European regulators back access to raw trial data -- with caveats
“It is ‘neither desirable nor realistic to maintain the status quo’ of clinical trial data being available on a limited basis, a group of leading European drug regulators believes. The officials from the European Medicines Agency (EMA), France’s Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and the Dutch Medicines Evaluation Board (CBG-MEB) have pitched into the debate over selective publication of clinical-trial data in an article for the open-access journal PloS Medicine. They were responding to a piece in PloS Medicine by Peter Doshi and colleagues about the difficulty of securing access to reliable clinical-trial data on Roche’s antiviral Tamiflu (osteltamivir). Doshi et al argued that full clinical trial reports on licensed drugs should be made publicly available to enable independent re-analysis of these products’ risks and benefits. The regulators agree with Doshi et al. that clinical trial data should not be regarded as commercial confidential information. Most patients who enrol in clinical trials do so with the assumption that they are contributing to medical knowledge, they observe. Non-disclosure of comprehensive trial results undermines that philanthropic sentiment... By clinical trials results, Rasi et al. mean ‘not just the protocol, summary tables, and figures of (mostly) randomised controlled trials (RCTs), but the full ‘raw’ data set, including data at the patient level’... Other, ‘potentially more important’ benefits that could arise from public disclosure of raw trial data include developing predictive models for patient selection to appropriate treatments; and, eventually, ‘machine learning systems that will allow clinicians to match a patient’s electronic health record directly to RCT and observational study datasets for better, individualised therapeutic decisions’, the regulators suggest... There is a ‘small risk’ that personal data could inadvertently be publicised or that individual patients could be identified from anonymised datasets, Rasi et al acknowledge – for example, in the case of clinical trials for ultra-rare diseases. ‘Achieving an adequate standard of personal data protection is not an insurmountable obstacle, though, and proposals for best practice for publishing raw data are available,’ they add. Nonetheless, ‘implementation is not straightforward, standards will need to be agreed upon up front, and data redaction may in a few cases be resource intensive’. A second and ‘likely more contentious’ caveat is the implied assumption in the debate over sponsor-independent analyses of clinical trial data that these analyses are necessarily free from conflicts of interest (CoIs). ‘We beg to differ,’ the authors comment. ‘Personal advancement in academia, confirmation of previously defended positions, or simply raising one's own visibility within the scientific community may be powerful motivators.’ Analyses by sponsor-independent scientists ‘are not generated in a CoI-free zone and, more often than not, ego trumps money’, Rasi et al. suggest. As such, the regulators are ‘concerned that unrestricted availability of full datasets may in some cases facilitate the publication of papers containing misleading results, which in turn lead to urgent calls for regulatory action’. In the worst case, this would ‘give rise to unfounded health scares with negative public health consequences such as patients refusing vaccinations or discontinuing drug treatment’, they warn. Nor is independent analysis per se a guarantee of high quality... Rasi et al. purpose a three-pronged approach to resolve these potential conflicts:  Developing and agreeing on adequate standards for the protection of personal data when publicizing RCT datasets...  Ensuring the general adoption of established quality standards for meta-analyses and other types of (confirmatory) data re-analysis that may warrant regulatory action...  Establishing ‘rules of engagement’. For example, the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance has recently published guidance for raw data-sharing in the field of observational studies based on healthcare databases."