolds DJM, Moore RA, In addition, institutional review as a general matter, common arguments McQuay HJ: When placebo controlled tri- boards (IRBs) need to demand more of in favor of placebo controls are not ade- als are essential and equivalence trials are study investigators who submit proposals quate to justify a particular use of a pla- inadequate. BMJ 317:875–880, 1998 for trials of new drugs. If a placebo arm is cebo control. Rather, the arguments 5. Temple R, Ellenberg SS: Placebo-con- included for a drug that will compete with would have to be based on the specifics of trolled trials and active-control trials in an established treatment, the study proto- the study in question. the evaluation of new treatments. I. Ethi- col must supply a persuasive justification In deciding whether study investiga- cal and scientific issues. Ann Intern Med for using a placebo control (2). Similarly, tors have persuasive justification for in- 133:455–463, 2000 if a placebo arm is not included, there cluding or excluding a placebo control, 6. Miller FG: Placebo-controlled trials in psychiatric research: an ethical perspec- must be assurances that the study is de- IRBs should rely on one of the federal gov- tive. Biol Psychiatry 47:707–716, 2000 signed to avoid the possibility that the ernment’s basic requirements for medical 7. Amery W, Dony J: A clinical trial design new and active drugs show equal effec- research, a requirement that is too often avoiding undue placebo treatment. J Clin tiveness but that neither drug would be overlooked. According to regulations for Pharmacol 15:674–679, 1975 more effective than placebo in that study. the “Protection of Human Subjects,” not 8. Temple R: Government viewpoint of clin- IRBs, in other words, must approach only must studies have a favorable bene- ical trials. Drug Information J 16:10–17, studies of new drugs more skeptically and fit-to-risk ratio, but they must be de- 1982 approve studies only when they have signed so as to have the most favorable 9. Freedman B, Glass KC, Weijer C: Placebo enough information to make an indepen- benefit-to-risk ratio possible. In the lan- orthodoxy in clinical research.
Load more

Recommended publications
  • Homeopathy and Psychological Therapies
    Entry Homeopathy and Psychological Therapies Davide Donelli * and Michele Antonelli AUSL-IRCCS Reggio Emilia, 42122 Reggio Emilia, Italy; [email protected] * Correspondence: [email protected] Definition: Homeopathy is a popular, although highly debated, medicinal practice based on the administration of remedies in which active substances are so diluted that no detectable trace of them remains in the final product. This hypothesis paper aims to outline a possible reinterpreta- tion of homeopathy in the light of psychological therapies in order to improve its clinical safety and sustainability. Keywords: homeopathy; psychology; reinterpretation; hypothesis 1. Introduction Homeopathy is a popular, although highly debated, medicinal practice. In Italy, for ex- ample, it is estimated that, even if with a slightly declining trend, around 4.1% of the entire population (almost 2.5 million people) occasionally or regularly seeks homeopathic care, and these data, collected in 2013, suggest that homeopathy is the most used Complemen- tary and Alternative Medicine (CAM) by Italians [1]. Epidemiological studies aimed to assess the worldwide prevalence of homeopathy use have reported similar data for other high-income countries [2]. Homeopathy was first invented by the German doctor Samuel Hahnemann (1755–1843), and it is based on the administration of remedies in which active substances are so diluted that no detectable trace of them remains in the final product [3]. In his empirical studies, Citation: Donelli, D.; Antonelli, M. Hahnemann reported that the self-administration of a common antimalarial medicinal Homeopathy and Psychological Ther- plant (Cinchona) resulted in the occurrence of the same symptoms of malaria, but to a Encyclopedia 2021 1 apies.
