Thursday, July 17, 2008

The heavy burden of the modern clinical trial protocols

A recent article by Mr Getz in Applied Clinical Trials elaborated the heavy burden of protocol design in modern clinical trials. The clinical trial design become more and more complicated, requiring more study procedures, collecting more items. More complex and demanding protocols are hurting clinical trial performance and success.

I absolutely agree with his assessment. I can even add that the protocol design may also require more blood draws from the participants for hematology, chemistry, viral testing, biomarkers, pharmacokinetics, pharmacogenetics,… In some studies, patients may be exposed to more radio material exposures than ever. I even heard that a sponsor provided a comprehensive protocol with adaptive study design with many pages of appendices to describe how Bayesian algorithms are applied. We can imagine the reaction from investigator, CRA, even CRO statisticians. I don’t know how the investigator can understand these Bayesian algorithms. One question that needs to be answered is the target of the study protocol: is it for investigators? For regulatory authorities? For IRBs? For CRAs? Or for all of them?

Everything has a balance. Eventually we will get to a point that a too complex and too demanding protocol may actual hurt the study from every aspect in terms of the cost, resource, patient enrollment, data quality, generalization of the study results,…

Who to blame? I can think of the followings:
Regulatory requirement is getting tighter and tighter.
The sponsor is getting more conservative
The sponsor is trying to collect as much information as they can with no distinguishing of the items that are really necessary and the items that is merely nice to have.
Key opinion leaders are often asking for additional items to be added to the protocol for their own interest.

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