61 Phase 2 Clinical trial success: Association with statistical decision-making in preceding rodent experiments
Objectives/Goals: In neurological animal research, statistical misapplication may lead to overoptimism in a therapy’s potential for successful translation. This pilot study investigated whether human clinical trials that fail have higher prevalence of statistical misapplication in preceding animal e...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2025-04-01
|
| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124007404/type/journal_article |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850097906466422784 |
|---|---|
| author | Olivia Hogue Megan Zelinsky Claire Sonneborn Mary A Dolanksy Nancy A Obuchowski Kenneth B Baker Jill S. Barnholtz-Sloan |
| author_facet | Olivia Hogue Megan Zelinsky Claire Sonneborn Mary A Dolanksy Nancy A Obuchowski Kenneth B Baker Jill S. Barnholtz-Sloan |
| author_sort | Olivia Hogue |
| collection | DOAJ |
| description | Objectives/Goals: In neurological animal research, statistical misapplication may lead to overoptimism in a therapy’s potential for successful translation. This pilot study investigated whether human clinical trials that fail have higher prevalence of statistical misapplication in preceding animal experiments, compared to human trials that succeed. Methods/Study Population: Phase 2 clinical trials for 3 neurological conditions were identified on ClinicalTrials.gov and classified as successful or failed based on advancement to Phase 3 and/or preplanned efficacy test results. PRISMA guideline methods were used to systematically search for preclinical animal experiments (same indication and intervention) preceding the start of the human trial. Data were gathered from animal articles by collectors blinded to human trial outcome and included items describing reporting transparency, experimental design and sample sizes, and statistical tests applied. Statistical mistakes were coded based on mismatch between test and design. Rates of mistakes were compared between articles preceding successful and non-successful human trials using weighted point estimates and 95% confidence interval. Results/Anticipated Results: The final sample included 24 trials (16 successful) and 70 associated animal studies. Transparency was poor, with infrequent reporting of group allocation method (39%), sample sizes adequate to evaluate attrition (Discussion/Significance of Impact: Statistical misapplication is common in animal research, and this pilot study has demonstrated that preclinical statistical mistakes may indeed occur more frequently prior to failed human trials. Mistakes and lack of transparency may lead to overoptimism in preclinical experimental findings, with consequences for subsequent human translation. |
| format | Article |
| id | doaj-art-df1ed78e4bf543be9c068390f6a3f67f |
| institution | DOAJ |
| issn | 2059-8661 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj-art-df1ed78e4bf543be9c068390f6a3f67f2025-08-20T02:40:51ZengCambridge University PressJournal of Clinical and Translational Science2059-86612025-04-019191910.1017/cts.2024.74061 Phase 2 Clinical trial success: Association with statistical decision-making in preceding rodent experimentsOlivia Hogue0Megan Zelinsky1Claire Sonneborn2Mary A Dolanksy3Nancy A Obuchowski4Kenneth B Baker5Jill S. Barnholtz-Sloan6Cleveland ClinicCleveland ClinicCleveland ClinicCase Western Reserve UniversityCleveland ClinicCleveland ClinicNational Institutes of HealthObjectives/Goals: In neurological animal research, statistical misapplication may lead to overoptimism in a therapy’s potential for successful translation. This pilot study investigated whether human clinical trials that fail have higher prevalence of statistical misapplication in preceding animal experiments, compared to human trials that succeed. Methods/Study Population: Phase 2 clinical trials for 3 neurological conditions were identified on ClinicalTrials.gov and classified as successful or failed based on advancement to Phase 3 and/or preplanned efficacy test results. PRISMA guideline methods were used to systematically search for preclinical animal experiments (same indication and intervention) preceding the start of the human trial. Data were gathered from animal articles by collectors blinded to human trial outcome and included items describing reporting transparency, experimental design and sample sizes, and statistical tests applied. Statistical mistakes were coded based on mismatch between test and design. Rates of mistakes were compared between articles preceding successful and non-successful human trials using weighted point estimates and 95% confidence interval. Results/Anticipated Results: The final sample included 24 trials (16 successful) and 70 associated animal studies. Transparency was poor, with infrequent reporting of group allocation method (39%), sample sizes adequate to evaluate attrition (Discussion/Significance of Impact: Statistical misapplication is common in animal research, and this pilot study has demonstrated that preclinical statistical mistakes may indeed occur more frequently prior to failed human trials. Mistakes and lack of transparency may lead to overoptimism in preclinical experimental findings, with consequences for subsequent human translation.https://www.cambridge.org/core/product/identifier/S2059866124007404/type/journal_article |
| spellingShingle | Olivia Hogue Megan Zelinsky Claire Sonneborn Mary A Dolanksy Nancy A Obuchowski Kenneth B Baker Jill S. Barnholtz-Sloan 61 Phase 2 Clinical trial success: Association with statistical decision-making in preceding rodent experiments Journal of Clinical and Translational Science |
| title | 61 Phase 2 Clinical trial success: Association with statistical decision-making in preceding rodent experiments |
| title_full | 61 Phase 2 Clinical trial success: Association with statistical decision-making in preceding rodent experiments |
| title_fullStr | 61 Phase 2 Clinical trial success: Association with statistical decision-making in preceding rodent experiments |
| title_full_unstemmed | 61 Phase 2 Clinical trial success: Association with statistical decision-making in preceding rodent experiments |
| title_short | 61 Phase 2 Clinical trial success: Association with statistical decision-making in preceding rodent experiments |
| title_sort | 61 phase 2 clinical trial success association with statistical decision making in preceding rodent experiments |
| url | https://www.cambridge.org/core/product/identifier/S2059866124007404/type/journal_article |
| work_keys_str_mv | AT oliviahogue 61phase2clinicaltrialsuccessassociationwithstatisticaldecisionmakinginprecedingrodentexperiments AT meganzelinsky 61phase2clinicaltrialsuccessassociationwithstatisticaldecisionmakinginprecedingrodentexperiments AT clairesonneborn 61phase2clinicaltrialsuccessassociationwithstatisticaldecisionmakinginprecedingrodentexperiments AT maryadolanksy 61phase2clinicaltrialsuccessassociationwithstatisticaldecisionmakinginprecedingrodentexperiments AT nancyaobuchowski 61phase2clinicaltrialsuccessassociationwithstatisticaldecisionmakinginprecedingrodentexperiments AT kennethbbaker 61phase2clinicaltrialsuccessassociationwithstatisticaldecisionmakinginprecedingrodentexperiments AT jillsbarnholtzsloan 61phase2clinicaltrialsuccessassociationwithstatisticaldecisionmakinginprecedingrodentexperiments |