Access to new therapies: FDA accelerated approvals and the corresponding Canadian regulatory and funding decisions.
Bibliographic record
Abstract
e19066 Background: Accelerated approval (AA) by the FDA enables earlier access to promising new therapies while evidence generation is ongoing. Health Canada (HC) has a similar process with a Notice of Compliance conditional (NOCc) before full approval (NOC). Canada implemented health technology assessment (HTA) for determination of funding through the pan Canadian Oncology Drug Review (pCODR) in 2011. This study evaluated timelines and decisions from AA approval to HC NOC/c to HTA approval and formulary listing. Methods: FDA AA malignant hematology and oncology approvals from Jan 1 2000-Dec 31 2019 were reviewed. HC decisions were reviewed to determine submission/approval status and dates of NOC/c. pCODR decisions were reviewed to determine submission/approval status and dates of decision. First date of provincial formulary listing was collected. Results: In the 20 year time frame, there were 97 AA by the FDA. Current FDA status: 48 full approval, 44 pending verification and 5 withdrawn. Of the 92 AA that remain approved, HC status: 44 received NOC, 24 NOCc, 24 were not submitted for review, 2 currently under review. Of the 5 AA that were withdrawn; 3 were submitted to HC and received NOC/c and all were subsequently withdrawn. From 2011, 31 of 45 HC approved indications were reviewed at pCODR: 17 received a positive recommendation conditional on cost-effectiveness, 9 not recommended, 3 withdrawn by company, 2 pending final decision. Of the 10 not recommended/withdrawn, 6 were subsequently re-submitted and approved. Time from AA to NOC/c was 9.4 m, time from NOC/c to pCODR decision 15.0 m and time from pCODR decision to first formulary listing 18.4 m. Conclusions: Despite significant timeline differences between AA and HC NOC/c all indications that received AA submitted to Canada were granted regulatory approval. Since 2011, 74% of HC approved therapies submitted to pCODR were recommended and added to formularies. Collaboration between FDA and HC, independent regulatory agencies, through innovative programs such as FDA Project Orbis, may improve time from AA to NOC/c. Stringent criteria for HTA recommendation results in lower approval rates however, provision of additional data at re-submission may enable subsequent approval and adoption of treatment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.020 | 0.089 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.003 | 0.004 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.007 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.004 | 0.004 |
| Insufficient payload (model declined to judge) | 0.029 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".