This is somewhat of a regulatory question, rather than statistical question. But I assume that the readership of this community will be the most knowledgeable on this matter.
Is there any regulatory agency that actually documents submission of a statistical analysis plan (SAP) for clinical trials prior to the final clinical database lock and treatment unblinding?
What surprised me a bit is that there appears to be no obligation to actually submit a statistical analysis plan a priori. Could someone please tell me that I am incorrect about this and that a priori SAPs are always available to the public?
Here are some examples of rather vague suggestions:
ICH E9 Statistical Principles for Clinical Trials:
"The plan should be reviewed and possibly updated as a result of the blind review of the data and should be finalised before breaking the blind."
U.S. FDA, Guidance for Industry Developing Medical Imaging Drug and Biological Products, June 2004:
"We recommend that sponsors [...] submitted to the protocol before images have been collected."
Recently, a "positive" phase III trial result has been published for a disease in my area of expertise. However, the are several "red flags" in my opinion:
- Actual results are not reported
- Only mixed model for repeated measures (MMRM) estimates were reported, but it is rather unclear what co-variates were used for "adjustment" in the model [on clinicaltrials.gov, there is no mentioning of "adjustment" for co-variates]
- The outcome variable was transformed [on clinicaltrials.gov, there is mentioning of transformation of the outcome variable]
Having worked on natural history data for this disease before, it is obvious that one can easily find "significant" between-group differences by iterating across combinations of outcome transformations (no transformation, sqrt, log10) and co-variates combinations (age, gender, baseline lesion size). For obvious reasons, I suspected that a statistical analysis plan must be deposited somewhere a priori. However, the specific study did not publish the statistical analysis plan on clinicaltrials.gov.