Pocock boundary
Encyclopedia
The Pocock boundary is a method for determine whether 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 concept was introduced by the medical statistician Stuart Pocock
in 1977. The many reasons underlying when to stop a clinical trial for benefit were discussed in an editorial from his hand in 2005.
threshold for each interim analysis which guides the data monitoring committee on whether to stop the trial. The boundary used depends on the number of interim analyses.
The Pocock boundary is simple to use in that the p-value threshold is the same at each interim analysis. The disadvantages are that the number of interim analyses must be fixed at the start and it is not possible under this scheme to add analyses after the trial has started. Another disadvantage is that investigators and readers frequently do not understand how the p-values are reported: for example, if there are five interim analyses planned, but the trial is stopped after the third interim analysis because the p-value was 0.01, then the overall p-value for the trial is still reported as <0.05 and not as 0.01.
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
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...
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 concept was introduced by the medical statistician Stuart Pocock
Stuart Pocock
Stuart J. Pocock is a British medical statistician. He has been professor of medical statistics at the London School of Hygiene and Tropical Medicine since 1989. His research interests include statistical methods for the design, monitoring, analysis and reporting of randomized clinical trials...
in 1977. The many reasons underlying when to stop a clinical trial for benefit were discussed in an editorial from his hand in 2005.
Details
The Pocock boundary gives a p-valueP-value
In statistical significance testing, the p-value is the probability of obtaining a test statistic at least as extreme as the one that was actually observed, assuming that the null hypothesis is true. One often "rejects the null hypothesis" when the p-value is less than the significance level α ,...
threshold for each interim analysis which guides the data monitoring committee on whether to stop the trial. The boundary used depends on the number of interim analyses.
| Number of planned analyses | Interim analysis | p-value threshold |
|---|---|---|
| 2 | 1 | 0.0294 |
| 2 (final) | 0.0294 | |
| 3 | 1 | 0.0221 |
| 2 | 0.0221 | |
| 3 (final) | 0.0221 | |
| 4 | 1 | 0.0182 |
| 2 | 0.0182 | |
| 3 | 0.0182 | |
| 4 (final) | 0.0182 | |
| 5 | 1 | 0.0158 |
| 2 | 0.0158 | |
| 3 | 0.0158 | |
| 4 | 0.0158 | |
| 5 (final) | 0.0158 |
The Pocock boundary is simple to use in that the p-value threshold is the same at each interim analysis. The disadvantages are that the number of interim analyses must be fixed at the start and it is not possible under this scheme to add analyses after the trial has started. Another disadvantage is that investigators and readers frequently do not understand how the p-values are reported: for example, if there are five interim analyses planned, but the trial is stopped after the third interim analysis because the p-value was 0.01, then the overall p-value for the trial is still reported as <0.05 and not as 0.01.