End of the Double-Blind Randomized Control Trial?

double blind randomized control trialThe short answer is probably not – the randomized control trial is safe for now.  The longer answer when it comes to exploring molecular targets in oncology we may need to rethink the double-blind randomized control trial.

Since current methods to assess potential cancer treatments are cumbersome, expensive, and often inaccurate, can we develop other methods to rapidly test interventions for cancer treatment or prevention?

Advances in 3-dimensional cell culture suggest that multiple cell types can be assembled in vitro and that engineered tissues often mimic many of the features of human organs. If systems can be developed that mimic the natural environment of tumors, perhaps these models will recapitulate drug action. It also seems possible that complex cell-free systems could be developed that would recapitulate at least some features of drug responses. Since it seems unlikely that any one new system will serve as an accurate model for all tumors, each may need to be tuned to the particular features of a particular tumor type or subtype.
– NCI PQ 17*

*NCI provacative questions

Targeted Antibodies and Proteins are all Around Us

One counter to the argument of alternative research methods for these agents is that many drugs that fit this bill already have indications based on randomized control trials.  A quick search plus no more than a minute of head scratching brings over thirty to mind.

  • alemtuzumab
  • alitretinoin
  • bevacizumab
  • bexarotene
  • bortezomib
  • brentuximab
  • cetuximab
  • crizotinib
  • dasatinib
  • denileukin diftitox
  • erlotinib
  • everolimus
  • gefitinib
  • ibritumomab
  • imatinib
  • ipilimumab
  • lapatinib
  • nilotinib
  • ofatumumab
  • panitumumab
  • pazopanib
  • pertuzumab
  • pralatrexate
  • rituximab
  • romidepsin
  • sorafenib
  • sunitinib
  • temsirolimus
  • tositumomab
  • trastuzumab
  • tretinoin
  • vandetanib
  • vemurafenib
  • vorinostat

They Survived the Randomized Control Trial …

This begs the question why do we need alternative or supplemental methods of investigation?  Not every, in fact few, cancers are caused by a single bcr-abl-like mutation.  The more common scenario is something like lung cancer whose genome appears is the circus plot below.

Pleasance et al. Nature 463, 184-190 (14 January 2010).

Driver’s Seat

Once a driver mutation is identified in animal models, it will be increasingly difficult develop targeted therapies if the rate of mutation in the tumor is small.  In the past, it was cost prohibitive to sequence many different tumors looking for these less common mutations.  Times are changing and our technology is likely outpacing our investigative model.

Trial Proposals

I would love to see if anyone has an alternative to our standard trials.  For now, randomized control trials are safe but the new paradigm may be coming.  We just don’t know what it looks like yet.


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