Re-importation of pharmaceuticals may be unsafe: Lessons learned from the RADAR assessment of erythropoietin (EPO)-associated pure red cell aplasia (PRCA)
Bibliographic record
Abstract
2512 Background: Recombinant human erythropoietin (EPO) has been a breakthrough in cancer- and renal insufficiency-associated anemia since 1988. Antibody-mediated PRCA is a rare, serious toxicity characterized by severe anemia and neutralizing antibodies to EPO. Methods: The Research on Adverse Drug events And Reports (RADAR) project reviewed all suspected (n=448) and antibody-confirmed cases of PRCA reported worldwide from 1988 to Oct 2003. Results: Among 208 confirmed cases, median age was 66 (range, 14–86), male to female ratio was 2.4:1, median time from EPO initiation to PRCA suspicion was 9.4 months, and reports varied according to geography [Europe (58%), Asia (19%), Canada (13%), Australia (7%), and USA (3%)]; type of EPO used (EPO alpha alone, 81% and EPO alpha plus EPO beta, 16%); administration route (subcutaneous 97%); and year {incidence: pre-1998, 3 cases per million patient-years (MPY) and post-1998 [Australia (64 MPY), France (48 MPY), England (57 MPY), Canada (46 MPY), Spain (37 MPY), Italy (8 MPY), and Germany (7 MPY)]. 97% of cases were associated with Eprex brands. Reporting according to 4 milestones was evaluated: FDA approval in 1988 to Human Serum Albumin (HSA) removal from Eprex in Europe and Canada (1998; T1); from HSA removal to the first warning about PRCA from its manufacturer in 2001 (T2); to the second sponsor warning recommending a change from SC to IV administration in 2002 (T3), to the packet insert for Eprex brands of EPO contraindicating SC use for renal patients (T4), to Oct 2003 (T5), with variations according to country. In the more recent time periods, Canada had the highest incidence. Conclusions: EPO-associated PRCA remains an international concern, especially in Canada. Re-importation of Eprex products from Canada may allow for this severe complication to occur in the U.S. No significant financial relationships to disclose.
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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 | 0.022 | 0.072 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.004 | 0.005 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".