PharmAccess Leaders Forum 2013 – Conference Highlights
Datamonitor Healthcare attended NextLevel Pharma’s PharmAccess Leaders Forum that took place in Berlin on 16–18 October at which executives from the pharmaceutical industry as well as several EU payers and health technology assessment (HTA) agency representatives discussed the current challenges in achieving sustainable access to medicines in Europe.
HTA agencies must harmonize, says former EMA chief Thomas Lonngren
If more widespread use of HTA in Europe is not a big enough challenge for pharma companies, increasing fragmentation of the HTA process is making achieving access to new medicines an even more difficult and expensive process. Increasingly, separate regions in countries such as Spain and Italy are carrying out HTA analyses for the population they cover and are demanding data proving the value of the technology in a real world setting, increasing the costs for the pharmaceutical companies. Even individual hospitals and primary care units (such as Clinical Commissioning Groups in the UK) are using some form of medicines evaluation when making their own formulary decisions.
Balancing the evidentiary needs of different payers in addition to the needs of the regulators is resulting in an increasing cost burden on manufacturers at a time when achieving acceptable prices for drugs is tough. Moreover, the cost of preparing demanding value dossiers for more extensive assessments, such as the ones carried out by the Federal Joint Committee (Gemeinsamer Bundesausschuss) in Germany under the Pharmaceutical Market Reform Law (AMNOG; Arzneimittelmarktneuordungsgesetz), is acting as a major deterrent to launching smaller products in many markets. In the defense of payers, Vinciane Knappenberg of the Belgian National Institute for Health and Disability Insurance stated that payers require more evidence because of their tight budgets and thus have to be very careful about where they decide to allocate the limited funds. And with needs to see more real world evidence in their specific jurisdictions, this threatens to drive up costs even more.
Speaking at the PharmAccess Leaders Forum, Thomas Lonngren, former executive director of the European Medicines Agency (EMA), said: “Development we have now is unsustainable and we have to do something about it.” He added that it was hoped payers would come together and do what regulators did 50 years ago. “It took us a long time but we got there,” Lonngren said. He also suggested that HTA agencies could take another pointer from the regulators and collaborate on the collection of data from observational studies as the regulators are doing with pharmacovigilance data collection.
However, former and current representatives of several HTA agencies around Europe strongly doubted that European HTA agencies will merge in the short term given the differences in cultures, language, healthcare system infrastructure, and organization, as well as the differing healthcare priorities and willingness to pay. The one factor though that could provide more pressure for the HTA agencies to merge would be if fragmented HTA evaluation were to become no longer financially viable. Several audience members questioned the cost-effectiveness of an HTA analysis for just one region in a particular country.
Professor Finn Borlum Kristensen, chairman of the EUnetHTA executive committee, acknowledged that decision-making will have to stay in the hands of national or regional governments, while the HTA itself as a scientific analysis has the potential to become more homogeneous. "Globalize the evidence, localize the decision" is one of the aims of EUnetHTA, he added. So far, EUnetHTA’s activities have resulted in more widespread HTA use across Europe, especially in countries that previously had no such activities, and have improved transparency of the HTA process, noted Inaki Gutierrez-Ibarluzea of the Basque Office for Health Technology Assessment.
Comparator choice is a moving target
The discrepancies in the advice given by different national payers as to which comparator to use in pivotal trials have been highlighted as a major obstacle by pharma executives. The standard of care not only varies by country but also in time, highlighted Olivier Wong of the French Haute Autorité de Santé. While payers may give the best advice on a comparator ahead of the trials, the one they ultimately request at the time of review may be different, as clinical practice evolves. However, this represents commercial risk that is not unique to the pharmaceutical industry, and the industry should learn to deal with it, he added.
Against this backdrop it becomes clear why pharmaceutical companies may sometimes shy away from asking for early advice from the payers. Their end selection of the trial comparator will largely be governed by commercial decisions such as the impact on the most attractive markets, which may lead to difficulties when the selected comparator goes against the advice of an HTA agency in a smaller market.
Wong further highlighted, though, that not having data for the ideal comparator in France is only an issue if the evidence of additional medical benefit is weak, and does not present an insurmountable obstacle. Nevertheless, Datamonitor Healthcare notes that the situation may be different in Germany, for example, where the lack of flexibility in the choice of comparator and the acceptance of bridging studies have been major sticking points under AMNOG review.
Overall survival vs progression-free survival remains a key sticking point in oncology market access
Speakers at the forum highlighted that the choice of endpoints in oncology drug development remains a key challenge for pharma. Overall survival is still the preferred efficacy measure for payers; however, as speakers from the industry have noted, treatment switching and crossover as well as study length make it difficult to obtain a reliable measure for this endpoint, with progression-free survival (PFS) still the preferred surrogate endpoint in cancer. And while PFS and disease-free survival are acceptable surrogate endpoints for the EMA, they are not considered relevant by several HTA bodies. However, speakers at the forum did add that PFS can be difficult to define and measure within the clinical trial design limitations, and pointed out that choosing validated surrogate endpoints is critical to ensure success as well as demonstrating sizable impact on survival. In situations where cost-effectiveness of oncology drugs is uncertain, speakers from the pharma industry expressed their hopes that payers would be willing to provide the drugs under coverage with evidence development (CED) or similar deals, allowing for real world data collection with the aim of demonstrating value at a later timepoint.
Coverage with evidence development and outcome-based risk shares are too complicated and rarely successful
Risk-sharing schemes, CED, and managed entry agreements are increasingly being used across EU markets as a way of dealing with the uncertainty over the value that medicines bring. However, the experience with such agreements has been rather mixed, and simpler discount agreements have come to dominate.
For example, in Belgium, out of 28 managed entry agreements concluded between the Belgian Commission for Reimbursement of Medicines and the manufacturers since 2010, only 15 had an element of conditional reimbursement with an observational study as a requirement.
And as pointed out by Martin van der Graaff, secretary of the Medicinal Products Reimbursement Committee Healthcare Evaluation Board in the Netherlands, Dutch CEDs resulted in almost guaranteed reimbursement for expensive drugs and can be deemed as a failure as the payers were praying for outcomes rather than paying for outcomes. Difficulties encountered with such agreements include limited duration, incomplete data collection, and changes in treatment algorithms.
Datamonitor Healthcare sees this as a missed opportunity in a world where paying for performance rather than procedures or pills is seen as the Holy Grail. While that approach has the potential to ensure healthcare payers are paying for value delivered, healthcare systems in most countries are not built to work on that principle. Rather, providers are paid for the number of procedures they perform or patients they see. Hence, making risk-sharing schemes or CED and managed entry agreements successful in practice remains tricky, although pharmaceutical companies are keen to enter into an increasing number of such deals. Sticking to simpler schemes and resorting to risk sharing and CED only when there is a real need and a chance of success with the use of registries seems to be the way to go for the payers. As Martin van der Graaff explained, the negative experience in the Netherlands has been useful in terms of redesigning CEDs and registries. Initiatives that start from the bottom up (i.e. physicians) and ones that are co-created by the industry, payers, and healthcare providers have a better chance of success. Moreover, he added that improved collaboration with the EMA in cases where there are post-approval requirements could avoid duplication of work, potentially leading to CED at an EU level.