    [Show full text]
  • Ocps) Used in the NM Family Planning Program (FPP
    The following slides are intended to familiarize nurses and clinicians with oral contraceptive pills (OCPs) used in the NM Family Planning Program (FPP). The FPP does not intend for this information to supersede the Family Planning Protocol particularly on the requirement for Public Health Nurses in the Public Health Offices to consult a clinician as stated in the Protocol when in doubt or if it is necessary to switch the client’s OCP type. 1 2 Combined oral contraceptives (COCs) contain two hormones; estrogen and progestin. In general, any combined OCP is good for most women who are eligible to take estrogen according to the CDC U.S. Medical Eligibility Criteria (MEC). Once again, refer to the US MEC chart to find out if OCP is a suitable choice for clients with specific health conditions. To learn a little bit about what each hormone does, the FPP is providing the following summary: Estrogen: provides endometrial stability = menstrual cycle control. A higher estrogen dose increases the venous thromboembolism (VTE) or clot risk but OCP clot risk is still less harmful than the clot risk related to pregnancy and giving birth. Progestin: provides most of the contraceptive effect by ‐Preventing luteinizing hormone (LH) surge /ovulation ‐Thickening the cervical mucus to prevent sperm entry. Two major OCP formations are available. Monophasic: There is only one dose of estrogen and progestin in each active pill in the packet; and Multiphasic: There are varying doses of hormones, particularly progestin in the active pills. 3 Section 3 of the FPP Protocol contains the OCP Substitute Table, which groups OCPs into 6 classes according to the estrogen dosage, the type of progestin and the formulations.
    [Show full text]
  • Nicotine and Behavioral Markers of Risk for Schizophrenia: a Double-Blind, Placebo- Controlled, Cross-Over Study Lana Dépatie, M.Sc., Gillian A
    Nicotine and Behavioral Markers of Risk for Schizophrenia: A Double-Blind, Placebo- Controlled, Cross-Over Study Lana Dépatie, M.Sc., Gillian A. O’Driscoll, Ph.D., Anne-Lise V. Holahan, B.Sc., Victoria Atkinson, R.N., Joseph X. Thavundayil, M.D., N. Ng Ying Kin, Ph.D., and Samarthji Lal, M.D. We investigated the effect of nicotine on three behavioral groups. A Drug ϫ Monitoring condition interaction (p Ͻ .01) markers of risk for schizophrenia: sustained attention on pursuit gain indicated that nicotine significantly (using the Continuous Performance Task (CPT)), increased pursuit gain in the no-monitoring condition in antisaccade performance, and smooth pursuit. Smooth patients and controls equally, but did not improve pursuit pursuit was investigated in two conditions, one in which in the monitoring condition. Thus, improvement in pursuit attention was enhanced (monitoring target changes) and may have been mediated via an effect on attention rather one in which attention was not enhanced (no monitoring). than by an effect on oculomotor function per se. In patients, Patients with schizophrenia (n ϭ 15) and controls (n ϭ 14) the magnitude of improvement in attention on nicotine was were given a 14-mg nicotine patch in a double-blind, correlated with the improvement on eye movement tasks. placebo-controlled, crossover design and plasma nicotine Thus, nicotine improves performance on both attention and concentrations were monitored. Nicotine concentrations oculomotor markers of risk for schizophrenia, possibly via were similar in both groups. A Group ϫ Drug interaction common mechanisms. (p Ͻ .02) on CPT hits indicated that nicotine improved [Neuropsychopharmacology 27:1056–1070, 2002] sustained attention in patients but not in controls.
    [Show full text]
  • Demystifying the Placebo Effect
    City University of New York (CUNY) CUNY Academic Works All Dissertations, Theses, and Capstone Projects Dissertations, Theses, and Capstone Projects 9-2018 Demystifying the Placebo Effect Phoebe Friesen The Graduate Center, City University of New York How does access to this work benefit ou?y Let us know! More information about this work at: https://academicworks.cuny.edu/gc_etds/2775 Discover additional works at: https://academicworks.cuny.edu This work is made publicly available by the City University of New York (CUNY). Contact: [email protected] DEMYSTIFYING THE PLACEBO EFFECT by PHOEBE FRIESEN A dissertation submitted to the Graduate Faculty in Philosophy in partial fulfillment of the requirements for the degree of Doctor of Philosophy, The City University of New York 2018 © 2018 PHOEBE FRIESEN All Rights Reserved ii Demystifying the Placebo Effect by Phoebe Friesen This manuscript has been read and accepted for the Graduate Faculty in Philosophy in satisfaction of the dissertation requirement for the degree of Doctor of Philosophy. ___________ ____________________________________ Date [Peter Godfrey-Smith] Chair of Examining Committee ___________ ____________________________________ Date [Nickolas Pappas ] Executive Office Supervisory Committee: Peter Godfrey-Smith Jesse Prinz John Greenwood THE CITY UNIVERSITY OF NEW YORK iii ABSTRACT Demystifying the Placebo Effect by Phoebe Friesen Advisor: Peter Godfrey-Smith This dissertation offers a philosophical analysis of the placebo effect. After offering an overview of recent evidence concerning the phenomenon, I consider several prominent accounts of the placebo effect that have been put forward and argue that none of them are able to adequately account for the diverse instantiations of the phenomenon. I then offer a novel account, which suggests that we ought to think of the placebo effect as encompassing three distinct responses: conditioned placebo responses, cognitive placebo responses, and network placebo responses.
