The organisations supposedly overseeing the authorisation of new medicines are not sufficiently independent from the companies they are meant to regulate, according to a new investigation by The BMJ that asks the question: From FDA to MHRA: are drug regulators for hire?
"Industry money saturates the globe's leading regulators", said Dr Maryanne Demasi PhD, an investigative journalist from Australia, in the light of her research into the funding of six national drugs regulators from across the globe, including the UK, Europe, Australia, Canada, Japan, and the US.
Dr Demasi, whose work is focused on "holding governments and public health authorities to account", raised significant questions about the influence funding has on regulatory decisions.
Following a long series of drug and device scandals, drug regulators worldwide have increasingly prompted the question quis custodiet ipsos custodes? - who guards the guards themselves?
Patients and doctors expect regulators to provide an unbiased, rigorous assessment of new medicines before they hit the market. But over the past decades, regulatory agencies have seen increasingly large proportions of their budgets funded by the industry they are supposed to regulate, Dr Demasi pointed out.
For the investigation, The BMJ asked regulators a series of questions about their funding, transparency of decision-making and data, and the rate at which new drugs are approved. Where agencies regulate beyond medical products (for example, food), such as those of the US and Canada, it assessed the proportion of the human drugs budget derived from industry.
Majority of Regulators' Budgets Derive From the Industry They're Regulating
It found:
- In the UK, 86% of the Medicines and Healthcare products Regulatory Agency (MHRA)'s budget is derived from the drug industry
- Industry fees now fund 89% of the European Medicines Agency (EMA), up from 20% in 1995
- In the US, the proportion of the Food and Drug Administration (FDA)'s human drugs budget derived from industry fees has increased 30-fold since a 1992 Act that allowed direct industry funding as "user fees" to support the cost of swiftly reviewing drug applications, up from around $29 m in 1993 to $884 m (65%) in 2016
- In Australia, 96% of the Therapeutic Goods Administration's fees came from industry, the highest proportion of all those in the investigation
- Regulator Health Canada had the lowest proportion of its drugs budget from industry fees, at 50.5%
- In Japan, regulator Pharmaceuticals and Medical Devices Agency received 85% of its budget from the industry
The paper pointed out that in 2005, the House of Commons' Health Committee evaluated the influence of the drug industry on health policy, including on the MHRA. The Committee was concerned that industry funding could lead the agency to "lose sight of the need to protect and promote public health above all else, as it seeks to win fee income from the companies".
Yet, "nearly two decades on, little has changed." The phenomenon is global; "industry funding of drug regulators has become the international norm."
Other than Japan, which did not disclose an answer, the proportions of positive decisions for drug company applications for new medicines approvals in 2020-2021 were:
- UK 98.5%
- Europe 88%
- USA 69% of decisions by the FDA Center for Drug Evaluation and Research; 29% of decisions by the FDA Center for Biologics Evaluation and Research
- Australia 94%
- Canada 83%
Funding Influences Regulatory Decisions
"For decades, academics have raised questions about the influence funding has on regulatory decisions, especially in the wake of a string of drug and device scandals, including opioids, Alzheimer's drugs, influenza antivirals, pelvic mesh, joint prostheses, breast and contraceptive implants, cardiac stents, and pacemakers," Dr Demasi said.
Analysis in the US, where before the 1992 Act the FDA was a fully taxpayer-funded entity, has shown that "reliance on industry fees is contributing to a decline in evidentiary standards, ultimately harming patients". The same is true of individuals; FDA Advisory Committee members with financial interests in the sponsoring firm have been shown to be more likely to vote in favour of the sponsor's product.
Donald Light, professor of comparative health at Rowan University in New Jersey, US, and an expert on drug regulation, commented in The BMJ: "Being largely funded by fees from the companies whose products it is charged to evaluate is a fundamental conflict of interest and a prime example of institutional corruption.
"It’s the opposite of having a trustworthy organisation independently and rigorously assessing medicines. They're not rigorous, they're not independent; they are selective, and they withhold data. Doctors and patients must appreciate how deeply and extensively drug regulators can't be trusted so long as they are captured by industry funding."
Independent Advisors Aren't Independent Either
Dr Demasi pointed out that conflicts of interest extend beyond those who work for the regulators to the advisory panels intended to provide regulators with independent expert advice. A BMJ investigation last year found several expert advisers for COVID-19 vaccine advisory committees in both the UK and the US had financial ties with vaccine manufacturers - ties that the regulators judged as acceptable.
Moreover, whilst there have been improvements in the transparency and accessibility of trial data, most regulatory agencies do not undertake their own assessment of individual patient data, but rather rely on summaries prepared by the drug sponsor. All major regulators also offer "expedited pathways" to approval, paid for by industry fees – representing 36% of approvals in the UK in 2020, 50% in Europe, and 68% in the US.
It has been suggested that the reason many such decisions by the FDA are approved close to their deadline is because reviewers feared jeopardising revenue should they delay beyond it. But such products are more likely to have safety issues. "Accelerated approval processes have resulted in new drugs that were more likely to be withdrawn for safety reasons, more likely to carry a subsequent black box warning, and more likely to have one or more dosage forms voluntarily discontinued by the manufacturer," Dr Demasi said.
'Revolving Door' Between Regulators and Industry
Her paper also highlighted a regulator-industry "revolving door" that has seen many agency officials end up working or consulting for the companies they regulated, meaning that "regulatory capture is not only being baked in by the way in which agencies are funded, but also [how they're] staffed".
She gave the example of Ian Hudson, chief executive of the MHRA between 2013 and 2019, who arrived there having held various senior roles at SmithKline Beecham, and now serves on the board of biotech company Sensyne Health, as well as acting as a senior adviser for the Bill and Melinda Gates Foundation – which has major interests in vaccines and also partly funds the MHRA, as does the World Health Organisation.
In the US, 9 of 10 FDA commissioners between 2006 and 2019 went on to secure roles linked with pharmaceutical companies, and more than a quarter of FDA employees who approved cancer and haematology drugs between 2001 and 2010 worked or consulted for pharmaceutical companies after leaving.
Professor Light said it is no longer possible for doctors and patients to receive unbiased, rigorous evaluations from drug regulators. Non-profit organisations are needed to carry out evaluations of approved drugs independent of industry, he said: "The question is, why weren’t drug regulators doing this trustworthy, transparent, rigorous, unbiased job in the first place?"
He called for a drug and vaccine safety board, independent of the drug regulator, with the authority, staffing, and funds to investigate incidents of patient harm. "Regulators now need their own independent watchdog.
"Countries have independent safety boards for airlines and their passengers. Why not for drugs and patients too?"
Medscape UK has approached the MHRA for comment.
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