Non-commercial vs. commercial clinical trials: a retrospective study of the applications submitted to a research ethics committee.

There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug-evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double-blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value.

Exclusion of pregnant women from industry-sponsored clinical trials.

OBJECTIVE: The lack of human data available to inform evidence-based treatment for illness during pregnancy has led to calls for greater inclusion of pregnant women in research, but the extent of their current representation is poorly characterized. Our objective was to measure the current exclusion of pregnant women from industry-sponsored clinical trials as a baseline for future comparison. METHODS: We compiled data from studies enrolling women of childbearing potential posted on www.ClinicalTrials.gov between 1 October 2011 and 31 January 2012. The review was limited to open United States-based phase IV interventional studies sponsored by the pharmaceutical industry evaluating treatment of conditions that may be experienced by but are not limited to pregnant women and did not involve a medication classified as potentially teratogenic. If there was no mention of pregnancy in the inclusion or exclusion criteria, we contacted a study representative to confirm that pregnant women could be enrolled. RESULTS: Of 558 qualifying industry-sponsored studies, five (1%) were designed specifically for pregnant women. Of 367 phase IV clinical trials with verified inclusion and exclusion criteria, 348 (95%) excluded pregnant women and 19 (5%) did not. CONCLUSION: We found the exclusion of pregnant women from industry-sponsored clinical trials to be common practice. Moving beyond reflexive exclusion and developing thoughtful criteria for inclusion of pregnant women in clinical research would likely advance the evidence base to inform treatment decisions during pregnancy and lead to better health outcomes for women and children.

[Patients' perspective and economic variables as objectives in clinical trials: added value to clinical parameters]. / Perspectiva de los pacientes y variables económicas como objetivo en los ensayos clínicos, valores añadidos a los parámetros clínicos.

OBJECTIVE: Patient-reported outcome (PRO) measures complement traditional biomedical outcome measures. The purpose of this study was to evaluate the use of PRO measures including health-related quality of life (HRQoL) questionnaires as a measurement of efficacy and the frequency of inclusion of economic variables related to direct and indirect costs in the design of clinical trials and phase IV observational studies. Moreover, for the trials quality score were measured, and if there were any relationship between the quality study design score and the PRO inclusion. MATERIAL AND METHODS: Retrospective observational study of the clinical trials and phase IV observational studies approved by a Clinical Research Ethics Committee (2008-2010). We gathered data concerning general aspects including medical specialty, pathology, methodological quality based on Jadad scale (0-5), inclusion of PRO and economic variables. For clinical trials including HRQoL measurements, we analysed the type of questionnaire in use. Where there were no HRQoL measurements, we analysed if their inclusion would have been proper or not. RESULTS: A total of 70 protocols (59 CTs and 11 phase IV observational studies) were analysed; 37 (52.8%) included PRO measures, and 3 protocols (4.3%) used them as a primary endpoint. Data analysis by therapeutic area showed that PRO measures were most commonly studied in the fields of endocrinology, neurology, digestive diseases, and cardiology. The average quality score for the trials was 2.8. The trials with more PRO inclusion in their end points had a significantly higher quality score. Only 13 (22%) clinical trials and 2 (18.2%) phase IV observational studies included economic variables. CONCLUSIONS: The emergence of economic variables in clinical trials and phase IV observational studies evaluated was low, however, more than half of the revised protocols have included PRO measures, reflecting the importance of these parameters in the assessment of the effectiveness of drug treatments, although its use is still not systematic.

A behavioral Bayes method to determine the sample size of a clinical trial considering efficacy and safety.

It is necessary for the calculation of sample size to achieve the best balance between the cost of a clinical trial and the possible benefits from a new treatment. Gittins and Pezeshk developed an innovative (behavioral Bayes) approach, which assumes that the number of users is an increasing function of the difference in performance between the new treatment and the standard treatment. The better a new treatment, the more the number of patients who want to switch to it. The optimal sample size is calculated in this framework. This BeBay approach takes account of three decision-makers, a pharmaceutical company, the health authority and medical advisers. Kikuchi, Pezeshk and Gittins generalized this approach by introducing a logistic benefit function, and by extending to the more usual unpaired case, and with unknown variance. The expected net benefit in this model is based on the efficacy of the new drug but does not take account of the incidence of adverse reactions. The present paper extends the model to include the costs of treating adverse reactions and focuses on societal cost-effectiveness as the criterion for determining sample size. The main application is likely to be to phase III clinical trials, for which the primary outcome is to compare the costs and benefits of a new drug with a standard drug in relation to national health-care.

[Difficulties with conducting clinical trials in France]. / Difficultés à la réalisation des essais cliniques en France.

France ranks third among European countries as regards the level of investment in clinical R&D and, overall, accounts for a contributive effort proportional to the size of its population and pharmaceutical market respectively. However, there is a trend for phase II and III studies to become proportionally fewer than in the past, while the number of phase IV studies is increasing. In a growing proportion of the mega-trials, which are instrumental for establishing evidence-based practice, French experts, investigators and, even more seriously, French patients, are insufficiently represented. Though studies in France are initiated relatively fast due to a clear regulatory framework and perform equally well as far as quantitative and qualitative factors are concerned, compared with most European countries involved in clinical research the costs incurred per completed patient are higher than those recorded in the other countries. Academic research shares most of these constraints and suffers from a lack of financial and human resources, while it faces additional delays in implementing studies because of longer administrative processes. Given the stakes in play, specific solutions should be implemented to maintain and further develop French competitiveness in clinical R&D. At the patient level, positive perception and awareness of the usefulness and safety of participating in clinical trials need to be emphasized. Education at the school level and using the lay media should be developed. Intervention of institutional and government officials is much needed. Direct patient recruitment should be developed through advertisement and the Internet, as well as within doctors' offices and through collaboration with patients' organizations. Patient information and consent forms should be made much simpler than those imposed within the framework of global studies because of FDA requirements. The French health system discourages the recruitment of patients by investigators who are not the family doctor or the usual care provider. Thus, motivation and education of general practitioners and hospital doctors may be increased by involving them during the trial design phase and in the publication process. Specific administrative solutions, within private or public institutions, need to be developed for investigators who do not personally wish to receive investigation fees. Because of lack of availability, investigators need to be assisted with study nurse services and site management organizations, particularly within hospitals and clinics, using the model of the Clinical Investigation Centres. Networks of clinical investigation centres and of individual investigators need to be created. Implementing these solutions should lead to better implications for and reputation of French clinical research.

"How much do you get paid if I volunteer?" Suggested institutional policy on reward, consent, and research.

Pharmaceutical companies often ask practicing physicians to conduct phase IV or postmarketing research on new drugs. Companies pay physicians to enroll their patients and report dosage and side-effect information. Postmarketing research embraces a multibillion dollar effort at promotion and familiarization, but subjects' informed consent to it normally does not include physician reward. Improving investigators' financial status while increasing medical risks to phase IV subjects is ethically unsound, especially if subjects are unaware of investigators' rewards. We suggest a model policy and guidelines that affirm subjects' need for informed consent, investigators' need for recognition and support, and institutions' need to protect patients from undisclosed risk and relations.