Discontinued development programmes as evidence
What can be concluded from a development programme that was discontinued, and how should the Institute record it?
§1Abstract
§1.1Review question
What can be concluded from a development programme that was discontinued, and how should the Institute record it?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Compounds whose clinical development was terminated. |
| Intervention | Not applicable. |
| Comparator | Not applicable. |
| Outcomes | The reason for discontinuation as recorded; the availability of the underlying data; the treatment of the compound in unregulated supply after discontinuation. |
§1.3Method in brief
A review whose unit of analysis is a study characteristic rather than a treatment effect. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 13 January 2024 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.
§1.4Conclusion
Moderate certainty evidence supports the position that a discontinued programme is informative and is frequently the most informative evidence available for a compound. A programme discontinued for futility after an adequately powered trial provides evidence of absence of the effect studied. A programme discontinued for tolerability provides evidence about the achievable dose. A programme discontinued for commercial reasons provides neither, and the distinction is recorded on each monograph. The Institute records that several compounds continue to be supplied for the very indication in which their own development programme failed.
The conclusion rests on 9 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: Discontinued development programmes as evidence received 3 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.