Medical Affairs as normally responsible for managing Investigator Initiated Trials and support of Global Company Sponsored research often are expected to take ownership for local registration trial design and following medical overview. This is not a rutine job for a Medical Advisors who often are not qualified for cinical design development and research management. At the same time clinical trial managers will not be assigned to do that because of their project dedicated and unflexible roles. Outsourcing clinical trial design intellingence is not a good idea as anyway manufaturer representatives will have to bridge the gap between stakeholder expectations and clinical project. Thus Medical Advisors are most suitable experts for local trial design development. The critical step before finilizing a study design is planning a pilot study. Pilot studies receive little or no attention in scientific research training or textbooks, that is why these considerations addressing Medical Advisors responsible for local trial design might be useful.
1. Identify the full scale trial objectives and procedures before designing a pilot study.
After you will clearly understand what steps you want to take place in the main study, you will be able identify what exactly to test in the pilot study. You may want to preliminary assess time, budget, recruitment or retention rates, etc. Also you may assess potential human and data optimization problems such as personnel and data management issues.
2. Be very clear about why do you need to conduct the pilot research.
Whether or not a study is a pilot, depends on its objectives. A pilot study should only be conducted if the results will be informative for the main study. Studies conducted for the false reasons may result in findings of limited utility, which would be a waste of the researchers’ and participants’ efforts. Among the false reasons there may be the folowing
– I have funding for 10 patients only;
– I have limited funding;
– My boss told me to do it as a pilot.
Besides quite often the emphasis is wrongly placed on statistical significance, not on feasibility – which in fact is the main focus of the pilot study.
3. Avoid using pilot trials to estimate treatment effects.
This can be dangerous as such estimates may be unrealistic or biased because of the limited sample sizes. Therefore if not used cautiously, results of pilot studies can potentially mislead sample size or power calculations, particularly if the pilot study was done to see if there is likely to be a treatment effect in the main study.
4. Establish the criteria for success of a pilot study.
The criteria should be based on the primary feasibility objective. These will provide the basis for interpreting the results of the pilot study and determining whether it is feasible to proceed to the main study. In general, the outcomes of a pilot study can be one of the following:
– main study not feasible – then stop;
– feasible with modifications – then continue, but modify protocol;
– feasible with close monitoring – then continue without modifications, but monitor closely;
– feasible as is – then continue without modifications.
For each of these scenarios you will have to create clear success criteria based on the feasibility outcomes – such as recruitment rates, consent rates, completion rates, variance estimates, etc.
5. Get the statistician involved.
Whereas Medical Advisors are not qualified in medical statistics this probably is a make-or-break for good study proposal. Statistician will help you elaborate the statistical methods for the analysis of primary and secondary feasibility outcomes.
6. Mind the sample size calculation.
In many cases pilot studies are conducted to generate data for sample size calculations. It is important that the sample for a pilot is representative of the target study population. It should also be based on the same inclusion/exclusion criteria as the main study. A pilot study should be large enough to provide useful information about the aspects that are being assessed for feasibility. Though the obtained data should be used with caution, as results from pilot studies can potentially mislead sample size calculations. You have to consider supplementing the information with qualitative discussions with clinicians.
7. You will have to publish results of the pilot study.
Any attempt should be published to provide medical community with information about feasibility to save resources being unnecessarily spent on studies that may not be feasible. Further, having such information can help researchers to avoid duplication of efforts in assessing feasibility.
8. Learn the basics of pilot study design.
Actually this is the key recommendation that I can provide you with. Lack of specific knowledge often make Medical Advisors bog down in research projects for many months without any progress. Though you will agree that there is no rocket science in designing pilot research when you read the articles that I’m referring to below.
1. Altman et al. Why do a pilot study? 2006
2. Friedman. Commentary: Why we should report results from clinical trial pilot studies Trials 2013, 14:14
3. Lancaster et al. Design and analysis of pilot studies: recommendations for good practice. Journal of Evaluation in Clinical Practice, 10, 2, 307–312
4. Thabane et al. A tutorial on pilot studies: the what, why and how. BMC Medical Research Methodology 2010, 10:1
Written by Dr. Alexander Tolmachev