An analysis of marketing authorisation applications via the mutual recognition and decentralised procedures in Europe.

PURPOSE: The aim of this study is to provide a comprehensive overview of the outcomes of marketing authorisation applications via the mutual recognition and decentralised procedures (MRP/DCP) and assess determinants of licensing failure during CMDh referral procedures. METHODS: All MRP/DCP procedures to the Co-ordination group for Mutual recognition and Decentralised procedures-human (CMDh) during the period from January 2006 to December 2013 were analysed. Reasons for starting referral procedures were scored. In addition, a survey under pharmaceutical companies was performed to estimate the frequency of licensing failure prior to CMDh referrals. RESULTS: During the study period, 10392 MRP/DCP procedures were finalized. Three hundred seventy-seven (3.6%) resulted in a referral procedure, of which 70 (19%) resulted in licensing failure, defined as refusal or withdrawal of the application. The frequency of CMDh referrals decreased from 14.5% in 2006 to 1.6% in 2013. Of all referrals, 272 (72%) were resolved through consensus within the CMDh, the remaining 105 (28%) were resolved at the level of the CHMP. Most referrals were started because of objections raised about the clinical development program. Study design issues and objections about the demonstration of equivalence were most likely to result in licensing failure. An estimated 11% of all MRP/DCP procedures resulted in licensing failure prior to CMDh referral. CONCLUSION: Whereas the absolute number of MRP/DCP procedures resulting in a referral has reduced substantially over the past years, no specific time trend could be observed regarding the frequency of referrals resulting in licensing failure. Increased knowledge at the level of companies and regulators has reduced the frequency of late-stage failure of marketing applications via the MRP/DCP.

Research monitoring by US medical institutions to protect human subjects: compliance or quality improvement?

In recent years, to protect the rights and welfare of human subjects, institutions in the USA have begun to set up programmes to monitor ongoing medical research. These programmes provide routine, onsite oversight, and thus go beyond existing oversight such as investigating suspected misconduct or reviewing paperwork provided by investigators. However, because of a lack of guidelines and evidence, institutions have had little guidance in setting up their programmes. To help institutions make the right choices, we used interviews and document analysis to study how and why 11 US institutions have set up their monitoring programmes. Although these programmes varied considerably, we were able to distinguish two general types. 'Compliance' programmes on the one hand were part of the institutional review board office and set up to ensure compliance with regulations. Investigators' participation was mandatory. Monitors focused on documentation. Investigators could be disciplined, and could be obliged to take corrective actions. 'Quality-improvement' programmes on the other hand were part of a separate office. Investigators requested to be monitored. Monitors focused more on actual research conduct. Investigators and other parties received feedback on how to improve the research process. Although both types of programmes have their drawbacks and advantages, we argue that if institutions want to set up monitoring programmes, quality improvement is the better choice: it can help foster an atmosphere of trust between investigators and the institutional review board, and can help raise the standards for the protection of human subjects.

Ethical review from the inside: repertoires of evaluation in Research Ethics Committee meetings.

Evaluating the practice of ethical review by Research Ethics Committees (REC) could help protect the interests of human participants and promote scientific progress. To facilitate such evaluations, we conducted an ethnographic study of how an REC reviews research proposals during its meetings. We observed 13 meetings of a Dutch REC and studied REC documents. We coded this material inductively and categorised these codes in two repertoires of evaluation: a repertoire of rules and a repertoire of production. In the repertoire of rules the REC applies rules, weighs scientific value and burdens to the participants and makes a final judgment on a research proposal in a meeting. In the repertoire of production, REC members check documents and forms and advise researchers on how to improve their proposals and can use informal communication. Based on these findings, we think that evaluations of the practice of ethical review should take into account the fact that RECs can use a repertoire of rules and a repertoire of production to evaluate research proposals. Combining these two repertoires can be a viable option so that the REC gives researchers advice on how to improve their proposals to prevent rejection of valuable research.

[Preventing fainting due to needles or blood]. / Het voorkómen van flauwvallen door naalden of bloed.

A 29-year-old medical student suffered from vasovagal syncope triggered by blood and blood-related procedures, such as injections and injuries. Fainting was preceded by prodromal symptoms like light-headedness and altered vision. The patient consulted the Syncope Unit at the Academic Medical Centre, Amsterdam, the Netherlands, and received instructions on how to apply counterpressure manoeuvres. He was also successfully treated with psychological deconditioning, which consisted of desensitisation through exposure in vivo and cognitive behavioural therapy. Emotionally triggered vasovagal syncope is predominantly seen in young people and can lead to serious complications. It can be treated with simple interventions like drinking water and performing counterpressure manoeuvres. Psychological deconditioning is an effective additional therapy.

Two prognostic indicators of the publication rate of clinical studies were available during ethical review.

OBJECTIVE: To identify prognostic indicators of the publication rate of clinical studies, available to research ethics committees (RECs) during review. STUDY DESIGN AND SETTING: Retrospective survival study of a random sample of 100 studies, approved by a Dutch academic REC, with follow-up information by questionnaire and bibliographic searches. Multivariate Cox regression analysis of the association between publication rate and seven factors available during review: six study characteristics and the number of letters sent by the committee during review representing the length of the review process. RESULTS: Two factors were associated with publication rate: studies with possible therapeutic benefit to participants were less likely to be published than nontherapeutic studies (adjusted hazard ratio [AHR]: 0.16; 95% confidence interval [CI]: 0.03-0.54); with every letter sent, publication was less likely (AHR: 0.46 per letter; 95% CI: 0.17-0.98). Possibly, studies with more-than-minimal burdens to participants were more likely to be published than studies with minimal burdens (AHR: 3.90, 95% CI: 1.03-16.64). CONCLUSION: We identified two prognostic indicators of publication rate. After suitable replication, RECs might explore using prognostic indicators, such as these, to target study protocols at high risk for nonpublication. Discussing the risk of nonpublication with investigators could help prevent nonpublication.