Do innovative medicines against cancer always have a real added value?

Neyt M, Devos C, Thiry N, Silversmit G, De Gendt C, Van Damme N, Castanares-Zapatero D, Fairon N, Hulstaert F, Verleye L
Record ID 32018004275
Authors' objectives: The research questions of this report are as follows: • First research question: What is the evolution in overall survival in a broad selection of oncology indications and the budget impact of introducing new cancer drugs in the last 15 years? • Second research question: What is known in the literature about the benefits (e.g. impact on overall survival and QoL) and cost-effectiveness for a broad selection of new cancer drugs? Next to providing an answer to these research questions, we also aim to formulate areas for improvement. Therefore, different topics are tackled in the discussion of this report. Our policy recommendations are published in a separate synthesis, which is published simultaneously with this report.
Authors' results and conclusions: The findings in the literature and this study reinforce each other. Evaluations of EMA and FDA dossiers point to major uncertainties about the added value of innovative cancer drugs when they receive their marketing authorisation. The studies also indicate that many of these uncertainties are not answered after several years, or that the added value is often limited in reality. Our observational Belgian data show that substantial improvements in survival have often not been observed in the last 15 years for many of the 12 studied indications, while new drugs with increased expenditure have been introduced. There are also the cited shortcomings in measuring and identifying the impact on quality of life, the (too) great confidence in surrogate endpoints, etc. These uncertainties about the added value of innovative medicines are also combined with secret contracts about their price that makes the system completely non-transparent. It is now up to the European and (inter)national governments to seriously question this system and to decide how they want to use it in the future. In the first place, we recommend that it evolves into a system that tries to resolve clinical uncertainties and clearly map out the real added value for the patient of new interventions compared to existing treatments. This is an essential objective if policy-makers, doctors and patients are to be well informed and able to make decisions on a reliable basis. The findings in this study based on the (recent) past can help policy-makers improve policy in the future. We would like to refer to our recommendations, which are aimed at European and (inter)national governments, doctors and patients.
Authors' recommendations: To the European Commission, the European Medicines Agency (EMA) & the NIHDI: 1. We recommend not focusing primarily on early access to “innovative” oncology drugs. The primary concern should be to provide timely access to medicines for which clear and reliable added value for the patient has been demonstrated. Below we give concrete recommendations to achieve this goal. To the European Commission, EMA & companies: 2. We recommend conducting studies already in the pre-marketing phase that are suitable for registration purposes, reimbursement decisions and support for physicians and patients when taking decisions about treatments. Since it is more difficult to provide additional evidence of effectiveness after marketing authorisation was granted, it is crucial to start the necessary studies in a timely manner. 3. In designing these studies, we recommend that there is more focus on including the correct (active) comparator(s), relevant endpoints (including overall survival and quality of life) and adequate follow-up without inappropriate crossover of patients. o A close collaboration of HTA agencies/payers with the support of EMA for this approach to start up practice-relevant studies in the pre-marketing phase must be legally anchored in European law (see recommendation 5). o Given the often uncertain and limited added value of cancer drugs, randomised studies must be prioritised as the most reliable source for estimating the added value of new interventions. Non-randomised observational data should not simply be regarded as a reliable study design for estimating the treatment effect. o These randomised trials should pay due attention to the following: -Including a population that reflects the future target population. - Incorporating the standard treatment as a comparator. Elements of treatment optimisation (e.g. the duration of the treatment) should also already be evaluated in the pre-marketing phase - Relevant endpoints are quality of life and survival. These should be included in the studies where possible. - Surrogate endpoints can only be useful where they are sufficiently scientifically validated for the specific condition and mechanism of action of the drug. We recommend following the EUnetHTA guideline whereby data on overall survival as well as quality of life should be systematically collected in the metastatic setting (stage IV). - Measuring quality of life, using both disease-specific and generic utility tools (as also recommended by EUnetHTA). Quality of life should also be measured throughout the full follow-up of the study (e.g. also after disease progression). - Strictly avoiding inappropriate crossover of patients in the study. 4. We recommend strict monitoring regarding the timely and complete reporting of all study results. For example, the impact on quality of life must be reported transparently (i.e. results for all treatment arms and all time points when this outcome was measured). The full results of clinical studies should be made public and never be confidential. Like other key endpoints, quality of life and overall survival should be included in the EPAR (European Public Assessment Report). To the Minister of Public Health and the European Commission, regarding EMA: 5. We recommend that the European Commission adjust the regulatory framework for the EMA, while respecting the difference in competences between the EMA and the national authorities. It should be enshrined that through mandatory early dialogues, the input of the payers and HTA bodies in the member states is taken into account when drafting the protocol of the confirmatory clinical trials. This will help to prevent the studies designed from not providing the information needed to support subsequent reimbursement decisions (see also recommendations 2 and 3). 6. We recommend the European Commission urging the EMA to make more selective use of conditional marketing authorisation if evidence as to the treatment's effect is insufficient. This approval must then be made conditional, with an explicit requirement to collect the required data within a certain period. Conditional approval should be automatically withdrawn if the necessary studies are not initiated/continued/delivered. This should be sufficient incentive to deliver the required data on time. It should be further investigated which criteria can be used for the selective application of the conditional market authorisation and how compliance with the conditions imposed can be monitored. To the NIHDI: 7-11 To the BCR & NIHDI: 12-15 To physicians, nurses, patients, patient representatives and independent research institutions: 16-18 To all actors in society, including patient representatives, healthcare providers, industry, policy makers, the general public, etc.: 19
Project Status: Completed
Year Published: 2021
URL for published report:
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Belgium
MeSH Terms
  • Antineoplastic Agents
  • Therapies, Investigational
  • Technology, High-Cost
  • Antibodies, Monoclonal
  • Immunotherapy
  • Costs and Cost Analysis
  • Neoplasms
  • Technology Assessment, Biomedical
  • Drug Costs
Organisation Name: Belgian Health Care Knowledge Centre
Contact Address: Administrative Centre Botanique, Doorbuilding (10th floor), Boulevard du Jardin Botanique 55, B-1000 Brussels, Belgium tel: +32 2 287 33 88 fax: +32 2 287 33 85
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Copyright: Belgian Health Care Knowledge Centre (KCE)
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.