Implementation of “Coverage With Evidence Development” Drug Approval Strategies Found Lacking

Lessons from Early Deployments in The Netherlands

Lawrenceville, NJ, USA—July 15, 2019—Value in Health, the official journal of ISPOR—the professional society for health economics and outcomes research, announced today the publication of new research from The Netherlands showing important gaps in the deployment of “coverage with evidence development,” a type of pharmaceutical managed entry agreement that gives patients access to treatments while additional evidence is being collected. The report, “Uncertainty and Coverage With Evidence Development: Does Practice Meet Theory?” was published in the July 2019 issue of Value in Health.

Reimbursement decisions concerning pharmaceuticals are subject to uncertainty. Over the years, decision makers have employed a variety of policy measures, called managed entry agreements, to regulate the reimbursement of new, often expensive, healthcare innovations. “Coverage with evidence development” (CED) is one type of managed entry agreement that aims to reduce the uncertainty surrounding the (cost) effectiveness of treatments by granting access to these treatments to patients while additional evidence is being collected.

The Dutch have been leaders in implementing managed entry agreements of various types, including CED. In The Netherlands, CED has been used to regulate the reimbursement of expensive medicines since 2006 and of specific outpatient pharmaceuticals since 2012. Despite the widespread use of CED, evaluation of the value of specific CED arrangements has been lacking.

In order to determine whether the practical implementation of CED in The Netherlands has included all the crucial steps for successful implementation, the authors examined the first 3 CED schemes that were completed in The Netherlands. The initial and final assessment dossiers for these cases have been published on the Dutch Health Care Institute (Zorginstituut Nederland) website:

  • Alglucosidase Alfa (Myozyme®) for the treatment of Pompe’s disease
  • Rituximab (MabThera®) for the treatment of rheumatoid arthritis
  • Trastuzumab (Herceptin®) for the treatment of human epidermal growth factor receptor 2 positive early breast cancer

The findings were disappointing. Unfortunately, in these 3 CED implementations, uncertainties were neither systematically nor completely identified. Furthermore, the analyzed dossiers did not justify why specific outcomes were not included in the CED research plan.

“These findings support the need for a more systematic approach to identify uncertainties in assessments and to explore the impact of these uncertainties on the results and decision making,” said author Xavier G.L.V. Pouwels, MSc, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre+, Maastricht, The Netherlands. “Such an approach should rest on a clear definition of uncertainty and its sources. A framework would help to systematically identify uncertainty, and this process should involve all stakeholders. Value of information analysis, and the uncertainties that are not included in this analysis, should inform CED research design.”


ISPOR, the professional society for health economics and outcomes research (HEOR), is an international, multistakeholder, nonprofit dedicated to advancing HEOR excellence to improve decision making for health globally. The Society is the leading source for scientific conferences, peer-reviewed and MEDLINE®-indexed publications, good practices guidance, education, collaboration, and tools/resources in the field.
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Value in Health (ISSN 1098-3015) is an international, indexed journal that publishes original research and health policy articles that advance the field of health economics and outcomes research to help healthcare leaders make evidence-based decisions. The journal’s 2018 impact factor score is 5.037. Value in Health is ranked 4th among 81 journals in health policy and services, 5th among 98 journals in healthcare sciences and services, and 11th among 363 journals in economics. Value in Health is a monthly publication that circulates to more than 10,000 readers around the world.
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