U.S. diplomats pressure European regulators to curb clinical trial transparency

A recent report by the Office of the United States Trade Representative reveals that U.S. diplomats are working behind the scenes to curb moves towards greater clinical trial transparency in Europe.

According to the latest National Trade Estimate Report on Foreign Trade Barriers:

“[C]hanges to European Medicines Agency (EMA) policy regarding disclosures of clinical trial data, including potential disclosure of confidential commercial information submitted to EMA by pharmaceutical firms seeking marketing authorization, are also of concern to stakeholders. The United States continues to engage with the EU and individual Member States on these matters.”

The passage presumably refers to EMA’s policy of proactively releasing Clinical Study Reports (CSRs), lengthy documents that provide extremely detailed information on clinical trials of new medicines. For example, a 2021study found that CSRs contained unique data on patient deaths caused by cancer drugs.

Reactions by experts and industry

Expert reaction. Beate Wieseler, who heads the department of drug assessment at the Institute for Quality and Efficiency in Health Care, or IQWiG, an independent German agency that assesses the effectiveness of medicines, told STAT News that:

“High quality, evidence-based health care is only possible, if all methods and results of all trials with drugs in current use are publicly available.”

.

“Therefore, complete information on clinical trials needs to be published at the point of marketing authorization at the latest. These data are needed for decision making at the health care system level, for clinical guidelines and for individual treatment decisions.

"It is unclear to me how withholding clinical trial data from patients, physicians and the general public can be considered appropriate.”

Industry reaction. A spokesperson for the American pharma lobby group PhRMA told the same publication that:

"[Pharma companies are] committed to enhancing public health through responsible sharing of clinical trial data in a manner that safeguards the privacy of patients, respects the integrity of national regulatory systems and maintains incentives for investment in biomedical research."

"PhRMA and its members commend the U.S. Trade representative for continuing to engage with the European Union and individual member states to ensure that any sharing of clinical trial data by the EMA reflects these essential principles.”

Wrong target?

The only Clinical Study Reports released by EMA in recent years have been related to Covid drugs and vaccines, raising the question of what exactly U.S. diplomats are pushing back against.

According to Transparency International and Cochrane:

“Making full trial reports – including but not limited to CSRs – publicly accessible reduces the potential for mistakes, misinterpretations, bias, evidence distortion, corruption or fraud in other forms of trial reporting. In addition, access to full trial reports can help independent experts flag benefits or harms that the original team conducting the trial may have overlooked or incompletely reported, thus improving patient safety and speeding up the discovery of new treatments and cures.”

“Regulators worldwide… should make all CSRs (including all appendices) currently held in their archives publicly accessible after making limited redactions to safeguard commercial and patient confidentiality. Going forward, regulators should make newly received CSRs publicly accessible at the time of regulatory approval, or within 24 months latest of receiving the CSR if not approved.”

EMA’s wider disclosure programme was ‘temporarily’ put on hold in 2018. EMA has still not announced when it will be resumed. It is unclear whether U.S. pressure has dissuaded EMA from restarting the programme.

European courts have ruled that Clinical Study Reports do not constitute confidential commercial information per se. Any potentially sensitive information is redacted from the documents before EMA releases them under Policy 0070. In practice, such redactions have been minimal in scope.

Access to Clinical Study reports by country

The approach to releasing Clinical Study Reports held by national medicines regulators within individual European countries varies widely. National regulators in Germany and Finland have in the past refused to release such documents to independent researchers. In contrast, regulators in Denmark, Sweden and the Netherlands have been more transparent.

Canada currently sets the gold standard for transparency in this area, routinely posting (minimally redacted) Clinical Study Reports online.

Japan does not normally proactively release Clinical Study Reports, but a 2021 study noted that the “Japanese Pharmaceuticals and Medical Devices Agency… released thousands of pages from company submissions for COVID-19 vaccines.”

A few years ago, the U.S. Food and Drug Administration ran a pilot of releasing Clinical Study Reports that were voluntarily made available by pharma companies. The pilot was discontinued after only one report had been disclosed.

For more information on access to Clinical Study Reports, see the 2018 annotated bibliography "Access to Clinical Study Reports: mechanisms, barriers and benefits".

For a more detailed analysis of the 2022 Office of the United States Trade Representative (USTR) report, including an analysis of U.S. pushbacks against pharmaceutical pricing and reimbursement policies in Europe, please see this blog by Knowledge Ecology International (KEI) Europe.