EU Approach to Safety: Vox Populi or Vox Dei?

In late February, the European Union announced it was launching a review of its rules on pharma-covigilance. It is not surprising that the EU should decide a review of pharmacovigilance is necessary. This is a constantly evolving discipline requiring constant alertness to how well it is meeting the objectives set for it.

Peter O'Donnell

What is surprising is the way that the EU chose to justify it in the formal announcement. In a statement entitled "Strengthening Medicines Safety Monitoring," it said: "A public consultation shows that the current EU system of medicines safety monitoring (pharmacovigilance) needs rationalization and strengthening."

This suggested a strange approach to medicines regulation, in which public consultation is to be the arbiter of whether pharmacovigilance rules are adequate. Should public consultations, by the same logic, also come to be the mechanisms for deciding on the requirements for clinical trials, or the authorization conditions for medicines—or, indeed, for the delivery of airworthiness certificates for jumbo jets or the approval of nuclear power plants?

There is nothing antidemocratic in this reflection. There are plenty of vivid illustrations to hand that democracy, for all its faults, provides a better system of government than any other system so far developed. In this respect, vox populi—the voice of the people—may be reasonably considered vox dei—the voice of God. But consulting the people on who they want to run a country or a town hall is not the same as consulting the people on intensely technical or scientific matters. Citizens cannot be reasonably expected to make fine distinctions between different reporting procedures for adverse drug events—or to accurately assess the reliability of a fail-safe system for a water cooled reactor. Responsible technical or scientific regulation should respond primarily to technical and scientific considerations. It would be an abdication of responsibility for authorities to leave crucial decisions uniquely to public opinion. The results of a public consultation might be one of many reasons for a regulatory review—but when public consultation is advanced as the determinant trigger of regulatory action, it might suggest that the authorities are losing the plot.

The proposed measures

So much for the process. What of the substance? The EU says that the current EU legal framework is "complex and duplicative" and that "there is a need to clarify roles and responsibilities." Divergent implementation by member states has led to complex and diverse reporting requirements for the industry, according to the EU analysis, and "decision-making at EU level is overly complicated."

The EU aims to strengthen the rules on transparency over pharma-covigilance data, assessment, and decision making and to involve representatives of patients and health care professions more closely. It also envisages clear standards—to be known as "Good Vigilance Practices" (GVP)—for industry and regulators. It wants to simplify both expedited and periodic reporting of suspected adverse drug reactions, matching the reporting requirements with the level of knowledge about the safety of a specific product. A clear legal requirement will be imposed to conduct postauthor-ization safety studies, and decisions on products will be equally and fully implemented across all 27 EU markets.

EU analysis

The new approach will include funding studies into the safety of medicines and into the methodologies used to conduct pharmacovigilance, working with the member states to prevent national administrative practices complicating reporting rules for industry, and boosting coordination by the EU's London-based medicines agency.

The EU analysis at the base of the initiative is that there is abundant evidence of the public health burden that adverse drug reactions cause: Adverse reactions to medicines are "a common cause of death," and "weaknesses in the system continue." Slow and cumbersome action in response to drug safety alerts "puts patient safety at risk."

European Commission Vice-President Günter Verheugen, who is responsible for industry affairs, said: "We will improve and strengthen the monitoring of the safety of medicines so that safety issues are rapidly detected and effectively dealt with on the basis of more robust data." His thinking is scheduled to emerge as a formal legal proposal in 2008. "Rationalization of the EU medicines safety system will free up resources, which can then be directed to better protecting the health of EU citizens," he said.

Only a whiff of populism

The official justification for this initiative, with its emphasis on public consultation and providing better public health protection, has a disconcerting whiff of populism. But closer examination of the proposals suggests a more subtle strategy underlies the EU approach.

For a start, the EU announcement offers no comfort to any simplistic and utopian vision of a world of perfect medication devoid of any awkward safety issues. Instead, it acknowledges frankly that all medicines have some risks, that authorization decisions are a balance of benefits and risks, and that the safety profile of a medicine cannot be fully known prior to authorization.

