Right to Try?

May 19, 2014

By Yoram Unguru, MD, MS, MA


Recently, the state of Colorado passed a bill known as “The Right to Try Act.”  The bill grew out of the desire to afford dying patients access to potentially beneficial experimental agents they otherwise would not be able to access through traditional channels.  Currently, three other states, Missouri, Louisiana, and Arizona are close to passing similar legislation.  As written, the bill provides terminally ill patients access to experimental agents that have successfully passed through phase I testing only.  While the intention of the Colorado bill is meritorious and highlights certain misgivings inherent in the current system, bypassing the current system through which drugs are evaluated is not unproblematic and necessitates proceeding with caution.



As drafted, the bill states that the use of an investigational agent is a decision to be made by the terminal patient and his/her physician.  Certainly, the initial decision to pursue an experimental agent should indeed be the patient’s along with the professional input of the appropriate treating physician; however, neglecting the FDA’s role in guaranteeing that drugs are safe and effective is inappropriate.


To fully appreciate the intent of the Colorado bill it is worth recalling that the intent of phase I testing is to evaluate a drug’s maximum tolerated dose, its safety, and its side effects as determined in testing of a small number of people.  Subsequent testing in phase II and phase III clinical trials is necessary to assure that drugs are effective, especially in larger numbers of patients.  This process can take years to complete and, for patients who are dying, often presents a significant and at times, insurmountable hurdle.


Just because an experimental drug may benefit one patient does not mean that it will necessarily benefit others.  In fact, it may result in greater harm.  In the early 1990s, early clinical trial evidence suggested that autologous bone marrow transplantation (auto-BMT) for treatment of patients with breast cancer was promising (patients’ own stem cells were harvested and then re-infused at a later time point, allowing for administration of additional cycles of intensive chemotherapy, which would otherwise have been impossible).  Before additional studies were conducted to prove the efficacy of auto-BMT for breast cancer, there was intense public demand for widespread use of auto-BMT, largely based on the argument that some patients did not have time to wait for full-scale trials to be completed.  Ultimately, auto-BMT proved unsuccessful.  Trial after trial showed no benefit to auto-BMT and these trials were unable to recreate the findings suggested by the original trial, which was subsequently determined to have been poorly designed.  Some patients who were treated with auto-BMT actually did much worse, including some who died.  Thus, what was meant as a compassionate step aimed to help those who were in the greatest need, vulnerable patients who understandably may be willing to try anything, backfired and had serious repercussions.


Presently, terminal patients interested in using a non-clinically proven agent have to petition the FDA through a program called compassionate use.  The FDA decides each petition on a case-by-case basis, and even when it finds in favor of patients, the process can take time. At heart, the Colorado bill remains a compassionate use program, the only difference is that it removes the FDA from the calculus.  However, patients and doctors still have to petition the drug company which is under no obligation to release the experimental drug.  In fact, companies may balk at doing so because it may compromise ongoing trials of the agent, may prove quite costly, and often, may not have an additional supply to offer for compassionate use.


Another concern is that by bypassing the existing approval process, some drugs that may not be safe and ready for widespread use, will suddenly have an avenue to be tried “free of charge,” that is, without fear of consequences.  Because the bill exempts drug companies from responsibility should a so-called “bad outcome” occur, some manufacturers might see this as a way to test their drugs in a way that they otherwise would not be able to.


Moreover, some companies might petition doctors to refer terminal and potentially desperate patients who may not be the ideal candidate for a particular drug.  One might also imagine doctors being offered certain incentives to do so.


The plight of terminal patients is a tragic one especially when an experimental agent that holds the promise for potential benefit is beyond their reach.  In such cases, one might imagine revamping certain aspects of clinical trials for terminally ill patients who have few, if any, meaningful options to extend their lives.  When a particular experimental agent has relatively few side effects and/or a significantly positive response, perhaps it makes sense to relax access.  Instead of randomizing patients as is typically practiced whereby one patient receives the experimental drug and one patient the control, we should consider allowing more patients to receive the experimental drug, say in a 2:1 or a 3:1 randomization.  Additionally, less stringent statistical end points and easier crossover to receive the experimental agent, once a drug begins to show promise, should also be considered.  Finally, these types of decisions should involve public discussion and comment.




UnguruYoram Unguru, MD, MS, MA, Division of Pediatric Hematology/Oncology, The Herman and Walter Samuelson Children’s Hospital at Sinai and Johns Hopkins Berman Institute of Bioethics

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