WHO and medicines regulators call for more drug and vaccine transparency

Pharma companies should make detailed data for all new medicines and vaccines public, the World Health Organisation and a global coalition of regulatory agencies said today.

According to a joint statement they published today:

“ICMRA and WHO call on the pharmaceutical industry to provide wide access to clinical data for all new medicines and vaccines (whether full or conditional approval, under emergency use, or rejected). Clinical trial reports should be published without redaction of confidential information for reasons of overriding public health interest.”

WHY IS THIS IMPORTANT?

The statement refers to Clinical Study Reports (CSRs), which are extensive documents produced by pharma companies that describe the conduct and outcomes of clinical trials. Medicines regulators worldwide review CSRs to assess whether new medicines are safe and effective before allowing them onto the market.

However, most regulators then lock CSRs away in their archives and refuse to allow independent researchers to access them, citing concerns about commercial or patient confidentiality. Currently the only exceptions to this rule are the European Medicines Agency and Health Canada. The U.S. Food and Drug Administration refuses to grant access to CSRs, as do some national medicines regulators within the European Union.

In addition, some pharma companies already grant researchers access to CSRs as part of their voluntary transparency commitments.

A recent study showed that CSRs include information on the harms of drugs that often remains hidden in publicly available information sources such as journal articles and trial registries.

WHAT ARE THE IMPLICATIONS?

Today’s statement may mark a new approach to CSR disclosure by regulators.

The International Coalition of Medicines Regulatory Authorities (ICMRA), which co-signed the statement, includes numerous regulatory agencies that so far have refused to release even redacted CSRs, including the U.S. Food and Drug Administration. However, the FDA immediately dampened expectations for rapid change (see FDA statement further below).

REVISITING COMMERCIAL CONFIDENTIALITY

The statement is likely to set alarm bells ringing within the pharma industry, which has long argued – including in front of court – that the disclosure of some information contained in CSRs is likely to give competitors an unfair advantage. The statement indicates that WHO does not appear to share this view, arguing that “both positive and negative clinically relevant data should be made available, while only personal data and individual patient data should be redacted.”

Both the European Medicines Agency and Health Canada currently only release CSRs after commercially confidential information has been redacted; typically such redactions are very limited in scope.

WHO CRITICISES PUBLIC AND PHILANTHROPIC RESEARCH FUNDERS

The statement takes a pointed swipe at medical research funders. It laments that “not all past efforts [to improve transparency] have been successful. Often this was because they were unsustainable due to reliance on goodwill or lack of appropriate resourcing.”

The statement references the 2017 WHO Joint Statement, in which major public and philanthropic funders worldwide committed to ensuring that all clinical trials are registered and reported. A key commitment that funders made in the statement was to audit compliance by their grantees. To date, as far as TranspariMED is aware, only three signatories – NIHR, MRC and the Wellcome Trust – have made such audit reports public. Four years after signing up, the Melinda and Bill Gates Foundation, the Indian Council of Medical Research, Inserm, and the Research Council of Norway, have yet to deliver of their promises.

FIRST REACTIONS TO THE STATEMENT

In first reactions, transparency experts welcomed the statement.

Jorg Schaaber from the German BUKO Pharma-Kampagne said:

“Finally, the club of major drug regulators have taken up the call for transparency for medical research and promise to publish the complete clinical trial results at the time of licensing or rejecting a new drug. This step is long overdue and a success for many scientists, public interest groups and campaigners who have demanded open access to data since many years.”

Commenting in Twitter thread, Matthew Herder, Director of the Health Law Institute, described the statement as “significant” but added that:

“Even in jurisdictions where the is ample legal authority to disclose clinical study reports and other data that bear upon a drug/vaccine's safety + efficacy, it appears transparency continues to be a source of negotiation and thus drain on regulatory resources.”

“While the statement is important, it strikes me that regulators too could use their powers to expand the transparency + do away with unnecessary negotiations which inevitably lead to delays.”

Consilium Scientific, a UK-based nonprofit founded by former NICE head of scientific advice Leeza Osipenko, posted a Twitter tutorial noting that:

"This is a rhetorical, albeit important and needed, discourse. The statement is unlikely to be backed by action, it carries no legislative weight, there are no resources or appetite to enforce it at any level."

"Regulators have been reluctant to act despite publicly supporting the ethical measures, transparency and interests of patients on paper."

"Resource burden is an issue and a very convenient excuse just not to do anything until asked and then to decide whether to fulfil the request directly. Data might be released to a specific person/company/institution but it does not end up in the public domain."

"We need to create a system where it is unthinkable that clinical data are not in the public domain but we live in the system where it is unthinkable to have transparency when corporate and academic interest are at stake."

