Complete health economic evaluation not possible for all drugs due to lack of data

In the present health economic evaluation IQWiG was commissioned by the Federal Joint Committee (G-BA) to determine the cost-effectiveness ratio of venlafaxine, duloxetine, bupropion, and mirtazapine compared to other currently available drugs and to placebo. For this purpose, the efficiency frontier method, which was adapted by IQWiG and an international expert panel, was applied. With this method, a price or price corridor can be determined within which a drug can be regarded as "cost-effective."

However, due to missing data it was not possible to present the results on an efficiency frontier for all drugs and all patient-relevant outcomes (e.g. quality of life) and derive prices adjusted for added benefit.

Prices markedly higher than appropriate

IQWiG was able to calculate such "added-benefit-adjusted reimbursement prices" for the outcomes "response" (to treatment), defined as a reduction in depressive symptoms of at least 50% on a disease-specific scale, and "remission." The latter is achieved if symptoms can be alleviated to an extent that the criteria for depression are no longer fulfilled.

The relation between their benefit for patients and the price reimbursed by the SHI funds shows marked differences between drugs; this applies to both outcomes. For each of the 4 drugs assessed, the current reimbursement price is higher than the "appropriate" price inferred from the respective efficiency frontier. However, 2 of the drugs assessed (mirtazapine and venlafaxine) have since been classified into a reference price group, meaning that the current price of each drug will probably have shifted closer to the efficiency frontier.

Legal situation has changed

The results of this health economic evaluation are not directly relevant to decision making, neither for drug prices nor for general reimbursement. This is due to a change in the legal situation since the report was commissioned. Originally, the results were supposed to form the basis of the decision on the setting of a "maximum reimbursable price" for drugs. This was the responsibility of the SHI umbrella organization ("GKV-Spitzenverband").

Since the introduction of the Act on the Reform of the Market for Medicinal Products (AMNOG), a health economic evaluation is primarily planned for the case where price negotiations fail after the regular early benefit assessment and where the arbitral verdict is also challenged. In this case the drug manufacturers or the SHI umbrella organization can apply for a health economic evaluation.

Successful test run

Despite the change in the legal situation, it was important for the Institute to complete the report. As the Institute's Director Jürgen Windeler explains: "We wanted to test whether the efficiency frontier method, which is the method preferred by IQWIG, is suitable and leads to robust results. And this test was successful. The report shows drug manufacturers and SHI funds what they can expect from a health economic evaluation and what not."

Challenges remain

IQWiG was also able to gain important experiences in this test run and identify open questions. For instance, it is still debatable how different aspects of benefit and harm, e.g. side effects, should be weighted and aggregated to an overall conclusion. One option is to use patient preferences. IQWiG has therefore tested methods on how to determine such preferences.

In addition, a lack of data was noticeable; on the cost side this applies, among other things, to SHI claims data, which are not freely available in Germany.

But gaps were also evident on the benefit side: on average, studies investigating the benefit of antidepressants lasted only 8 weeks. This time horizon, however, neither sufficiently reflects the treatment situation of patients affected by major depression, nor informs the self-government, as its decisions cannot be based on such a short period.

Important component for decisions in the health care system

Jürgen Windeler is certain that "the results of the health economic evaluation can nevertheless represent an important component in price negotiations and decisions on reimbursement. But we now need a discussion on the relevance of this component for decisions in the health care system. This will also represent a challenge for the new Minister of Health. The discussion also has to address the amount of resources that should be invested. This investment may be considerable, at least as long as cost data are not standardized. However, thanks to the experiences we have gained in the meantime, further health economic evaluations will probably be performed much faster."

The full report can be found at: https://www.iqwig.de/en/projects_results/projects/health_economic/g09_01_health_economic_evaluation_of_venlafaxine_duloxetine_bupropion_and_mirtazapine_compared_to_further_prescribable_pharmaceutical_treatments.1256.html