Haybittle–Peto boundary
Encyclopedia
The Haybittle–Peto boundary is a rule for deciding when to stop a clinical trial
prematurely.
The typical clinical trial compares two groups of patients. One group are given a placebo
or conventional treatment, while the other group of patients are given the treatment that is being tested. The investigators running the clinical trial will wish to stop the trial early for ethical reasons if the treatment group clearly shows evidence of benefit. In other words, "when early results proved so promising it was no longer fair to keep patients on the older drugs for comparison, without giving them the opportunity to change."
The Haybittle–Peto boundary is one such stopping rule
, and it states that if an interim analysis shows a probability of less than 0.001 that the treatments are the same, then the trial should be stopped early. The final analysis is still evaluated at the normal level of significance (usually 0.05). The main advantage of the Haybittle–Peto boundary is that the same threshold is used at every interim analysis, unlike other the O'Brien–Fleming boundary, which changes at every analysis. Also, using the Haybittle–Peto boundary means that the final analysis is performed using a 0.05 level of significance as normal, which makes it easier for investigators and readers to understand. The main argument against the Haybittle–Peto boundary is that some investigators believe that the Haybittle–Peto boundary is too conservative and makes it too difficult to stop a trial.
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
prematurely.
The typical clinical trial compares two groups of patients. One group are given a placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
or conventional treatment, while the other group of patients are given the treatment that is being tested. The investigators running the clinical trial will wish to stop the trial early for ethical reasons if the treatment group clearly shows evidence of benefit. In other words, "when early results proved so promising it was no longer fair to keep patients on the older drugs for comparison, without giving them the opportunity to change."
The Haybittle–Peto boundary is one such stopping rule
Stopping rule
In probability theory, in particular in the study of stochastic processes, a stopping time is a specific type of “random time”....
, and it states that if an interim analysis shows a probability of less than 0.001 that the treatments are the same, then the trial should be stopped early. The final analysis is still evaluated at the normal level of significance (usually 0.05). The main advantage of the Haybittle–Peto boundary is that the same threshold is used at every interim analysis, unlike other the O'Brien–Fleming boundary, which changes at every analysis. Also, using the Haybittle–Peto boundary means that the final analysis is performed using a 0.05 level of significance as normal, which makes it easier for investigators and readers to understand. The main argument against the Haybittle–Peto boundary is that some investigators believe that the Haybittle–Peto boundary is too conservative and makes it too difficult to stop a trial.
| Number of planned analyses | Interim analysis | p-value threshold |
|---|---|---|
| 2 | 1 | 0.001 |
| 2 (final) | 0.05 | |
| 3 | 1 | 0.001 |
| 2 | 0.001 | |
| 3 (final) | 0.05 | |
| 4 | 1 | 0.001 |
| 2 | 0.001 | |
| 3 | 0.001 | |
| 4 (final) | 0.05 | |
| 5 | 1 | 0.001 |
| 2 | 0.001 | |
| 3 | 0.001 | |
| 4 | 0.001 | |
| 5 (final) | 0.05 |