Saturday, May 2, 2015

What ALS Can Learn from the Cancer Experience: Bypassing Clinical Trials, A Cautionary Tale

Asian man in white lab coat working on an experiment.
Dr. Siddhartha Mukherjee’s, author of the book, The Emperor of all Maladies: A Biography of Cancer in the PBS Documentary said, “Medicine being the most humane science…sometimes scientists are caught doing inhumane things which is denying experimental drugs.  However, putting a drug on the market too early has had historically devastating events.” 

What Mukherjee is referring to is the consequences of releasing an experimental drug or treatment via Accerlated Access before Phase 3 clinical trials have been undertaken.  An example of this is the STAMP treatment for breast cancer in the 1980s and 1990s.

In 1983, Dr. Peters and Dr. Frei started breast cancer clinical trials on a new therapy previously shown to have some success at treating childhood leukemia, known as the Solid Tumor Autologous Marrow Program (STAMP).  STAMP involved extracting bone marrow from the participant and freezing it, then wiping out their cancer with extremely high doses of chemotherapy, and injecting the bone marrow back into the person so that the high-dose chemotherapy wouldn’t kill them.  Promising success in Phase 1 and 2 clinical trials with breast cancer patients encouraged women who could not participate in the trials to seek accelerated approval of the treatment.  Soon 30,000 some women received access to the experimental therapy between 1985 and 1998 at the cost of millions of dollars.  The study could not recruit people for the Phase 3 clinical trials because no one wanted to be in the control group.  About 1 in 5 women died from the treatment and it was later shown that the higher dose of chemotherapy was not any more successful than the lower doses in improving women’s survival.  And in fact there was a higher chance of death due to the bone marrow implants.  Those who did survive the procedure suffered long term cognitive problems such as short term memory loss.     
    
Some of you might still be asking yourselves, so what’s the big deal?  The women at least got a chance to try something?  The big deal is that an experimental treatment that has not gone through the full round of required clinical trials carries a higher risk of actually shortening the person’s life if not killing them.  Perhaps someone who is near the tail end of their disease is willing to take this risk, but what if you are someone who is early on in their disease?  By foregoing clinical trials you risk shortened lifespan, death, and the right to try other treatments that might become available.  That’s right, clinical trials have strict inclusion and exclusion criteria.  Meaning, in order for the researchers to know without a doubt that their treatment is having an effect, they cannot allow anyone into the trial that has taken other experimental drugs.  Moreover, what if a drug is approved for Accelerated Access and a large number of people start taking the drug and suddenly have major toxic reactions or die.  Even if this is unrelated to the treatment itself, such an event might trigger the FDA to remove the treatment from the market altogether…that’s it.  A possible beneficial treatment to some people with ALS will never reach them.        
  
I’m not saying we should not seek treatments through Accelerated Access period. I’m simply saying there is a time and place.  The U.S. FDA Evaluation team is in place to insure consumer safety.  If companies can satisfy their requirements that show scientifically that their treatment warrants Accelerated Access based on evidence that is safe and efficacious than this is a good thing.  If not, we should consider other options for treatments outside clinical trials such as Widespread and Group Expanded Access, which is politically more kosher with the U.S. FDA and doesn’t hinder the clinical trial process. 

On May 10, let’s ask our policy-makers to work with ALS advocates, pharmaceutical and biotechnology companies, the Centers for Medicare and Medicaid Services and the U.S. FDA to remove barriers for companies to offer Expanded Access to People with ALS.

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