Added benefit and revenues of oncology drugs approved by the European Medicines Agency between 1995 and 2020: retrospective cohort study

Abstract

Objectives: To evaluate the added benefit and revenues of oncology drugs, explore their association, and investigate potential discrepancies between added benefit and revenues across different approval pathways of the European Medicines Agency (EMA).

Design: Retrospective cohort study.

Setting: Oncology drugs and their indications approved by the EMA between 1995 and 2020.

Main outcome measures: Added benefit was evaluated using ratings published by seven organisations: health technology assessment agencies from the United States, France, Germany, and Italy, two medical oncology societies, and a drug bulletin. All retrieved ratings were recategorised using a four point ranking scale to indicate negative or non-quantifiable, minor, substantial, or major added benefit. Revenue data were extracted from publicly available financial reports and compared with published estimates of research and development (R&D) costs. Finally, the association between added benefit and revenue was evaluated. All analyses were performed within the overall study cohort, and within subgroups based on the EMA approval pathway: standard marketing authorisation, conditional marketing authorisation, and authorisation under exceptional circumstances.

Results: 131 oncology drugs with 166 indications were evaluated for their added benefit by at least one organisation within the required timeframe, yielding a total of 458 added benefit ratings; 189 (41%) were negative or non-quantifiable. The median time to offset the median R&D costs ($684m, £535m, €602m, adjusted to 2020 values) was three years; 50 of 55 (91%) drugs recovered these costs within eight years. Drugs with higher added benefit ratings generally had greater revenues. Negative or non-quantifiable added benefit ratings were more frequent for conditional marketing authorisations and authorisations under exceptional circumstances than for standard marketing authorisations (relative risk 1.53, 95% confidence interval 1.23 to 1.89). Conditional marketing authorisations generated lower revenues and took longer to offset R&D costs than standard marketing authorisations (four years compared with three years).

Conclusions: While revenues seem to align with added benefit, most oncology drugs recover R&D costs within a few years despite providing little added benefit. This is particularly true for drugs approved through conditional marketing authorisations, which inherently appear to lack comprehensive evidence. Policy makers should evaluate whether current regulatory and reimbursement incentives effectively promote development of the most effective drugs for patients with the greatest needs.

Fig 1

Flowchart of inclusion process leading to three final study cohorts. Subgroup analyses were performed with SMAs, CMAs, and AECs in added benefit cohort, and with SMAs and CMAs in revenue cohort and combined cohort. AEC, authorisation under exceptional circumstances; ATC, Anatomical Therapeutic Chemical; CMA, conditional marketing authorisation; EMA, European Medicines Agency; EPAR, European public assessment report; SMA, standard marketing authorisation

Fig 2

Median cumulative revenues between years 1 and 8 after market entry. Dashed lines indicate estimated research and development (R&D) costs of a single oncology drug, with median of $684m (range $166m to $2060m; $1=£0.782, €0.88, adjusted to 2020 values). Number of drugs for which follow-up data were available ranged from 109 in first year to 55 in eighth year of study period

Fig 3

Upper panel: proportions of drugs that offset median estimated research and development (R&D) costs of $684m over time ($1=£0.782, €0.88, adjusted to 2020 values). Number of drugs for which follow-up data were available ranged from 109 in first year to 55 in eighth year of study period. Lower panel: sensitivity analysis accounting for drugs with missing revenue data owing to selective disclosure of major or best selling products. Number of minor or less successful drugs ranged from 14 in first year to six in eighth year of study period

Fig 4

Boxplots (median, maximum, minimum, upper and lower quartile) showing cumulative revenues three years after market entry for oncology drugs that received ratings of negative or non-quantifiable (n=50), minor (n=32), substantial (n=38), or major (n=29) added benefit (149 added benefit ratings for 43 drugs). Dots represent outliers. $1=£0.782, €0.88, adjusted to 2020 values

Fig 5

Median cumulative revenues of oncology drugs approved through standard marketing authorisations (SMAs) and conditional marketing authorisations (CMAs) from years 1 to 8 after market entry. Dashed lines indicate estimated research and development (R&D) costs of a single oncology drug with median of $684m (range $166m to $2060m; $1=£0.782, €0.88, adjusted to 2020 values). Number of drugs in each year ranged from 77 for SMAs and 26 for CMAs in first year to 41 for SMAs and nine for CMAs in eighth year of study period because not all included drugs had been on the market for full study period