Deconstructing Relative Effectiveness Efforts

An apparently innocuous announcement in July about the membership policy for a little-known European organization could turn out to be big trouble—for the pharmaceutical industry in general and the clinical trials community in particular.

Peter O'Donnell

The announcement came in the form of a draft "stakeholder involvement policy" for the EUnetHTA Joint Action 2010-2012. "Stakeholder involvement policy" may need little explanation. It consists of principles and criteria governing the admission of different groups. The EUnetHTA Joint Action merits some greater exegesis.

EUnetHTA is the outcome of a collaboration among nearly 30 European governments focused on scientific cooperation in health technology assessment (HTA) in Europe. It isn't a new outfit. It's been on the go since 2006, extending the scope and increasing the density of its network "to help developing reliable, timely, transparent, and transferable information to contribute to HTAs in European countries," according to its own account of itself.

But now it's moving into a new gear. The joint action it is now launching is a large-scale operation with significant funding from the European Union. And it is explicitly aimed at developing a Europe-wide approach to assessing relative effectiveness of medicines. "The need for closer collaboration in HTA has been identified by HTA doers [sic] themselves," it remarks in its mission statement. This inelegantly defined group of "HTA doers" may very well be convinced of the need for closer collaboration. But despite their hijacking of authority on the subject, they are not the only game in town, or the only view of the subject.

HTA is not as easy to do as it is to say. Opinions about its merits continue to diverge widely—not just over how it should be done but even over whether it should, in its current guise, be done at all. For many in the pharm-aceutical industry in Europe, it still represents the thin end of a wedge that could prize open the tabernacle containing the orthodox criteria for drug authorization. The trio of quality, safety, and efficacy has lain sacrosanct there for decades. Now HTA risks desecrating them by adding the vulgar consideration of cost.

Of course, there is an argument that it is not unreasonable that the people who are going to pay for new treatments might like to check them out within the context of what else is available. But even those who make this admission remain deeply divided over what is the right way to go about such an evaluation.

Everyone reading this journal is more than familiar with the challenges of demonstrating the ultimate potential efficacy of a new product on the basis of clinical trials alone. But at present, and as long as the only criteria are the intrinsic quality, safety, and efficacy of the product, the trial data can be sufficient to win authorization for limited indications, allowing launch and opening up the prospect of widening use with widened knowledge about the product in wider patient populations.

If the authorities' yes-no decisions on authorization are to be based on whether that new product can demonstrate—on the basis only of limited use in trials—a superior cost/efficacy performance to competitors already on the market, the challenge is all the greater.

Add to that the peculiar challenge faced by everyone in Europe—that each country still sticks to its own culture and traditions. So assessments, and the baselines against which assessments are made, will vary accordingly from country to country. Such diversity, already sufficiently in evidence in national views based just on the sacred three criteria, will be intensified as soon as relative efficacy is thrown into the mix.

This provokes a raft of questions over whether it might be better to seek agreement on an EU-level approach, and on what basis, or to accept that the range of views in Europe is at present too great to allow for an EU-wide solution.

Work is underway in numerous forums in Europe and beyond to tease out the problems surrounding HTA. One option might be to seek a common European-level approach. But it might not be the right option at present. Some senior industry executives are raising the question as to whether it is appropriate to be racing ahead with HTA when the scientific grounds for decisions remain at present very contentious. This may sound rather unEuropean, but the precedent was set only days ago in the EU, when senior officials proposed that on the—equally contentious—question of GMO authorization, each member state should in effect be allowed to go its own way until more consensus emerges on the underlying issues.

No less a figure than Andrew Witty, Chief Executive Officer of GlaxoSmithKline and President of the European Federation of Pharmaceutical Industries and Associations (EFPIA), has also called some of the easy assumptions about HTA into question. Speaking in London in June, he acknowledged the "budgetary constraints" facing governments, and the "increasing desire to identify value in order to make difficult funding decisions." But, he went on, "What matters is whether a medicine works, responds to patient needs." If it does, he said, then what else matters is "that it is rewarded."

Choosing his words carefully, he recognized that the industry's products "must offer demonstrable added value." But he insisted that a "common, shared understanding of value was critical to the industry and governments."

Against this background, the enthusiastic embrace of "closer collaboration" by the EUnetHTA Joint Action may be a little glib. It seems to suggest that a destination has already been decided upon, despite the fact that, to pursue the metaphor, there is no consensus on whether to make a journey, the compass has yet to be invented, new lands are still being discovered, and there is still no map of the terrain.

Confidence in the venture is not reinforced by the claim that the EUnetHTA Joint Action makes for its heritage. It builds, it says, on "the achievements of a number of the previous European initiatives," including notably the EU's Pharmaceutical Forum and its attempts to move ahead with relative effectiveness. This column has had occasion in the past to pour scorn on the Pharmaceutical Forum—one more episode in the seemingly endless (and endlessly circular) European debate on funding pharmaceuticals, opposing industry against a range of health insurance agencies, health ministries, health professions, and health activists.

Its analysis was often vague, its results were far from clear, its views were far from incisive—and its influence was accordingly limited. Like so many of its predecessors (and they stretch back to long before the creation of this journal), the forum claimed to have found valuable compromises, when all it had really done was to offer a fudge by concealing differences behind ambiguous language.

The EUnetHTA Joint Action network, in its just-released stakeholder involvement policy, says it will "seek various types of input from stakeholders" since "HTA and its use are of interest to a variety of groups and organizations." So "to allow for a broad approach to its stakeholder base," the EUnetHTA Joint Action intends to define "stakeholder" as "groups or organizations which provide considerable insight into stakeholder views and will be affected by or have an interest in and may in a consultative role influence on the actions or aims of an HTA organization, project or policy direction."

It has identified as "particularly important" the following groups (and in the following order): patient and health care consumer organizations; health care providers (professionals and hospitals); payers; industry; health related media; and "different forms of stakeholder involvement."

It is, of course, good to see industry included (how could it not be included?). But the hierarchy established by the listing already signals something about where the weight of the arguments are expected to lie. And even allowing for the current fashion for making everything "patient-centered," it is difficult to see why a discussion essentially about cost should give precedence to patient and health care consumer organizations and health care professionals and hospitals over the organizations that pay for medicines. In the same vein, it is harder still to see why "health-related media" should be involved at all—and who on earth will be covered (or more to the point not be covered) by "different forms of stakeholder involvement?"

Such imprecision would be considered unacceptable in work related to assessing the performance of an airplane or the safety of a suspension bridge. Is it any less unacceptable in the equally technical field of discussing the value of medicines?

But if the conclusions that emerge from this venture are as ill-considered as this particular exercise, not only will medicines manufacturers find it harder still to argue their case for a reasonable reward for their products, the clinical trial community too will find the basis of its own current work undermined, and could be obliged to shift its strategy and resources toward meeting new and possibly arbitrary requirements imposed as the consequence of a confused debate.

Watch this space.