European Medicines Agency accused of censoring researchers over drug safety analyses
Scientists are concerned that plans to control the way in which independent researchers use drug safety data could hinder their research.
Source: Malcolm Chapman / Shutterstock.com
The European Medicines Agency (EMA) has been accused of censorship over proposals to control the way independent researchers use drug safety data held in its EudraVigilance database, which holds all suspected adverse drug reaction (ADR) reports on medicines in Europe.
Scientists are concerned that the EMA’s plans to view any publication that uses the data before submission amounts to censorship and is impractical for researchers.
The database contains more than seven million ADR reports, increasing by around one million each year, and forms the backbone for drug safety monitoring in Europe. Of the drug safety signals reviewed by the regulator in 2013, more than 90% originated from the database.
The EMA is consulting on how to revise its policy on access to EudraVigilance until 15 September 2014. The consultation document says an EMA panel will review individual research requests for access to data in the database.
The regulator may refuse access if the panel remains “unconvinced” of the public health value of the proposed research or decides it conflicts with its “public health and legal responsibilities”.
The EMA also says it has the “right” to view any publication resulting from EudraVigilance data before submission — the maximum period for initial agency review will be six weeks, including a privacy check regarding possible re-identification of patients.
“Any issues raised by the agency concerning incorrect analyses, unsupported inferences, misleading statements or the protection of personal data must be addressed to the satisfaction of the agency before submission for publication,” the EMA says.
A disclaimer must be added to manuscripts and the EMA reserves the right to reword it in “cases of unresolved disagreement over the interpretation of the data”.
However, scientists have expressed concerns about the proposals.
“If there are flawed analyses, or over-interpretation of [medicine] risk signals, then that is a matter for public discussion and debate, not censorship by the medicines regulator,” says Ben Goldacre, co-founder of the AllTrials campaign, which has been advocating that all clinical trial results should be published.
Source: Ben Goldacre
“[The EMA] says they should be allowed to suppress anything in an academic paper that they regard as ‘incorrect analyses, unsupported inferences, [or] misleading statements’. This is a profoundly outdated world view,” he adds. “Simply because they are the body collecting this public data from EU patients does not give them the right to control how it is used. This seems to simply represent state censorship of scientific discussion and data analysis of public health data.”
Goldacre argues that it puts the EMA in a position of conflict as it is likely that some analyses may draw attention to the regulator’s own drug decisions, which he claims are often close calls.
“It is quite wrong that the EMA should be given the right to censor analyses critical of their own analyses,” says Goldacre, who is a Wellcome research fellow in epidemiology at the London School of Hygiene and Tropical Medicine.
Another co-founder of AllTrials, Carl Heneghan, director of the Centre for Evidence-Based Medicine, says the protection of personal data is warranted but believes the plans are flawed.
“[The agency] will require a significant team of statistical reviewers and will find itself embroiled in numerous longwinded disputes. Indeed, to come to the conclusion that analyses are flawed will require the agency to openly publish these analyses for independent scientific scrutiny,” he argues. “Consequently, what it is proposing is unworkable, and what is clear is regulators are using these measures to prevent more open scrutiny of its databases. This is unacceptable and will lead to delays and inappropriate use of resources.”
Source: Carl Heneghan
Heneghan says the regulator needs to give examples of how incorrect analyses, unsupported inferences or misleading statements have been dealt with in the past and what it means by these terms.
“Providing transparent and timely information should be a priority of regulators if the full benefits and harms of treatments are to be realised. I continue to be surprised and perplexed that the EMA, as a public body, doesn’t think this is a fundamental priority of its work,” he adds.
Andrew Herxheimer, an emeritus fellow of the UK Cochrane Centre and convener of the adverse effects methods group at the Cochrane Collaboration, which publishes systematic reviews on drug safety and efficacy, argues that the EMA’s access policy is unrealistic.
“To get the protocols [of systematic reviews] checked by the EMA each time is not on,” he says. “It is cumbersome and impractical. What are they worried about?”
Jayne Lawrence, the chief scientist of the Royal Pharmaceutical Society (RPS), says that access to the database is a “big step” in the transparency arena for the EMA.
While Lawrence says there needs to be a sense check before analyses are published to avoid scaremongering around the safety of drugs or misrepresentation of data, she acknowledges that there might be a conflict of interest if the EMA does this check.
“In an ideal world, the peer review process that medical journals use should pick up unsound research, but this has been shown to fail on occasions,” she says.
Lawrence suggests that it would be better for an independent party to review analyses prior to publication.
Regulators have often argued against unlimited access to their data, saying that clinicians may be confused by poor quality or contradictory analyses of patient data. However, Goldacre thinks this concern is not proportionate to the risk.
“There are 28,100 scientific journals in print today, with over a million articles published each year, and over 23 million papers indexed in PubMed to date,” he says. “Work of poorer quality is routinely conducted and published already. It is managed — to a reasonable degree — in the academic ecosystem of evidence synthesis and critical appraisal, before it can impact on practice.”
Goldacre believes any harm that could theoretically arise from an increase in weak academic publications must be balanced against the huge benefits of wider access to patient data.
The EMA says this is not new policy. “Information on ADRs is complex and only one part of the overall safety information that inputs to the benefit/risk assessment of a medicine,” says a spokesperson. “The EMA and the national medicines regulators in the EU have been assigned the responsibility to make these evaluations on behalf of the public.”
The spokesperson says the process allows the EMA to offer insight to researchers on particular aspects of the design or conclusions of their research.
“This does not in any way prevent the researchers from proceeding and publishing, but is rather an opportunity for a review,” she says. “Publications can have major impact on [the] use of medicines and public health and it is in everyone’s interest that they are done with a clear understanding of the data.”
In the past, the agency has resisted releasing certain clinical and safety data but complied after complaints were upheld by the European Ombudsman. Such cases include requests for clinical data on obesity drugs by Danish researchers at the Nordic Cochrane Centre, and suspected ADRs to acne drug isotretinoin and the antibiotic co-trimoxazole Septrin.
In February 2012, Guido Rasi, the newly-appointed executive director of the EMA, said he was keen for transparency, insisting that all clinical data, including ADR reports, are not commercially confidential; there is only data protection from a patient’s point of view. The pharmaceutical industry defended the route taken by the regulator.
“The draft seems to balance the legitimate need for improved transparency with safeguards to protect patient privacy and integrity of decisions by regulatory agencies,” says Richard Bergström, the director general of the European Federation of Pharmaceutical Industries and Associations (EFPIA).
He argues that access to data comes with certain responsibilities.
“Physicians and patients may be reluctant to report side effects if there is a fear that their identities would be made public,” he adds. “Similarly, there is a responsibility for researchers to apply high scientific standards.”
If a pharmaceutical company wants to draw conclusions from data, whether on benefit or risk, those conclusions must be approved by the regulator, explains Bergström. It is logical, therefore, that independent researchers have to substantiate new findings before they are made public.
Bergström points out that there have been examples in the past where “bad science” has impacted on public health.
“The best-known case is when many UK parents were persuaded, based on a publication that was later withdrawn, not to let their children take the MMR vaccine — many years later contributing to the 2012–2013 measles epidemic in Wales and elsewhere in Britain.”
Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.20066108
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