When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples
Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found tha...
| Main Authors: | , , , , |
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| Format: | Article |
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Multidisciplinary Digital Publishing Institute
2023
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| Online Access: | https://hdl.handle.net/1721.1/150888 |
| _version_ | 1811085418469261312 |
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| author | Scheim, David E. Aldous, Colleen Osimani, Barbara Fordham, Edmund J. Hoy, Wendy E. |
| author_facet | Scheim, David E. Aldous, Colleen Osimani, Barbara Fordham, Edmund J. Hoy, Wendy E. |
| author_sort | Scheim, David E. |
| collection | MIT |
| description | Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based upon ITT analysis, with only 42% of the intervention group actually undergoing the procedure. However, the study authors themselves concluded that the medical efficacy of that screening was a 50% reduction in colorectal cancer deaths among that 42% PP group. The second RCT found a ten-fold reduction in mortality for a COVID-19 treatment drug vs. placebo by PP analysis, but only a minor benefit by ITT analysis. The third RCT, conducted as an arm of the same platform trial as the second RCT, tested another COVID-19 treatment drug and reported no significant benefit by ITT analysis. Inconsistencies and irregularities in the reporting of protocol compliance for this study required consideration of PP outcomes for deaths and hospitalizations, yet the study coauthors refused to disclose them, instead directing inquiring scientists to a data repository which never held the study’s data. These three RCTs illustrate conditions under which PP outcomes may differ significantly from ITT outcomes and the need for data transparency when these reported or indicated discrepancies arise. |
| first_indexed | 2024-09-23T13:09:16Z |
| format | Article |
| id | mit-1721.1/150888 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:09:16Z |
| publishDate | 2023 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | mit-1721.1/1508882023-06-10T03:25:10Z When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples Scheim, David E. Aldous, Colleen Osimani, Barbara Fordham, Edmund J. Hoy, Wendy E. Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based upon ITT analysis, with only 42% of the intervention group actually undergoing the procedure. However, the study authors themselves concluded that the medical efficacy of that screening was a 50% reduction in colorectal cancer deaths among that 42% PP group. The second RCT found a ten-fold reduction in mortality for a COVID-19 treatment drug vs. placebo by PP analysis, but only a minor benefit by ITT analysis. The third RCT, conducted as an arm of the same platform trial as the second RCT, tested another COVID-19 treatment drug and reported no significant benefit by ITT analysis. Inconsistencies and irregularities in the reporting of protocol compliance for this study required consideration of PP outcomes for deaths and hospitalizations, yet the study coauthors refused to disclose them, instead directing inquiring scientists to a data repository which never held the study’s data. These three RCTs illustrate conditions under which PP outcomes may differ significantly from ITT outcomes and the need for data transparency when these reported or indicated discrepancies arise. 2023-06-09T15:02:51Z 2023-06-09T15:02:51Z 2023-05-23 2023-06-09T13:01:06Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/150888 Journal of Clinical Medicine 12 (11): 3625 (2023) PUBLISHER_CC http://dx.doi.org/10.3390/jcm12113625 Creative Commons Attribution application/pdf Multidisciplinary Digital Publishing Institute Multidisciplinary Digital Publishing Institute |
| spellingShingle | Scheim, David E. Aldous, Colleen Osimani, Barbara Fordham, Edmund J. Hoy, Wendy E. When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples |
| title | When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples |
| title_full | When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples |
| title_fullStr | When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples |
| title_full_unstemmed | When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples |
| title_short | When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples |
| title_sort | when characteristics of clinical trials require per protocol as well as intention to treat outcomes to draw reliable conclusions three examples |
| url | https://hdl.handle.net/1721.1/150888 |
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