The Right To Try Is Not
the Answer. Greater Access to Less Rigid Trials Is

By

Leonard Zwelling

http://www.wsj.com/articles/winning-the-right-to-save-your-own-life-1448574113

         The Wall Street
Journal
on Friday, November 27 published an op-ed by Darcy Olsen of the
Goldwater Institute advocating greater access of patients to on-demand, potentially
life-saving, but yet to be approved therapies outside the setting of a clinical
trial.  This is the so-called “right to
try” and it has been passed in 24 states. While emotionally this seems
satisfying as a solution, it isn’t because it does not directly address the
reason access to these drugs is so restricted.

         First, these drugs are all in some sort of clinical trial OR
have completed trials and are awaiting an FDA ruling for approval for general
commercial prescribing. In the first instance, the entry criteria for trials
must be widened to allow greater accrual and in the second, compassionate
approval should be both simple and fast.

         Second, most of these drugs are very expensive. Once the
trial data are collected and are waiting an FDA ruling, the drug companies
cannot be expected to foot the bill for the drug. Nor should an insurance
company be expected to carry the full price. Either the patient must pay the
bill or the drug company must be allowed to collect its cost only from insurers,
but only when the drug is under consideration for approval by the FDA, not in
the middle of phase 2 trials.

         Third, as genomics is teaching us, it is possible that every
patient with cancer may harbor a tumor unlike anyone else’s and the genetic
constituency of a cancer may even vary from site to site within a single
patient. Rigid entry criteria for clinical trials that are written to make the
drug look good, but which also serve to bar the entry of many patients into the
trial, are also impositions to “right to try.” Entry criteria should be
loosened not tightened.

         It is likely that genomics will reveal that every cancer
patient is an N of one, that is unique to all others. The bundling of
putatively similar patients into trial cohorts may have seen its heyday. The
best solution is to open access to trials widely, collect as much data as
possible and review it often and design the trials using Baysian statistics to
allow frequent modifications to discover the best way and the best
circumstances to use these new agents.

         Of course, the Olsen column caught my eye because the example
she uses to illustrate the FDA’s nonsensical approach to protecting the American
people is the drug MTP developed by none other than the BW and Paul Meyers at
Sloan Kettering based on the basic research of Josh Fidler. There is nothing
unique about MTP though. It is a definite but incremental improvement in the
treatment of osteosarcoma and is probably similar to a host of other new agents
in adding something to the treatment of cancer. Surely the manner in which to
employ these drugs would be far more rapidly understood if more people had
access to them, not fewer. The current system of drug approval forces the drug
industry to design trials most likely to show efficacy. If the FDA would get
its act together and realize that people are not cloned mice and their cancers
aren’t cloned either, the agency would realize that giving new drugs to more
people under conditions in which more data can be collected is a good thing.

         If genomics has done anything, it has made us realize that
the anatomic and pathologic criteria by which we have characterized cancer for
the past 100 years is inaccurate and outdated. It is every bit as likely that a
colon cancer and a lung cancer may have more in common genetically than two
different lung cancers. It is going to take medicine a while to sort all of
this out, but the regulatory agencies must keep up if the public is to gain the
most from its tax dollars distributed through the NIH. The current system is
antiquated and needs replacing. Now that the FDA will have a new leader in Rob
Califf, it is time to make those changes.

         The right to try is just a free for all and will lead to the
loss of a great deal of valuable data because the data simply won’t be
collected. This is a terrible idea. Instead, let’s increase access to far more
flexibly designed trials and collect all the data on anyone willing to
participate. It gives us the greatest chance to make progress and isn’t that
the idea?   

Leonard Zwelling