Then a quick glance at the "public" views on which the approach is based reveals responses principally from patient associations, health care professionals, the pharmaceutical industry, and regulators. This was no opinion survey conducted with clipboard encounters with the man in the street, no straw poll of Joe Public. The views have come from well-informed and sophisticated players, adopting a reasonable and reasoned stance on how to improve pharmacovigilance in Europe.

Crucially, they disclose that the industry input has been hugely influential in the result, with a focus on the need for simplified and consistent mechanisms to eliminate national divergences and duplications. EuropaBio, the biotech industry association, supported harmonized pharmacovigilance procedures and homogenous decision making, with one single framework, one single report, one single European entry for each reporting, and one centralized database. "This single interface," it said, "would save financial resources, without ignoring any safety imperatives, and would allow industry and the authorities to invest in other areas."

The European Federation of Pharmaceutical Industries and Associations (EFPIA) similarly urged one pharmacovigilance system, in one language, with one set of binding rules for all stakeholders, one assessment, and one voice for pharmacovigilance communication. In language that finds its reflection in the EU's February announcement, EFPIA called for "clear and concise, unambiguous provisions that would simplify, strengthen, and provide legal certainty to the EU legislative framework for pharmacovigilance."

Problems voiced

GlaxoSmithKline complained about "the sheer volume of regulations," "contradictory and often unclear procedures" that can be "both complex and confusing," and that "expose individuals responsible for pharmacovigilance in Europe to civil and criminal liability." It called for "the adoption of a single regulation on pharmacovigilance, with clear and concise provisions to provide legal certainty," with "a single set of simplified rules for expedited and periodic reporting of adverse drug reactions in the EU, and a single point for electronic reporting."

Similar problems occasioned by reporting requirements were also raised at a recent European Forum for Good Clinical Practice discussion. Although it did not form part of an official submission, the meeting—on working with ethics committees—demonstrated to EU officials the deep dissatisfaction among clinical trial experts with the current situation. In particular, an overwhelming majority of participants objected to the requirements to send all reports of suspected and unexpected serious adverse reactions to ethics committees, which are, as a result, inundated with raw data that they cannot handle.

Why the "public" tag?

So why, if the proposal is largely industry-friendly, does the EU's February announcement lay such emphasis on public consultation and on public interest? A clue may be found in a comment from EFPIA: "Current negative opinion regarding pharmaceutical companies and regulatory agencies underlines the need for better communication between industry and regulators, and with the media, patient organizations, professional interest groups, and the public on topics associated with the safety of medicines." Decoded, this observation more or less implies that public opinion does matter, because if it is ignored, it can easily become inflamed, and then lead to more draconian controls not only on pharmacovigilance but on clinical trials and authorization in general.

The possibility of such a shift is illustrated by some of the other responses to the public consultation—notably from consumer and health activist organizations. Health Action International (HAI) Europe, for instance, accused the current European pharmacovigilance system not only of weakness but of helping "to sustain the illusion that drug benefits to health hugely outweigh the harms." Penned by inveterate critics of the drug industry, including Charles Medawar and Andrew Herxheimer, the HAI contribution claims that "the present drug regulatory posture involves abuse, by default, of both scientific and democratic first principles," with collusion between regulators and industry, and negligence of broader health issues. It urges immediate involvement in EU regulation of officials who are more health conscious, and less industry conscious.

Such critical comments form only a minority of the inputs to the consultation, but a powerful minority nonetheless, and a potential impediment to the passage of legislation which would simplify the EU rules of pharmacovigilance. EU officials are well aware of the intrinsic volatility of the European legislative process, in which public opinion can often be easily roused when legislation becomes labeled as pro-industry and antipublic. In this case, it seems that an official attempt is being made to head off negative sentiment at the earliest stage, by presenting this largely industry-friendly initiative as primarily citizen friendly. Whether this rather frail subterfuge will have its desired effect remains to be seen. But the fact that the attempt is being made demonstrates in itself that, in many respects, vox populi is already becoming vox dei.

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.