British Medical Journalby Khaled El Emam, Tom Jefferson, Peter Doshi27 Aug, 15
In late 2010, the European Medicines Agency [EMA] became the first regulator in history to promulgate a freedom of information policy that covered the release of manufacturer submitted clinical trial data. Under a separate, new policy [policy 070], the EMA will take an additional step and create a web based platform for sharing manufacturers’ clinical study reports [CSRs] upon a decision being made on a marketing authorization application or its withdrawal.
CSRs contain significant details that are often missing in journal publications of the same trials—for example, details pertaining to patient relevant outcomes and adverse events—and are an important new tool for those engaged in research synthesis. While the policy anticipates that the agency will require individual participant data [IPD] to also be shared, the EMA has not yet committed to a final timeline for this.
But as the EMA works towards finalizing its guidance on the anonymization of CSRs, some companies and industry initiated guidance may be promoting practices that would diminish the value of the data the regulator ultimately distributes. For example, one recent industry guidance favors the redaction and removal of significant standard content in CSRs, ostensibly in an effort to have simple rules for anonymizing these documents. This includes the removal of patient narratives [for example, of serious adverse events and patient dropouts]; line listings [tables of individual level information about participants]; and the redaction of all patient demographics, dates of birth, and other items such as event or assessment dates.
Simple rules have the advantage of being easy to understand and do not require much sophistication to implement. Unfortunately, the major disadvantage is the resulting extensive information loss across the board. CSRs are already written without the use of directly identifying personal information, and maintaining as much of the original information in the CSRs is important to be able to perform accurate analysis—for example, to evaluate the risk of bias of trials.Thus far, the EMA’s draft guidance has erred towards less redaction of already partially anonymized CSRs, and away from blanket removal and redaction. It instead advocates a more nuanced risk analysis in compliance with recommendations from EU data protection authorities in order to maximize scientifically useful information in the CSR. The suggested approaches for further anonymization include selective masking/redaction, randomization, and generalization techniques…
Today, demand for data is an important driver of investments in clinical trial data sharing infrastructure, and it is debatable whether demand is growing as rapidly as some have expected or hoped. The GSK initiated ClinicalStudyDataRequest.com portal reports 104 valid requests [as of end of June 2015]; Project Data Sphere reports 900 authorized users; and the EMA, under its 2010 freedom of information based policy, has released over 2 million pages of regulatory documents. While this access has resulted in some publications and high profile research, such as the Cochrane review of neuraminidase inhibitors, one hopes for more…
For the moment, there’s no infrastructure or funding support for such enterprises, and it’s certainly a lot of work. We were on our own. But it was plenty rewarding and well worth the effort. It’s the perfect kind of project for graduate students and junior faculty who need a challenge that will flex a wide range of analytic skills with a definable output. I’m sure I’ve learned as much doing this as back during my jurassic age in an NIH fellowship. I can even imagine "watch-dogging" unpublished or questionable studies and reevaluating them as coming into the domain of some group like the Cochrane Collaboration or a similarly structured independent academy.
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USEICH HARMONISED TRIPARTITE GUIDELINESTRUCTURE AND CONTENT OF CLINICAL STUDY REPORTS – E330 November 1995