    [Show full text]
  • Certification Accredited Schools List
    = Academic Clinical Research Programs Which Currently Meet Waiver Requirements for the Academy of Clinical Research Professional (Updated October 15, 2015) This list includes academic clinical research programs which, as of the above date, have been evaluated and found to meet the current waiver requirements established by the Academy of Clinical Research Professionals (Academy) Board of Trustees. Programs that meet the waiver requirements allow a candidate to waive 1,500 hours of hands-on experience performing the Essential Duties of the program to which the candidate has made application. This list is not to be considered exhaustive and is not designed to represent all the academic offerings available. Appearance on this list is not to be construed as an endorsement of its content or format by the Academy or a guarantee that a candidate will be eligible for certification. All individuals interested in enrolling in a program of study should evaluate any program on the basis of his or her personal needs. (* - programs marked with an asterisk MAY be accepted but acceptance will be dependent on the complete listing of courses completed) Individuals seeking additional information about each program should contact the institution directly. Academic Institution Program Name ( Click Title for Web Navigation) Academy of Applied Pharmaceutical Sciences Clinical Research Diploma Program American University of Health Sciences Master of Science in Clinical Research Anoka-Ramsey Community College Clinical Research Professional - Certificate Graduate
    [Show full text]
  • Generating Real-World Evidence by Strengthening Real-World Data Sources
    Generating Real-World Evidence by Strengthening Real-World Data Sources Using “real-world evidence” to bring new “Every day, health care professionals are updating patients’ treatments to patients as part of the 21st electronic health records with data on clinical outcomes Century Cures Act (the “Cures Act”) is a key resulting from medical interventions used in routine clinical priority for the Department of Health and practice. As our experience with new medical products Human Services (HHS). Specifically, the Cures expands, our knowledge about how to best maximize their Act places focus on the use of real-world data benefits and minimize potential risks sharpens with each data to support regulatory decision-making, including point we gather. Every clinical use of a product produces data the approval of new indications for existing that can help better inform us about its safety and efficacy.” drugs in order to make drug development faster jacqueline corrigan-curay, md, jd and more efficient. As such, the Cures Act director of the office of medical policy in fda’s center for drug evaluation and research has tasked the Food and Drug Administration (FDA) to develop a framework and guidance for evaluating real-world evidence in the context of drug regulation.1 Under the FDA’s framework, real-world evidence (RWE) is generated by different study designs or analyses, including but not limited to, randomized trials like large simple trials, pragmatic trials, and observational studies. RWE is the clinical evidence about the use, potential benefits, and potential risks of a medical product based on an analysis of real-world data (RWD).
    [Show full text]
  • Homeopathy Is Marketed As a Safe, Natural and Holistic Treatment for a Range of Ailments and Illnesses, Including Another Way of Saying
    sense about... sense about... sense about... sense about... sense about... sense about...Homeo sense about... sense about...path sense about...yyy sense about... sense about... sense about... sense about... sense about... sense about... sense about... Homeopathy is marketed as a safe, natural and holistic treatment for a range of ailments and illnesses, including Another way of saying... arthritis, asthma, depression, eczema, diarrhoea, hayfever, 8lacebo 999 a prescription that is inert; that is, it does nothing, headaches, insomnia and toothache. Homeopathic products and like a sugar pill or water. From the Latin, 1 will please.) services have become a large industry. 8lacebo effect 9 an effect, biological, biochemical or Despite this, it has not been embraced by medical science. The physiological, that emerges from an inert treatment because scientific evidence shows that homeopathy acts only as a the patient believes it will work. See page 2 for how placebos work.) placebo and there is no scientific explanation of how it could work any other way. Not to be confused... HomeoHomeopathpathpathicic principles 8roven 999 0proving( is the method homeopaths use to determine the symptoms a substance causes with a view to Homeopathy is based on two beliefs: 1) like cures like; and 2) treating diseases with similar symptoms); after the process a the smaller the dose the more potent the cure. First, homeopaths substance is said to be 0proven(. Scientists use 0proven( to choose a substance that causes the same symptoms as the describe a statement that is, by logic, necessarily true. disease they want to treat. For example, the runny nose and watery eyes of a cold can be recreated by inhaling onion fumes, human and animal waste, dead plants, bacteria and minerals; it so onion juice can form the basis of a homeopathic preparation.
    [Show full text]
  • Studies of Staphylococcal Infections. I. Virulence of Staphy- Lococci and Characteristics of Infections in Embryonated Eggs * WILLIAM R
    Journal of Clinical Investigation Vol. 43, No. 11, 1964 Studies of Staphylococcal Infections. I. Virulence of Staphy- lococci and Characteristics of Infections in Embryonated Eggs * WILLIAM R. MCCABE t (From the Research Laboratory, West Side Veterans Administration Hospital, and the Department of Medicine, Research and Educational Hospitals, University of Illinois College of Medicine, Chicago, Ill.) Many of the determinants of the pathogenesis niques still require relatively large numbers of and course of staphylococcal infections remain staphylococci to produce infection (19). Fatal imprecisely defined (1, 2) despite their increas- systemic infections have been equally difficult to ing importance (3-10). Experimental infections produce in animals and have necessitated the in- in suitable laboratory animals have been of con- jection of 107 to 109 bacteria (20-23). A few siderable assistance in clarifying the role of host strains of staphylococci have been found that are defense mechanisms and specific bacterial virulence capable of producing lethal systemic infections factors with a variety of other infectious agents. with inocula of from 102 to 103 bacteria (24) and A sensitive experimental model would be of value have excited considerable interest (25-27). The in defining the importance of these factors in virulence of these strains apparently results from staphylococcal infections, but both humans and an unusual antigenic variation (27, 28) which, the usual laboratory animals are relatively re- despite its interest, is of doubtful significance in sistant. Extremely large numbers of staphylo- human staphylococcal infection, since such strains cocci are required to produce either local or sys- have been isolated only rarely from clinical in- temic infections experimentally.
    [Show full text]
  • Using Real-World Evidence to Accelerate Safe and Effective Cures Advancing Medical Innovation for a Healthier America June 2016 Leadership Senator William H
    Using Real-World Evidence to Accelerate Safe and Effective Cures Advancing Medical Innovation for a Healthier America June 2016 Leadership Senator William H. Frist, MD Former U.S. Senate Majority Leader Chair, FDA: Advancing Medical Innovation Bipartisan Policy Center Representative Bart Gordon Former Member, U.S. House of Representatives Chair, FDA: Advancing Medical Innovation Bipartisan Policy Center Advisory Committee Marc M. Boutin, JD Chief Executive Officer National Health Council Mark McClellan, MD, PhD Director, Robert J. Margolis Center for Health Policy Duke University Patrick Soon-Shiong, MD Chairman and Chief Executive Officer Institute for Advanced Health Andrew von Eschenbach, MD President Samaritan Health Initiatives 1 Sta G. William Hoagland Ann Gordon Senior Vice President Writer Bipartisan Policy Center Michael Ibara, PharmD Janet M. Marchibroda Independent Consultant Director, Health Innovation Initiative and Executive Director, CEO Council on Health and Innovation Bipartisan Policy Center Tim Swope Senior Policy Analyst Bipartisan Policy Center Sam Watters Administrative Assistant Bipartisan Policy Center 2 FDA: ADVANCING MEDICAL INNOVATION EFFORT The Bipartisan Policy Center’s initiative, FDA: Advancing Medical Innovation, is developing viable policy options to advance medical innovation and reduce the time and cost associated with the discovery, development, and delivery of safe and effective drugs and devices for patients in the United States. Key areas of focus include the following: Improving the medical product development process; Increasing regulatory clarity; Strengthening the Food and Drug Administration’s (FDA) ability to carry out its mission; Using information technology to improve health and health care; and Increasing investment in medical products to address unmet and public health needs.
