Paris, 28 February 2020

In a published response to the article "Pathways to independence: towards producing and using trustworthy evidence" published online at bmj.com (> BMJ 2019;367:l6576), Prescrire argues that public funding and elimination of industry capture of medicines agencies are crucial pathways to independence, essential to better serve patients, healthcare professionals and the public.

> Read this response online at bmj.com

Response to "Pathways to independence: towards producing and using trustworthy evidence"

Moynihan and colleagues are investigating pathways for the production and the use of trustworthy evidence free from financial conflicts of interest in medical research, education and practice. Corporate influence on the policy and decision-making process needs more scrutiny.

1. Public funding of medicines agencies is crucial for their independence

According to the announced European Medicines Agency (EMA) budget for 2020, around 86% derives from fees and charges from industry, 14% from the European Union's contribution for public health issues and less than 1% from other sources (1). The European Commission Inception Impact Assessment on the revision of the EMA fee system cites similar figures: 90.2% of the Agency's total budget funded by fees from pharmaceutical companies and around 9.6% by EU/EEA budget contributions (2). As for the U.S. FDA's human drug regulatory activities, industry user fees provide 65% of the funding (3).

• Industry fees undermine the independence of drug regulatory agencies

Fees for services make drug regulatory agencies dependent on funding from the industry that they are supposed to regulate. This is an obvious conflict of interest. Health authorities have a responsibility to act objectively and in the public interest, without being swayed by the business concerns of companies who are seeking product approval or who are “regular clients” within the framework of post-marketing follow-up.

For the sake of independence, and to carry out its public health mission, the EMA needs to be weaned off its fee-for-service relationship with pharmaceutical companies and funded through public funding from the European Union. The upcoming revision of the EMA fee system represents a great opportunity for exploring options of adequate public funding and to make steps towards greater independence (4).

The principle of the independence of European Medicines Agency must be safeguarded, to ensure that the business interests of pharmaceutical companies do not override public health interests.

2. Eliminate industry capture of medicine agencies and authorities

• Scientific advice

Situations exposing EMA staff and experts to the risk of institutional capture that could compromise their impartiality and objectivity should be avoided. Repeated contact between pharmaceutical companies and EMA representatives long before submission of a marketing authorisation application can lead to institutional capture and the potential for corporate influence that goes against the public interest.

As stated in EMA's annual report for 2018, “EMA and its scientific committees and groups of experts from the EU national competent authorities are fostering early interaction and dialogue with developers to facilitate the development process, and help companies to collect adequate data and comply with regulatory standards” (5). Due to the large increase in companies' requests for pre-submission scientific advice from medicines agencies (and Health Technology Assessment bodies) there are growing concerns that this practice might exert control from an early stage over everyone involved in the assessment of marketing authorisation applications at both national and European levels.

In follow-up of a strategic inquiry, the European Ombudsman came up with suggestions for improvement in July 2019 (6). The Ombudsman called for “a separation between those responsible for providing scientific advice …and those subsequently involved in evaluating a marketing authorisation application for the same medicine”. The Ombudsman also suggested that EMA attach “to the EPAR a detailed log of all relevant pre-submission activities, including the names of the experts involved”.

There is little transparency over the content of requests for pre-submission scientific advice and the answers provided. The publication of this information would greatly facilitate independent research on the provision of scientific advice and evaluation of its impact. Currently, only pharmaceutical companies and EMA itself are in a position to evaluate the impact of early scientific advice, yet patients and health professionals are directly affected. Access to the questions raised would help clarify pharmaceutical companies' needs and concerns when designing clinical research programmes. For the sake of scientific rigour, impartiality and neutrality, EMA should make its scientific and procedural requirements clearer in guidelines on clinical research being publicly available. This would be a useful step towards information sharing and greater transparency. It would also help to improve existing guidelines by specifying or clarifying exactly what assessors need from clinical research.

• Influence on policy regulation

EMA's many close contacts with the pharmaceutical industry have an impact on policy regulation. The proposed objectives/recommendations outlined in the recent consultation paper on regulatory science were mainly driven by industry, science or technology, with little focus on clear regulatory merits and responsibilities. There is a continuous trend towards early interactions between companies and EMA, such as scientific advice, flexibilities and faster marketing authorisations with a shift from pre-marketing approval evidence-collection towards an unclear post-approval assessment (7).

Transparency, robust and independent assessments of medicines free from vested interests and full access to clinical data should be a priority for the benefit of patients, healthcare professionals and the public in general.

> Read this response online at bmj.com

©Prescrire 28 February 2020

References:

1. https://www.ema.europa.eu/en/about-us/how-we-work/governance-documents/funding
2. https://ec.europa.eu/health/human-use/legal-framework/ema_impact-assessment_en
3. https://www.fda.gov/media/131874/download
4. https://english.prescrire.org/en/79/207/46302/6187/5953/SubReportDetails.aspx
5. https://www.ema.europa.eu/en/documents/annual-report/2018-annual-report-european-medicines-agency_en.pdf (see p. 44)
6. https://www.ombudsman.europa.eu/en/decision/en/116683
7. https://english.prescrire.org/en/79/207/46302/6127/5953/SubReportDetails.aspx
    

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