The Problem with Clinical Trials

While the clinical trial I participated in probably saved my life, the truth remains that clinical trials are very poorly run often using drugs known to be ineffective as benchmarks, costly to PATIENTS (in time, treasure, and lives at risk), fail to focus on the individual, lack transparency, frequently apply results in a rigid, pseudo-scientific manner by drug companies and the FDA alike, and the role of the NIH produces more questions than answers.  Opdivo's latest approval is one more example of both the wonder and sad realities of FDA approvals and Big Pharma.

Clinical trials are designed to answer questions about the effectiveness and safety of drugs.  However, trials...set up by medical researchers, institutions, and pharma....utilize rigid old-school statistical methodology that fails to allow a comprehensive look at data from multiple trials and more often than not, pits older, clearly ineffective drugs against new, obviously superior ones.  Rarely are top shelf drugs placed one against the other.  In melanoma world, interferon and dacarbazine have been the benchmarks against which everything from ipi to anti-PD1 to BRAF inhibitors have been placed.  Why?  In very preliminary testing all three of those drugs/categories were superior by miles.  This approach wastes time.  Time in which real people suffer and die.  Meanwhile, the FDA takes clinical trial design as a literal reflection of the real world.  Obviously, it is not.  And all of this begs the question:  Who are these trials designed to help?  Patients?  Or Big Pharma?

For instance, in the latest Opdivo approval, only patients with BRAF wild type mutation can utilize the drug as a first line option.  Folks with BRAF positive lesions are still relegated to trying ipi and failing, then BRAF inhibitors and failing, before advancing to Opdivo.  Why?  Multiple studies clearly demonstrate equal effectiveness of the anti-PD1 drugs no matter BRAF status.  But, the FDA's commitment to basing approvals entirely upon the trial at hand dictates this "logic".  The trial upon which this approval was based used only BRAF wild type patients...so that is how Opdivo was approved.  All other concomitant trial results be damned.  So?  Does pharma set trials up this way so that older drugs must continue to be used?  So that coin for those treatments can continue to fill their coffers?  Now, will docs allow their patients to suffer through greater side effects and a decreased rate of success by prescribing ipi first, rather than trying one of the anti-PD1 products?  Will insurance companies prefer to pay for a drug that helps fewer patients and causes more complications that they will also have to put out money to take care of, only to have to pay for the NEXT drug as well?  Time will tell.

The FDA's tunnel vision and literal interpretation of singular trial data one by one is the equivalent of this scenario:  Say a trial for a new drug to treat fractures is set up so that it allocates patients with left arm fractures to the test drug and those with a right arm fracture to an old one.  Miraculously, the folks given the new drug for their left arms were healed within days while those with right arm fractures derived no benefit from their drug.   The FDA approval comes out as:  This amazing fracture drug is now available!!!  BUT....only for folks with fractures to their left arms!  Pretty silly, right?  Yet, that is the system we currently embrace.  Obviously, when only one type of trial or circumstance of use is available for a drug in question, that is the way it should be approved.  However, when other data exists and common sense dictates what is good for the left arm is also good for the right, that information should figure into FDA approvals.  To do otherwise makes trial development look as though it was designed for niche marketing rather than improved patient health.  An argument can easily be made that the primary focus of clinical trials and FDA approvals seems to be to produce proprietary treatments for big profits rather than a cooperative effort to help as many individuals as possible.

Then we have the poor little rich pharma companies, complaining of, yet endlessly touting, their exorbitant research and development costs.  First of all, the figures touted are much inflated.  Numerous studies, including one recently out from Doctors Without Borders, dispute and provide clear evidence against Big Pharma's numbers.  Secondly, ratties (and their insurance companies) pay for much of the research.  Clinical trials are not free!!!  I paid for everything from scans to needles to tubing to lab to doctor visits to transportation to institutional charges for bed space and nursing services.  BMS provided the drug and a few "research labs"....period. Thirdly, Big Pharma receives federal support in the form of research grants from NIH that provide the nidus of basic discoveries.  And guess who pays for that?  YOU!!!  The taxpayer.  And fourth, Big Pharma makes humongous profits...billions of dollars.  Do wall street reports talk about major pharmaceutical companies operating in the red?  NO!!!  They report financial gains and incredible mergers like the recent purchase of  Allergan by Pfizer for 160 BILLION dollars!!!  See what I'm saying?????

In order to be of real benefit and utilized by science for the good of all, it is essential that data and information gleaned from clinical trials be transparent at all levels.  Patients need, deserve and have a right to their OWN information.  All clinical trial information should be readily available to all trial participants.  However, this is not how it works.  Doctors withhold information to protect themselves and sometimes under the erroneous assumption that they are protecting the patient. Pharma withholds information because they think they OWN it.  I have never been told, nor have any of the other ratties in my trial, the results of our PD-L1 testing.  This is important stuff.  The rattie needs to know anything that is learned about them.  It may impact later treatment options or choices they make. The data needs to be readily available for other researchers, too - even if they work for different organizations.  A different set of eyes may find patterns and trends not apparent to the initial investigators, thereby elevating what is 'known' to a new level.  Even failed or negative study results need to be available.  People died for it.  Think of the data you have learned in your own life experience.  I know I certainly learned as much from my failures as I did from my successes!!!  Yet, almost 50% of cancer trial data goes unpublished!!!  Here's a link to that report:  Almost 50% of results are NOT published - 2013
 
So, why is everything a secret? Trial information is proprietary so that Big Pharma can protect their market share and inflate their bottom line or the drug price.  It is proprietary in order for researchers and their institutions to protect future patent rights, potential material gains, both financial and in PR.  It is proprietary to produce big profits, promote careers, and effectively block cooperative efforts that would ultimately help as many individuals as possible at the least cost....in dollars as well as suffering.

The monolithic system in which current clinical trials operate, under the banner of "safety and science" while more often seeming to advance proprietary products for profits, needs to give way to the humanitarian system of creative thought, mutual aid, transparency, and the commitment to the individuals affected - each and every one.  Many will still suffer.  Some will die.  But in an open system, where reasonable drugs are used as comparators, ALL data is available for ALL to see (the good, the bad and the ugly) all of us....researchers, institutions, Big Pharma, and Ratties... will be doing their best for each other.

Wishing you all my best, Les....Rattie, Mom, sister, friend, Pediatric Provider, researcher, and Melanoma survivor for almost 13 years with great help from my dearest love and coauthor - B....Daddy, care giver, friend, Pediatrician, linguist, researcher.....with a combined 71 years between us, spent in the care of children and their families.