Applied Clinical Trials
With the push for the earliest possible release of clinical study reports for COVID-19 treatments, European regulators and reimbursement agencies might experience a heightened vulnerability, as public expectation about coronavirus cures rises.
The Institute for Quality and Efficiency in Healthcare (IQWiG) is pushing for the earliest feasible release of clinical study reports for authorized treatments and vaccines for COVID-19, in a bid to open up research in the field. Dr. Beate Wieseler and Dr. Thomas Kaiser, the heads of drug assessment at IQWiG, have written to Professor Guido Rasi, the executive director of the European Medicines Agency (EMA), urging the publication of all case safety reports (CSRs) on all COVID-19 medicines and vaccines on the day of marketing authorization.
It seems a simple enough request, because it does little more than, in effect, restate what is already provided for in EU legislation. But it may say something too about a certain sense of vulnerability that regulators and reimbursement agencies might experience as public expectation about coronavirus cures rises, and they find their gateway role acquires a consequently-heightened profile.
The IQWiG officials take a longer look at the pandemic challenges than just a simple race to get the first products into play to tackle the novel coronavirus. They want results brought quickly into the public domain as a guide to other researchers still working on other approaches and treatments. Indirectly invoking their position among the key sentinels guarding access to German healthcare funding for medicines, they also indicate that there are hard choices that will have to be made over who pays for what. In what looks like a bid to avoid general exuberance and enthusiasm overwhelming good sense in the heat of the moment, they say everything possible should be done as soon as possible to contribute to the best responses in allocating resources to reimbursement. “EMA should support the international research community by publishing clinical study reports on medicine and vaccine trials at the time of marketing authorization and to inform treatment decisions.”
Describing COVID-19 pandemic as “the greatest healthcare and economic crisis Europe and many other parts of the world have faced in several decades,” IQWiG officials depict the entire research and regulatory community as feeling their way in uncharted territory. “Unprecedented research efforts are underway to develop or identify effective medicines and vaccines. Researchers from all over the world have joined forces to identify or develop, test, and evaluate medicines and vaccines to fight the pandemic,” they said.
At the end of this pipeline, “regulatory agencies will have a crucial role in deciding which of these medicines and vaccines will be made available to patients and the public”. And Weiseler and Kaiser are acutely aware of the pressures that regulators are under in the face of a rising death toll, soaring infection and morbidity, and the wide-ranging economic and social consequences of extensive lock-downs.
“Because of the severity of the current situation, regulators are aiming to accelerate the marketing authorization process,” IQWiG comments, noting that first treatments have already been evaluated by regulators, as recently seen with the fast emergency use authorization of the antiviral remdesivir by the FDA, and that EMA has also started a “rolling review” of remdesivir.
This acceleration effort is understandable, IQWiG says, “and to be welcomed in this exceptional situation.” But officials add-pointedly-“to achieve sustainable effects in healthcare, this effort must also include the publication of CSRs to make the full information on any new medicine or vaccine publicly available as soon as possible.”
The international research community is already undertaking coordinated efforts-IQWiG cites the living mapping and living systematic review of COVID-19 studies-to compile all emerging information on medicines and vaccines for the virus, it says, with a view to ensuring the optimal planning and conduct of research.
“To assess these products further and to accelerate the development of additional products, the fast and full public availability of the information submitted to regulators is of utmost importance,” say Weiseler and Kaiser-and in support of the regulatory decision-making process, those “detailed and well-organized evidence packages, CSRs,” will play an important role.
Recalling some of EMA’s initiatives in releasing data to the public, and its legal battles with companies opposed to the release of data in CSRs, IQWiG officials make an appeal to the agency’s reputation as a champion of transparency: “In recent years, EMA has been a pioneer of data transparency among regulatory agencies. EMA’s policies on access to documents and proactive publication of CSRs have made extensive clinical trial information publicly available. EMA has defended this transparency before the Court of Justice of the European Union. It is exactly this transparency that is currently needed.”
IQWiG recruits another element to their appeal: “Transparency is also vital to maintain public trust during the crisis,” it says, doubtless conscious of the oceans of false information-and consequent public skepticism-threatening to overwhelm regulatory processes. “With its established processes, EMA is in a unique position to make a difference in the worldwide fight against the pandemic,” officials conclude.
The letter, on an IQWiG letterhead, is co-signed by several other conspicuous figures who are not officials of the Germany agency. They include Prof. Dr. Isabelle Boutron of the clinical epidemiology center at Inserm and the University of Paris, who is also director of Cochrane France; Prof. Dr. Declan Devane of the College of Medicine, Nursing and Health Sciences at the National University of Ireland in Galway, who is also director of Cochrane Ireland; Prof. Dr. Gerald Gartlehner of the Department for Evidence-based Medicine and Evaluation at the Danube University at Krems, who is also director of Cochrane Austria; Prof. Dr. Jörg Meerpohl of the Institute for Evidence in Medicine at the University of Freiburg, who is also director of Cochrane Germany; and Prof. Dr. Philippe Ravaud, also of the clinical epidemiology centre at Inserm and the University of Paris, who is also the chair of the Cochrane scientific committee.
This co-signed letter says something else about the IQWiG initiative. Gartlehner is the only one of the additional names who has any direct and public association with IQWiQ: his many roles also include being the chair of its advisory board. But the prominence of Cochrane dignitaries is a clear indication of how seriously IQWiG views the risks of public pressure distorting or disrupting the rigor of regulatory processes.
The Cochrane network is well-known and respected for its insistence on impartial assessment of evidence in health decision-making, and has become a byword in Europe for opposition to what it has often depicted as undue secrecy, particularly within the pharmaceutical industry. It is not too fanciful to speculate that IQWiG, itself well-known for its caution in drug assessment, may have felt that in the heat of the current crisis, it needed to pull in all the allies it could for maintaining a strict line in its own decision-making.
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium