Premature discontinuation of clinical trial for reasons not related to efficacy, safety, or feasibility ?/font> Commentary: Early discontinuation violates Helsinki principles. Michel Li鑦re, Jo雔 M閚ard, Eric Bruckert, Jo雔 Cogneau, Fran鏾is Delahaye, Philippe Giral, Eran Leitersdorf, G閞ald Luc, Luis Masana, Philippe Moulin, Philippe Passa, Denis Pouchain, G閞ard Siest, and K Boyd. BMJ 2001; 322: 603-606.
Responsibilities of sponsors are limited in premature discontinuation of trials. Richard Ashcroft. BMJ 2001; 323: 53.
Did the authors discard outliers?
You should be skeptical of any study that removes outliers. Inappropriate removal of outliers can seriously bias the study results.
Sometimes the outliers are more interesting than the bulk of the data themselves. You may gain more insight by trying to uncover the cause of an outlying observation than you would by examining the relatively small effects that occur with the rest of the data.
It is generally a bad idea to remove data points on the basis of their data values alone. If an investigation of an outlier leads to a discovery of a typing error or the inclusion of a subject who did not meet the pre-specified inclusion criteria, then correction or removal of the outlier is appropriate.
If there is no such justification, then the best solution is to leave the outlier alone. Another alternative is reporting data analysis results both with and without the outlier.
An example of inappropriate outlier deletion.
The NASA web site has an interesting example of outlier deletion. Researchers in the 1980s first published information about the hole in the ozone layer above Antarctica. These researchers were nervous because the results from the British Antarctic survey did not match results from earlier years taken by an American satellite. The authors discovered, however, that the American satellite had a computer filter built in that automatically removed any large sudden changes in ozone concentration which it considered as instrument errors. When this filter was removed, the authors were able to trace the development of the ozone hole all the way back to 1976.
Further details about the history of the ozone hole can be found at the NASA web site.
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Summary - Was there a plan?
The presence of a plan developed before data collection and analysis adds to the quality of a publication.
2.1 Did the research have a narrow focus? A large number of comparisons limits the amount of evidence that you can place on any single conclusion. Results from a limited number of planned comparisons are considered more authoritative.
2.2 Did the authors deviate from the plan? While minor deviations are expected, be cautious about major deviations from the research plan, such as developing new exclusion criteria during the course of the study. In particular, removing outliers without a sound scientific reason is dangerous.
