While watching and listening to the US president’s 2018 “State of the Union” address, I was surprised when he raised the issue of the plight of patients with untreatable terminal medical conditions. Notably, the US president has continued to raise this issue in most of his speeches. This has a major impact for me since I have been engaged in research to develop a treatment for untreatable terminal cancers.
The US president’s advocacy for the treatment of the terminally-ill should transcend political differences, and the President should be praised for raising this concern. Knowing that one is going to die in 1-3 years is a dreadful situation for the terminally-ill patient and his/her family members. These patients and families become desperate and hopeful for the possibility that a treatment and cure might be forthcoming. For these patients “Time Is Running Out! Time Is of The Utmost Importance!”
Despite this, “Delay…Delay…Delay!” is inherent in the process of clinical trials for FDA. Phase I studies generally take several months to assess the safety of a drug in a small number of healthy volunteers (20 to 100). It is not until phase II, that the treatment efficacy of the drug is assessed; which can last from several months to two years.
In recognition of this, The FDA provides the “Compassionate use” (Expanded Access) policy for the use of investigational drugs for the treatment of terminally-ill patients. The FDA requirements for “Compassionate use” are: “Patient has a serious disease or condition, or whose life is immediately threatened by their disease or condition; There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; Patient enrollment in a clinical trial is not possible; Potential patient benefit justifies the potential risks of treatment.”
However, getting access to not-yet-approved drugs through a “Compassionate use” request can be a long and challenging process. The patient’s physician must submit an application to the FDA asserting that the patient’s condition meets the requirements described above for “Compassionate use” of an investigational drug.
Additionally, the US president signed legislation that gives patients the “right to try” experimental drugs. This provides a terminally ill patient an option to try an experimental drug that has met the FDA requirement of being a safe drug for human use, but need not been shown to be therapeutically effective. This permits the terminally ill patients, who have exhausted all FDA-approved treatments, to proceed with an experimental treatment that could eliminate or improve their terminal condition.
Let’s consider the impact of the “right to try” legislation. For this, I will present some cancer cases with which I have been involved. Advanced metastatic prostate cancer results in ~30,000 deaths/year in the U.S., with a 5-year survival rate of ~30%. Following androgen ablation treatment, the metastasis progresses as untreatable terminal cancer and death generally in 2-5 years. Because of my published research on a potential treatment that aborts the malignancy, I regularly receive emails from terminal prostate cancer patients and their physicians who are desperate and want to employ this treatment.
Liver cancer accounts for about 28 000 cases/year with a 5-year survival is ~13% of which most death occurs within the first year following diagnosis. Pancreatic cancer accounts for ~44,000 new cases/year in the U.S., of which ~38,000 deaths (80%) will occur. The 5-year survival rate has remained at ~6% or less for the past 35 years. These are currently untreatable terminal cancers which qualify for patient treatment under the “right to try” requirements. It is evident that these terminally-ill patients will not survive under conditions that impose delays for access to potential treatment.
The conduct of clinical trials and the treatment of patients at university medical centers generally require the review and approval by an IRB (Internal Review Board). In addition to the FDA requirements, the IRB often requires additional conditions for the approval of a patient treatment regimen. This process often takes some months to obtain an IRB approval. My impression is that the issue of the treatment of terminally-ill patients under the FDA “Compassionate care” policy is not considered apart from the treatment of other patients. More importantly, it is not clear that the terminally-ill patient, under the “right to try” conditions, can proceed with an experimental drug treatment in the absence of an IRB review and/or approval. I submitted the “Compassionate car” policy and the “right to try” policy to my University IRB to ascertain the impact on the IRB review for the treatment of terminally-ill patients. Seemingly, this has not been an issue that has previously been presented to the IRB; so, deliberation is now underway.
For the described above, any delaying IRB review and approval process that would be detrimental to the terminal patient would be unreasonable. It is essential that the combined FDA process and the IRB process be expeditious and consistent with the welfare of the terminally-ill patient.
Although the “right to try” bill received strong political bipartisan support and widespread public support, there has also been significant opposition. The following presents some of the opposition issues.
Some health organizations raised concern that the bill “could do more harm than good to seriously ill patients.” Terminally-ill patients cannot have greater harm than their impending death.
“The Thalidomide birth defects exemplifies the problems that can result when drugs are given to humans without proper safety review and approval.” This most unfortunate incident (which led to some of my early research) occurred in the early 1960s; during the time clinical trials did not require FDA approval, nor were they subject to oversight.
“The phase I determination of the drug safety is insufficient to establish the safety in a large population; which requires months and even years to establish.” The modified phase 1 requirement for safe treatment is limited to the “Compassionate Use”. The more stringent safe use of evidence still applies to other conditions.
“The goal of clinical trials should not be a right to try, but a right to have safe, effective, affordable drugs that do not drive people to medical bankruptcy.” For the terminally-ill and their loved ones, avoiding death is a major consideration.
Comments, as presented by the above, are likely the views of individuals who have not encountered or endured a relationship with a terminally-ill situation; and thereby do not exhibit empathy or even sympathy for such conditions. I know from first-hand experience the personal impact that develops during my interaction with untreatable terminally-ill metastatic prostate cancer patients. They (and often with their physician) initiate via email an inquiry of the application of the treatment regimen to cure their terminal condition. This generally results in email communications and sometimes conference calls, which then leads to a close relationship.
The frustration has been that the drug treatment regimen is not FDA approved for prostate cancer treatment; which would take months and years for FDA approval. However, an alternative approach is the “off-label” use of an FDA approved drug for a different medical application than the initial approved use of the drug. The combination of “right to try” and the ‘off-label” policies is now being applied to the author’s treatment of current terminally-ill metastatic prostate cancer patients; thus, eliminating the complex process and extensive period of time that has been detrimental for terminally-ill patients.
The author of this presentation is Professor Leslie C. Costello. He received the M.S. and PHD degrees in 1952 and 1957 from the University of Maryland. He served as Chairman of the Department of Physiology at the Howard University School of Medicine and at the University of Maryland School of Dentistry. Dr. Costello is currently Professor of Physiology and Oncology at the University of Maryland School of Dentistry Department of Oncology and Diagnostic Sciences; and the University of Maryland Greenebaum Cancer Center.
Dr. Costello has achieved a career record of receiving more than 50 years of funded research grants which include 31 grant awards, including 23 NIH grant awards. The achievement of more than 50 years grants support is a rare achievement among a small number of investigators since the beginning of NIH in 1946 as an extramural granting agency.
He is a pioneer in prostate cancer and other cancers with about 200 publications and book chapters relating to prostate and other cancers over the past 45 years and currently; and is Co-editor on the recent book “Mitochondria and Cancer”.
He has been invited speaker at many international cancer conferences. He recently presented the talk “The role of zinc in the normal prostate; and decreased zinc in the development and progression of ZIP1-deficient prostate cancer. The basis for a zinc ionophore approach for the prevention and treatment of prostate cancer “at the 2017 International TOTT Cancer Conference.
Dr. Costello is listed in the group of the top 5% of biomedical researchers in the world.