Improving transparency of regulatory data at EMA, Health Canada, FDA

Regulatory NewsRegulatory News | 29 October 2021 |  By 

Over the last decade, the European Medicines Agency (EMA), US Food and Drug Administration (FDA) and Health Canada (HC) have gotten better at disclosing previously confidential clinical data, a study published in The Journal of Law, Medicine & Ethics has found.  
However, each agency discloses this data in a variety of different ways, according to Alexander C. Egilman, with the Center for Outcomes Research and Evaluation at Yale–New Haven Hospital in New Haven, CT, and colleagues.
EMA’s Policy 0043 and Policy 0070 dictate how the agency can reactively and proactively disclose regulatory data for drugs and biologics. In Canada, HC’s Public Release of Clinical Information (PRCI) initiative, launched in 2019, goes further than EMA’s disclosure efforts “by proactively releasing data for not only approved, unapproved, and withdrawn drug and biologic submissions but also Class III and IV medical device applications,” Egilman and colleagues said. FDA, meanwhile, rarely proactively releases clinical data, having closed its pilot program to proactively publish clinical study reports (CSRs) in March of 2020. Instead, most information is obtained reactively from FDA through the Freedom of Information Act (FOIA).
In their study, Egilman and colleagues looked at what data were proactively and reactively disclosed by the three agencies. To assess proactive disclosures from EMA and HC, they compared the type of data released by each agency, which included the type of product, regulatory procedure, regulatory decision as well as pertinent dates and timing of regulatory decision and public releases. To evaluate how EMA, HC, and FDA handed reactive disclosures, the authors submitted information requests for Gilead’s hepatitis C antivirals sofosbuvir (Sovaldi) and ledipasvir/sofosbuvir (Harvoni) to each agency.
Proactive disclosures by EMA, HC
Data for 123 medical products (81 drugs, 38 biologics, 4 vaccines) and supporting data for 147 regulatory procedures (95 initial marketing authorization applications, 52 post-authorization applications) were proactively released by EMA between 2015 and 2021, while data from 73 medical products (45 drugs, 23 biologics, 3 vaccines, 2 medical devices) and supporting data for 75 regulatory procedures (62 initial marketing authorization applications, 13 post-authorization applications) were proactively released by HC from 2019 to April 2021.
During this period, Egilman and colleagues found FDA proactively released data from the marketing authorization application of one drug in 2018. The median time elapsed after an agency made the decision to proactively release data varied, with EMA taking 511 days, HC taking 150 days, and FDA 33 days.
In an interview with Focus, Egilman pointed to the Institute of Medicine’s 2015 report on sharing clinical trial data, which states agencies should strive to publish clinical trial data within 30 days for products granted regulatory approval.
“Given the widespread consensus on sharing clinical study reports and other summary level data, as well as the fact that two other major regulators, HC and EMA, have now been releasing these data proactively for years, I’m most surprised about FDA’s continued failure to make this important information available to the public,” he said.
Reactive disclosures by agencies
There have been few studies evaluating information requests to these agencies. Two papers published by Peter Doshi, of the Department of Pharmaceutical Health Services Research at the University of Maryland School of Pharmacy in Baltimore, found that EMA approved 66% of 457 information requests between 2010 and 2012, and took a median of 301 days to process information requests sent between 2011 and 2015.
For FDA, the agency granted 72% of requests in full or in part, and processed two-thirds of information requests in 61 days or more, Egilman and colleagues said in a previously published paper on FOIA requests sent to Department of Health and Human Services (HHS) agencies. Requests sent to HC were processed in a median of 132 days, they noted.
In their experience sending parallel information requests to EMA, HC and FDA for regulatory records and clinical data for Sovaldi and Harvoni, Egilman and colleagues found each agency took varying lengths of time to respond and released different information to the authors. The time from the initial request to when the agency released the data was 918 days for the FDA and 968 days for the EMA; HC took 155 days to release the data for Harvoni and 351 days for Sovaldi.
“I was surprised how long and resource intensive the process was to acquire clinical study reports [CSRs] and other data from the FDA,” Egilman told Focus. “It took over 2.5 years for FDA to produce the wide range of clinical data and regulatory records we requested, and the process involved multiple appeals and court filings.”
“By contrast, Health Canada, which we found to be the most efficient source of clinical study reports for older drugs, released the data packages, including CSRs, for Sovaldi and Harvoni in less than a year and it took less than 10 minutes for us to submit the information requests to HC,” he said.
The authors said FDA and HC “released substantially more regulatory data” compared with EMA. Released data from FDA and HC included “clinical overviews, summaries and integrated summaries of safety and efficacy, clinical study protocols and amendments, and narratives of deaths and serious adverse events.”
“It’s worth noting that information requests to FDA may be necessary to gain access to certain types of regulatory data, such as sponsor-regulator correspondence,” Egilman told Focus. “I was also surprised FDA released individual patient-level data, albeit heavily redacted, as I am unaware of a previous instance where they have released these data.”
Opportunities for improving transparency
Egilman noted each agency has an opportunity to improve transparency in its handling of clinical data involved in regulatory review. FDA, for example, can match HC and EMA by proactively publishing CSRs and other summary-level clinical data—but these actions should also include medical devices and unapproved or withdrawn products. Each agency should also seek to make policies that share individual patient data, he said.
Some agencies, such as EMA and FDA, also have citizenship requirements for requesting clinical data, which should be removed, Egilman explained. In addition, financial barriers to requesting information exist, such as through the United States’ FOIA. EMA and FDA can also improve by adopting a public online portal for posting requested clinical data, such as the one HC provides, Egilman said.
“I think the biggest obstacle to achieving increased transparency at FDA is agency inaction,” he said. “There needs to be greater political will both in the leadership at FDA and in the White House to push for greater clinical data transparency. The eroding public trust in FDA during the COVID-19 pandemic has further demonstrated the importance for FDA to enhance transparency of the clinical data of drugs, vaccines, and other medical products that it relies on to make decisions.”


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