Explore the vast range of titles available.

Background The independent oversight of clinical trials, which is recommended by the Medical Research Council (MRC) Guidelines for Good Clinical Practice, is typically provided by an independent advisory Data Monitoring Committee (DMC) and an independent executive committee, to whom the DMC makes recommendations. The detailed roles and function of this executive committee, known as the Trial Steering Committee (TSC), have not previously been studied or reviewed since those originally proposed by the MRC in 1998. Methods An expert panel (n = 7) was convened comprising statisticians, clinicians and trial methodologists with prior TSC experience. Twelve questions about the role and responsibilities of the TSC were discussed by the panel at two full-day meetings. Each meeting was transcribed in full and the discussions were summarised. Results The expert panel reached agreement on the role of the TSC, to which it was accountable, the membership, the definition of independence, and the experience and training needed. The management of ethical issues, difficult/complex situations and issues the TSC should not ask the DMC to make recommendations on were more difficult to discuss without specific examples, but support existed for further work to help share issues and to provide appropriate training for TSC members. Additional topics discussed, which had not been identified by previous work relating to the DMCs but were pertinent to the role of the TSC, included the following: review of data sharing requests, indemnity, lifespan of the TSC, general TSC administration, and the roles of both the Funder and the Sponsor. Conclusions This paper presents recommendations that will contribute to the revision and update of the MRC TSC terms of reference. Uncertainty remains in some areas due to the absence of real-life examples; future guidance on these issues would benefit from a repository of case studies. Notably, the role of a patient and public involvement (PPI) contributor was not discussed, and further work is warranted to explore the role of a PPI contributor in independent trial oversight.

Data safety and monitoring boards are part of many clinical trials. This Sounding Board article addresses the ethical issues facing board members when they make a decision to stop a clinical trial early or to continue it in the face of evidence that one treatment is more effective than another. Data safety and monitoring boards, also known by other names (e.g., data monitoring committees), were first introduced in the 1960s as a mechanism for monitoring interim data in clinical trials in order to ensure the safety of the participating subjects. The key concept was to recruit board members who were expert in the field of interest but not otherwise intimately involved in the study (that is, not organizers, sponsors, or investigators), so that they could be objective in their assessment of issues that arose during the study. Over the past decade, the use of data and safety monitoring boards has . . .

Background International guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned. Methods It was a documentary review of all approved clinical trial protocols that were submitted at the Cameroon National Ethics Committee for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety. Results In total, 106 (4.9 %) clinical trial protocols were identified from 2173 protocols seen in the archive and 104 (4.8 %) included for review. Seventy six (73.1 %) trials did not include the surveillance of adverse events as part of their objective. A total of 91 (87.5 %) protocols did not budget for adverse event surveillance, 76 (73.1 %) did not have a data safety management board (DSMB), 11(10.6 %) included insurance for participants, 47 (45.2 %) did not include a case definition for serious adverse events, 33 (31.7 %) described procedures to detect adverse events, 33 (31.7 %) described procedure for reporting and 22 (21.2 %) described procedure for investigating adverse events. Discussions Most clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols. Conclusion Clinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan to assess adverse events in clinical trial protocols. In order to improve on the safety of participants and marketed drug, there is a need to develop national guidelines for clinical trials by the government, and to improve evaluation procedures and monitoring of ongoing trials by the ethics committee.

Over the past three decades it has become increasingly recognized that systematic assessment of as high a proportion as possible of relevant research evidence is needed to protect the best interests of patients and the public. For example, this principle is manifested in clinical guidelines and, increasingly, in the design and monitoring of new research. For scientific and ethical reasons, those responsible for monitoring the progress of ongoing clinical trials may need to seek unpublished and interim data to protect the interests of actual or potential participants in research. The challenge facing data monitoring committees has received relatively little attention, however. In this paper we review some of the commentaries on the issue and the few accounts of actual data monitoring committee experiences. We then present details of our own recent experience as members of the data monitoring committee for the BOOST-II UK trial (ISRCTN:0084226), one of five concurrent trials assessing the level of arterial oxygen which should be targeted in the care of very premature neonates. We conclude that efficient protection both of the interests of actual or potential participants in research and of science requires that data monitoring committees have access to all relevant research, including unpublished and interim data.

US oversight of clinical trials found wanting.

1 Several research ethics codes reiterate the necessity for informed consent throughout the research process.'s Although the quality of information provided to potential participants at the time of trial initiation has received much attention,6-8 there has been relatively little discussion, and no consensus, about the delivery and adequacy of information provided to individuals after their enrolment.9 This concern applies particularly to large randomised controlled trials, in which consideration of new information is often delegated to a data-monitoring committee. Whether statistical significance (valued by the committee in the finasteride study) represents an acceptable threshold for sharing information of potential importance (as promised in US federal regulations) is not self-evident.\\n Other reports highlight the extent to which decisions to disclose information, or to stop a trial early, can be controversial.17,20 Although the data-monitoring committee is expected to have to make difficult decisions, consideration should be given to creation of a mechanism for consultation with outside experts for advice, recommendation, or decision when the appointed members (or a substantial minority of members) feel there is sufficient disagreement within the group.

Clinical trials have become a major research tool to evaluate new medical interventions. Most trials require some level of data monitoring for quality control and many trials require special monitoring for participant safety. For national multicenter trials, independent data monitoring committees have become the standard for monitoring for evidence of participant benefit or harm in trials with irreversible outcomes such as death or serious morbidity. The Institutional Review Board (IRB) is held responsible for monitoring local trials. Often local institutions do not have an infrastructure in place to meet this responsibility, and therefore local IRBs cannot fulfill this obligation. In addition, IRBs are currently inundated with individual safety reports from local and multi-institutional trials which may appear to provide some level of safety monitoring, but in fact gives a false sense of security. We propose the establishment of institutional data monitoring committees and appropriate informatics infrastructure to monitor local trials.

Enhanced Supression of the Platelet IIb/IIIa Receptor with Integrilin Trial (ESPRIT) was a multicenter randomized controlled clinical trial in which participants were randomized between eptifibatide and placebo. A “clinical hold” was initially placed on the trial by the US Food and Drug Administration (FDA), which was concerned about the placebo-only control arm. The hold was lifted after additional information concerning the use of platelet glycoprotein IIb/IIIa inhibitors in clinical practice, derived from a survey of interventional cardiologists, was provided. The trial's principal investigator and colleagues have described how these issues were resolved, and advance a claim of equipoise for the trial. In this critical appraisal we examine the information and arguments proffered in support of the trial design and conclude that they evidence a misunderstanding of equipoise. We believe that a placebo-only control arm was not justified by the information provided by the trialists.

The responsibility for reports about drug trials in medical journals should lie with the clinicians in the steering committee, not with the industrial sponsor. Examples of undue influence of sponsors on the conduct and analysis are the choice of surrogate outcome events, changes in the protocol during the trial, discontinuation of the study, post hoc analyses and suppression of publication. Since this essay was written, the International Committee of Medical Journal Editors (‘Vancouver Group’) has issued the condition that authors of submitted manuscripts should guarantee their independence in data analysis and reporting. Nevertheless, this ‘security check’ occurs at a late stage and may not apply to journals that are less well known. Institutional Review Boards should routinely take the matter of independence into account. Also, European guidelines should be rewritten to reflect these fundamental issues rather than a multitude of details. In fact not sponsors or physicians but patients and the general public are the true owners of trial data.