Europe in HTA Gridlock

Much like a bus stop, you wait for ages for an international review of health technology assessment to come along ... then two turn up at once.

One emerged in mid-July in the shape of a study written by Charles River Associates and sponsored by some of the big beasts among the world's drug industry associations: EFPIA, EuropaBio, Medicines Australia, and PhRMA. This was unsurprisingly critical of many aspects of the current arrangements for health technology assessment (HTA), pointing to numerous "inefficiencies and inconsistencies" in the 15 jurisdictions it covered, in Europe, Australia, and the United States. "The most significant observable impact of the HTA process is imposing restrictions on the use of a particular medicine," the study comments.

Senior industry figures have repeatedly underlined their concerns that HTA may prove a dangerous weapon rather than a valuable tool if it falls into the wrong hands or is operated carelessly. Glaxo- SmithKline CEO Andrew Witty said recently that the industry is "in an awkward position as countries are doing it in different ways." He is apprehensive that these national systems will become increasingly demanding in the information they seek for their national validation. "This will lead to fragmentation of the assessment of relative and clinical effectiveness, and that will be unsustainable," in Witty's view. EFPIA complained earlier this year that the challenge of diverse national requirements "is further compounded by lack of alignment among HTAs, and between HTAs and regulators, about what value is and, more specifically, how it can be appropriately assessed."

So, as might be expected from a study that industry has paid dearly for, potential risks figure prominently. A "poorly designed or managed HTA process runs the risk of denying patients appropriate access to medical technologies, inefficiently allocating resources, constraining clinical freedom, and sending distorted signals to medical technology providers," the study warns on its opening page.

It then goes on to list a string of inadequacies in the current arrangements. "Methodologies greatly vary across systems," and the economic aspects are often "subject to intense academic discussions," it says. "The range of evidence accepted by different HTA varies across countries," and "there is little evidence of societal value being taken into account in assessments examined." On top of that, "mechanisms to account for uncertainty are currently fairly limited," and industry has little recourse to any "independent appeal process."

Not only are the mechanisms inconsistent, but—worse still, the study suggests—so too are the outcomes: "HTA processes lead to different results in terms of recommendations for coverage, including potential restrictions for the same products." And "little evidence can be found that HTA on average resulted in higher rewards for higher value medicines."

Significantly, the industry report fails to even consider a contrarian view: that disarray in HTA approaches and methodology can actually benefit companies by allowing several "bites at the apple" and the opportunity to rectify a single bad judgment elsewhere.

No Ringing Endorsement

Meanwhile, the European Network for Health Technology Assessment (EUnetHTA) has published its own report. It trumped the industry-backed study by analyzing 26 European jurisdictions, Australia, Canada, the US, and New Zealand. This is very definitely not an industry-inspired report. EUnetHTA is a very different type of organization, bringing together at European level a host of national health insurance organizations, academia, government agencies and health ministries, and national and regional health authorities. Its views, therefore, are not colored by any conspiracy theories, or any fears of HTA turning into a stick that will beat its members into submission, or worse.

And what does it conclude? "This review has indicated that although the reimbursement processes differ between jurisdictions, the methodology that is used for the comparative analysis is rather similar," it says. It concludes that there is sufficient common ground for the development of a shared methodology for relative effectiveness assessment of pharmaceuticals.

A contrary view to the industry study? Not altogether. For a start, the EUnetHTA report does not constitute (and nor was it intended to be) a straight rebuttal of the industry-sponsored study. Its range of reference is more restricted, since relative effectiveness assessment does not cover the entire field of HTA—notably omitting cost and economic considerations. In European Union discussions of HTA, relative effectiveness is considered as a separate issue from cost-effectiveness, so since cost-effectiveness is excluded, the EUnetHTA study's findings are accordingly limited in one of the areas that is of most interest to the pharmaceutical industry.

Issues Galore

And not unlike the industry study, the EUnetHTA report also reveals a wide range of differences in national approach, even within its slightly tighter scope. It remarks, for instance, on the "variation between jurisdictions in the terminology and definitions that are used for similar processes." Further potential complications are signaled in "variations in interpretation due to cultural and legislative differences," and as a result of language barriers—which are an inevitably complicating factor in any European discussion, since the European Union alone operates in more than 20 official languages. These variations, it continues artlessly, "may lead to confusion on whether jurisdictions are actually doing the same thing," adding, equally ingenuously, "in order to develop common methodology it will be essential to be clear about the wording and the content of definitions."

Another weakness that EUnetHTA acknowledges in its own conclusions is that "methods to do the assessment are in general not explicitly reported—on issues as crucial as which endpoints can be used, or the level of evidence required." It plans to remedy these deficiencies with a series of guidelines. But these are not yet complete, still less in place.

In the background, too, there is "confusion" and "a debate ongoing on whether a benefit/risk assessment (the balance between doing more good than harm) is part of a relative effectiveness assessment." As EUnetHTA observes, some authorities advocate leaving benefit/risk assessment strictly to the registration procedure, while others want it to be included in the relative effectiveness assessment.

Another area of divergence is that "whether the weighting of the intended and unintended effects is part of the assessment or is explicitly limited to the appraisal phase." And while "in many jurisdictions the definition for the choice of comparator is similar to 'usual care,' the choice of comparator may differ between jurisdictions, as usual care can differ between jurisdictions."

So although EUnetHTA champions the development of a shared methodology, it openly recognizes that "our results also show that there are still a number of issues to be dealt with before it can be introduced."

A hands-down, two-to-zero victory for the industry case, then? Not really. Because the industry-sponsored study is itself ambivalent, suggesting that it is "generally agreed" that HTA can be valuable. Even the industry's own spin on the study, in a statement accompanying its release, recognizes that "there are reasons to be optimistic." The industry's optimism springs from the fact "most HTA systems are still in development or are evolving."

Industry is evidently determined to intervene more vigorously than it has done so far in the debates over HTA. Part of the industry reticence until now has been the consequence of its own lack of information on the issues that matter to it. On the principle that you don't go into a gunfight waving a weapon if you have no ammunition, industry has limited itself largely to consultations, interspersed with communicating a sense of unease through muttering imprecise warnings. This is clearly about to change. The industry says that its study "sets the foundation for a regular exercise, which will receive continuous support from the four trade associations."

This, it believes, will "allow consistent assessments of the impact of HTA to be efficiently captured over time." It will make it possible in this complex environment to "take into account the impact of current reforms and cross-border activities on access to innovative medicines and the move towards truly patient-centred healthcare systems." In other words, industry is aiming to fill its ammunition belt ready for the fray.

And a fray can be expected to gather in intensity over the coming months—certainly in Europe, and probably more widely. European governments have clearly indicated their readiness to get pharmaceutical spending in a tighter grip—and many of them are already doing so. HTA will play a central role in the debates over drug pricing and reimbursement and drug access, and industry naturally wants to ensure it has answers for all the questions that will arise. But the EUnetHTA initiative is also rumbling forward too. So if you are waiting hopefully at the HTA bus stop, you can be sure that there will be a whole lot of new reports coming along soon.

Reflector is Pharm Exec Europe's anonymous columnist, a commentator so close to the action in Europe that his identity must remain secret.