By Sara Gambrill, contributing Editor
(This is a continuation of Sara's review of her time at the 2011 Post Aprroval Summit in Boston)
On a panel, regulators from Europe and Canada as well as representatives from industry operating in the U.S. and Europe and U.S. academia all described an array of activities and safety initiatives by their respective governments to improve the utility of findings from post-market research and/or communicating them to patients.
Richard Platt, M.D., a professor of Medicine at Harvard Medical School described the Mini-Sentinel initiative, an initiative within the Sentinel Initiative, which is undertaking the development of the Sentinel System—a national electronic safety monitoring system in the U.S. The goal of Mini-Sentinel, a pilot project, is active surveillance so that FDA can start to develop as quickly as possible an evidence-based understanding of what the safety profile of a drug is. Platt stated that the Mini-Sentinel would be considered successful if it discovers a previously unsuspected adverse reaction. A few programs will begin soon, including one that implements an active surveillance protocol for acute myocardial infarction related to new oral hypoglycemics. Mini-Sentinel will also evaluate safety issues for older drugs and the impact of regulatory actions, e.g., restricted distribution. Mini-Sentinel will also conduct active surveillance of specific outcomes following rotavirus and HPV vaccines. A Mini-Sentinel Portal at www.minisentinel.org is almost ready for release.
The challenges with the Sentinel System will be the need for timeliness in detection of signals and follow-up, avoiding false alarms, and the need for increased human resources when there are work surges. Platt was also quick to point out that the Sentinel System is only for drugs, not devices, and speakers representing industry and government earlier in the day bemoaned the dearth of post-market data for medical devices and shared some of the ways to increase knowledge in this area.
Nancy Dreyer, MPH, Ph.D., chief of scientific affairs and SVP, Outcome, described the PROTECT Project, a public-private partnership to create new methodologies in pharmacovigilance and pharmacoepidemiology, funded by the Innovative Medicine Initiative (IMI), a 2-billion euro public-private initiative funded in equal parts by the European Commission (EC) and the European Federation of Pharmaceutical Industries and Associations (EFPIA). IMI’s overall goal is to remove the major bottlenecks in drug development where research is key. PROTECT’s goal is to enhance early detection and assessment of adverse drug reactions from various data sources, e.g., clinical trials, spontaneous reporting and observational studies. It is also to enable the integration and presentation of data on benefits and risks. Methods will be tested in real-life situations.
Stella Blackburn, MA, MSc, risk management development and scientific lead, European Medicines Agency (EMA) had earlier discussed new pharmacovigilance legislation, 1235/10 updating 726/2004, that went into effect in the EU at the end of last year and its impact on the risk management plan (RMP). She also discussed the new policies and procedures that 2010/84/EC introduced as well as the new Pharmacovigilance Risk Assessment Committee (PRAC). RMPs are required for all new approvals by EMA now, but they present some challenges, i.e., the definition of an RMP itself, which may be too defining in that it only describes risks but not benefits. Better communication of the risk with the added context of the benefit as well as real-world efficacy has been proposed. The RMP also has some EU-specific areas that might be better handled with a more modular RMP with seven parts.
On the panel, Blackburn updated everyone on the activities and initiatives of an EMA work project, the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP), which brings together expertise from 87 partner organizations in pharmacoepidemiology and pharmacovigilance across Europe. ENCePP’s goal is to strengthen the post-authorization monitoring of medicinal products in Europe by facilitating the conduct of independent multi-center, post-authorization studies focusing on safety and benefit-risk. Another goal is to burnish the image of clinical trials and to provide transparency. ENCePP study results are never confidential. Requirements are that lead investigators must be from one of the ENCePP partners and follow the ENCePP Code of Conduct. Prior registration of the study in the e-Registry of Studies, developed in May 2010 and live in November, is also required to increase transparency, reduce publication bias and promote information exchange. The purpose of the research must be scientific and not promotional. Studies should not be designed to achieve a particular result. Must register study in ENCePP database prior to study start.
Diane Forbes, associate director of Canada’s Drug Safety and Effectiveness Network (DSEN), described the expectations, objectives and activities of the DSEN in post-market research. The Canadian Institutes of Health Research (CIHR) and Health Canada are partnering to establish the DSEN, which comprises three collaborating centers representing a national network of researchers. DSEN is being established as an independent source of real-world drug safety and effectiveness information to inform regulators, policy makers, healthcare providers and patients. In addition, particular emphasis will be put on gathering this information on special and vulnerable populations such as children and pregnant women.
When the panel was asked if they collaborated with each other on any of these safety initiatives, the answer was that some of them had exchanged telephone calls about their respective programs. The initiatives are clearly single-country efforts, with the exception of EU initiatives that cover 27 countries. With the extraordinary effort it takes to get one of these programs up and running, it would seem almost impossible to coordinate a global effort at this time, but as research is collected, perhaps regulators will have opportunities to learn from each other. Canada seemed to have the steepest learning curve, as it was clearly taking its cues from other countries and its regulatory system is still evolving.