Defining ‘therapeutic value’ of medicines: a scoping review

ObjectivesIn recent years, discussions on the importance and scope of therapeutic value of new medicines have intensified, stimulated by the increase of prices and number of medicines entering the market. This study aims to perform a scoping review identifying factors contributing to the definition of the therapeutic value of medicines.DesignScoping review.Data sourcesWe searched the MEDLINE, CINAHL, Embase, Business Source Premier, EconLit, Regional Business News, Cochrane, Web of Science, Scope and Pool databases through December 2020 in English, German, French, Italian and Spanish.Eligibility criteriaStudies that included determinants for the definition of therapeutic value of medicines were included.Data extraction and synthesisData were extracted using the mentioned data sources. Two reviewers independently screened and analysed the articles. Data were analysed from April 2021 to May 2022.ResultsOf the 1883 studies screened, 51 were selected and the identified factors contributing to the definition of therapeutic value of medicines were classified in three categories: patient perspective, public health perspective and socioeconomic perspective. More than three-quarters of the included studies were published after 2014, with the majority of the studies focusing on either cancer disorders (14 of 51, 27.5%) or rare diseases (11 of 51, 21.6%). Frequently mentioned determinants for value were quality of life, therapeutic alternatives and side effects (all patient perspective), prevalence/incidence and clinical endpoints (all public health perspective), and costs (socioeconomic perspective).ConclusionsMultiple determinants have been developed to define the therapeutic value of medicines, most of them focusing on cancer disorders and rare diseases. Considering the relevance of value of medicines to guide patients and physicians in decision-making as well as policymakers in resource allocation decisions, a development of evidence-based factors for the definition of therapeutic value of medicines is needed across all therapeutic areas

Therapeutic Value of Drugs Granted Accelerated Approval or Conditional Marketing Authorization in the US an Europe From 2007 to 2021

IMPORTANCE: The number of drugs approved through the accelerated approval or conditional marketing authorization pathways has increased with unclear evidence of their therapeutic value. OBJECTIVES: To assess the therapeutic value of drug indications granted accelerated approval in the US or conditional marketing authorization in the European Union (EU) overall and for cancer indications. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the public databases of the US Food and Drug Administration and the European Medicines Agency to identify all drugs (initial and supplemental indications) granted accelerated approval in the US or conditional marketing authorization (initial indications only) in the EU between January 1, 2007, and December 31, 2021. Therapeutic value ratings were obtained from national health authorities in Germany, France, and Canada. MAIN OUTCOMES AND MEASURES: Descriptive statistics were used to assess the proportion of accelerated approvals and conditional marketing authorizations overall and for cancer vs noncancer indications rated as having high added therapeutic value. RESULTS: The cohort included 146 drug indications (94 first indications, 52 supplemental indications) in the US and 58 (all first indications) in the EU. Most drugs were approved for cancer (122 [83.6%] in the US; 40 [69.0%] in the EU). Therapeutic value ratings were available for 90 drug indications (61.6%) in the US and 56 (96.6%) in the EU. Overall, 35 drug indications granted accelerated approval (38.9%) and 21 granted conditional marketing authorization (37.5%) had high added therapeutic value in the US and EU, respectively, at the time of approval. The proportions of indications rated as having high added therapeutic value were 36.0% (27 of 75) for cancer vs 53.3% (8 of 15) for noncancer indications in the US and 30.8% (12 of 39) for cancer vs 52.9% (9 of 17) for noncancer indications in the EU. CONCLUSIONS AND RELEVANCE: In this cohort study, among new drug indications approved through the accelerated approval or conditional marketing authorization pathways in the US and Europe from 2007 to 2021, 38.9% and 37.5%, respectively, demonstrated high therapeutic value. A substantially lower proportion of cancer indications than noncancer indications were rated as having high therapeutic value. Policy makers and regulators should increase enforcement of timely postapproval study completion for drugs qualifying for these pathways

Therapeutic value of first versus supplemental indications of drugs in US and Europe (2011-20): retrospective cohort study

Objective To analyze the therapeutic value of supplemental indications compared with first indications for drugs approved in the US and Europe. Design Retrospective cohort study. Setting New and supplemental indications approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) between 2011 and 2020. Main outcome measures Proportion of first and supplemental indications rated as having high therapeutic value using ratings from the French and German national, independent health authorities. Results The cohort study included 124 first and 335 supplemental indications approved by the FDA and 88 first and 215 supplemental indications approved by the EMA between 2011 and 2020; the largest subset was for cancer disorders. Therapeutic ratings were available for 107 (86%) first and 179 (53%) supplemental indications in the US and for 87 (99%) first and 184 (86%) supplemental indications in Europe. Among FDA approved indications with available ratings, 41% (44/107) had high therapeutic value ratings for first indications compared with 34% (61/179) for supplemental indications. In Europe, 47% (41/87) of first and 36% (67/184) of supplemental indications had high therapeutic value ratings. Among FDA approvals, when the sample was restricted to the first three approved indications, second indication approvals were 36% less likely to have a high value rating (relative ratio 0.64, 95% confidence interval 0.43 to 0.96) and third indication approvals were 45% less likely (0.55, 0.29 to 1.01) compared with the first indication approval. Similar findings were observed for Europe and when weighting by the inverse number of indications for each drug. Conclusions The proportion of supplemental indications rated as having high therapeutic value was substantially lower than for first indications. When first or supplemental indications do not offer added therapeutic value over other available treatments, that information should be clearly communicated to patients and physicians and reflected in the price of the drugs