    [Show full text]
  • Short List of Commonly Used Acronyms in Clinical Research
    Short List of Commonly Used Acronyms in Clinical Research ACRP Association of Clinical Research Professionals AE Adverse Event ADR Adverse Drug Reaction AMA American Medical Association BAA Business Associate Agreement BIND Biological IND CA Coverage Analysis CAP College of American Pathologists CBCTN Community Based Clinical Trials Network CCRA Certified Clinical Research Associate (ACRP) CCRC Certified Clinical Research Coordinator (ACRP) CCRT Center for Clinical Research & Technology CCRP Certified Clinical Research Professional (SoCRA) CDA Confidential Disclosure Agreement CDC Center for Disease Control CFR Code of Federal Regulations CIRBI Center for IRB Intelligence CITI Collaborative Institutional Training Initiative CLIA Clinical Laboratory Improvement Amendments CME Continuing Medical Education CMS Central Management System COI Conflict of Interest CRA Clinical Research Associate CRC Clinical Research Coordinator CREC Continuing Research Education Credit CRF Case Report Form CRO Clinical Research Organization CTA Clinical Trial Agreement CTSC Clinical & Translational Science Collaborative CV Curriculum Vitae DCF Data Correction Form / Data Clarification Form DEA Drug Enforcement Agency (law enforcement division of FDA) DHHS Department of Health and Human Services DOS Date of Service DSMB or Data and Safety Monitoring Board (Plan or Committee) DSMP/C EAB Ethical Advisory Board (similar to IRB, used by other nations) EDC Electronic Data Capture FDA Food and Drug Administration FDA-482 Notice of Inspection FDA-483 Notice of Adverse
    [Show full text]
  • A Framework to Assess Empirical Reproducibility in Biomedical Research Leslie D
    McIntosh et al. BMC Medical Research Methodology (2017) 17:143 DOI 10.1186/s12874-017-0377-6 RESEARCH ARTICLE Open Access Repeat: a framework to assess empirical reproducibility in biomedical research Leslie D. McIntosh1, Anthony Juehne1*, Cynthia R. H. Vitale2, Xiaoyan Liu1, Rosalia Alcoser1, J. Christian Lukas1 and Bradley Evanoff3 Abstract Background: The reproducibility of research is essential to rigorous science, yet significant concerns of the reliability and verifiability of biomedical research have been recently highlighted. Ongoing efforts across several domains of science and policy are working to clarify the fundamental characteristics of reproducibility and to enhance the transparency and accessibility of research. Methods: The aim of the proceeding work is to develop an assessment tool operationalizing key concepts of research transparency in the biomedical domain, specifically for secondary biomedical data research using electronic health record data. The tool (RepeAT) was developed through a multi-phase process that involved coding and extracting recommendations and practices for improving reproducibility from publications and reports across the biomedical and statistical sciences, field testing the instrument, and refining variables. Results: RepeAT includes 119 unique variables grouped into five categories (research design and aim, database and data collection methods, data mining and data cleaning, data analysis, data sharing and documentation). Preliminary results in manually processing 40 scientific manuscripts indicate components of the proposed framework with strong inter-rater reliability, as well as directions for further research and refinement of RepeAT. Conclusions: The use of RepeAT may allow the biomedical community to have a better understanding of the current practices of research transparency and accessibility among principal investigators.
    [Show full text]
  • Independent Data and Safety Oversigh for DMID Clinical Research
    Policy No.: National Institute of Allergy and DMID Policy-010 - NCRS 1.2 v 2.0 Infectious Diseases / Division of Independent Data and Safety Oversight Microbiology and Infectious for DMID Clinical Research Diseases/Office of Clinical Research Affairs Effective Date: 13-JUL-2016 Version: 2.0 1.0 Purpose: To describe the Division of Microbiology and Infectious Diseases (DMID) policy for establishing independent data and safety oversight for DMID-supported clinical research. 2.0 Scope: This policy applies to DMID-supported clinical research studies where there are concerns about participant safety or data integrity. These types of studies require independent safety assessment. 3.0 Policy: An appropriate safety oversight plan will be described in the protocol. If applicable, an appropriate independent safety charter for all clinical research commensurate with risks, the size, and complexity of the study will be prepared. This plan will provide a description of the review of safety and/or efficacy data to assess volunteer safety and data integrity. The plan will state the level of independent oversight necessary or that no independent oversight is required. For grant-funded clinical research that does not require a formal protocol, the awarded grant will serve as the document describing the appropriate level of oversight. 4.0 Background: NIH policy requires that each Institute and Center (IC) have a system for managing/implementing the appropriate oversight of the conduct of clinical trials that ensures the safety of participants and the validity and integrity of the data. DMID extends this requirement to other clinical research where there are safety concerns. Data and safety oversight provides independent and objective review of the overall conduct of the study.
    [Show full text]