Natalie Rhodes, policy officer with the health arm of Transparancy International, the global anticorruption organisation, said:

"We echo the joint statement by the WHO and ICMRA calling for the sharing of clinical trial reports without redactions. This is particularly important in the context of Covid vaccines, in the interest of transparency and public health. All countries must follow the lead of the European Union and Canada on this, and irrespective of national policies the pharmaceutical industry must provide access. This is a crucial step for the safe and effective development of not just Covid-19 vaccines but all medical technology. There need to be stronger governance mechanisms in place to ensure that public health is always the first priority."

An FDA spokesman told STAT News that:

“[T]he FDA understands the joint statement issued by ICMRA and WHO to be strategic and aspirational and not a statement of policy. The agency’s actions are governed by U.S. law, driven by our mission to protect the public health, and articulated through agency rulemaking and the issuance of FDA guidance to industry.”

The European Medicines Agency struck a more positive note. Emer Cooke, EMA’s Executive Director who also chairs ICMRA, said:

“As our policy of proactive publication of clinical data demonstrates, EMA has long been committed to making the data on which our regulatory decision-making is based available for public scrutiny. I’m very pleased that ICMRA and WHO have come together on this and are supporting our own efforts and similar approaches. This could be the beginning of a new era of much wider access to trial results data for the benefit of public health.”

Global pharma lobby group IFPMA released a statement "recognising" the call. It noted that:

"[The] biopharmaceutical industry is fully committed to enhancing public health through responsible sharing of clinical trial data in a manner that ensures safeguarding the privacy of patients, clinical investigators and trial participants; respecting the integrity of national regulatory systems; and maintaining incentives for investment in biomedical research."

Germany's IQWiG, which assesses the efficiacy and safety of new drugs and medical devices, commented that:

"Comprehensive information on all clinical trials, including all results, must be publicly available - IQWiG has been advocating this for many years."

WHO SIGNED UP TO THIS?

The following regulators are members of ICMRA:

Full members

• Australia: Therapeutic Goods Administration (TGA)

• Brazil: National Health Surveillance Agency (ANVISA)

• Canada: Health Products and Food Branch Health Canada (HPFB-HC)

• China: National Medical Products Administration (NMPA)

• European Union: European Commission Directorate-General for Health and Food Safety (DG SANTE)

• European Union: European Medicines Agency (EMA)

• France: National Agency for the Safety of Medicines and Health Products (ANSM)

• Germany: Paul-Ehrlich-Institut (PEI)

• Mexico: Federal Commission for Protection against Health Risks (COFEPRIS)

• India: Ministry of Health and Family Welfare (MoHFW)

• Ireland: Health Products Regulatory Authority (HPRA)

• Italy: Italian Medicines Agency (AIFA)

• Japan: Ministry of Health, Labour and Welfare (MHLW)

• Japan: Pharmaceuticals and Medical Devices Agency (PMDA)

• Republic of Korea: Ministry of Food and Drug Safety (MFDS)

• The Netherlands: Medicines Evaluation Board (CBG-MEB)

• New Zealand: New Zealand Medicines and Medical Devices Safety Authority (Medsafe)

• Nigeria: National Agency for Food and Drug Administration and Control (NAFDAC)

• Singapore: Health Sciences Authority, Singapore (HSA)

• South Africa: South African Health Products Regulatory Authority (SAHPRA)

• Sweden: Swedish Medicines Products Agency (MPA)

• Switzerland: Swissmedic

• UK: Medicines & Healthcare products Regulatory Agency (MHRA)

• US: Food and Drug Administration (FDA)

Associate members

• Argentina: National Administration of Drugs, Foods and Medical Devices (ANMAT)

• Austria: Austrian Medicines and Medical Devices Agency (AGES)

• Colombia: National Food and Drug Surveillance Institute (INVIMA)

• Cuba: Center for State Control of Medicines, Equipment and Medical Devices (CECMED)

• Denmark: Danish Medicines Agency (DKMA)

• Israel: Ministry of Health (MOH)

• Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (URPL)

• Portugal: National Authority of Medicines and Health Products (INFARMED)

• Russia: Federal Service for Surveillance in Healthcare (Roszdravnadzor)

• Saudi Arabia: Saudi Food & Drug Authority (SFDA)

• Spain: Spanish Agency of Medicines and Medical Devices (AEMPS)

TranspariMED has contacted the World Health Organisation for comment, and will update this blog with WHO’s response next week.

Today’s joint statement by WHO and ICMRA can be accessed here.

TranspariMED’s website contains an overview of what CSRs are and why they are so important with links to relevant research, and an annotated bibliography on access to CSRs.