The “Right-to-Try” experimental drugs act passed by Donald Trump...

The “Right-to-Try” experimental drugs act passed by Donald Trump in 2018 provides an opportunity of early access to experimental drugs for the treatment of life-threatening diseases and a potential boon to many young and under-capitalized biotechnology or pharmaceutical companies. The pros and cons of experimental drugs, including a number of “cutting edge” scientific, clinical, and a number of synergistic approaches such as artificial intelligence, machine learning, big data, data refineries, electronic health records, data driven clinical decisions and risk mitigation are reviewed.
Over a century ago, most medications were the “wild west” with alleged therapeutic benefits. Most such medications sold to the public offered negligible or no evidence-based therapeutic efficacy and safety to the patient at large, except the “placebo benefit”—and hope—at the best. The drugs were unregulated and sold to the public in the USA and many parts of the world. To protect the public against the sale of misbranded, mislabeled and/or adulterated foods and drugs, the US in 1906 enacted [1] the “Pure Food and Drug Act” and this resulted in the establishment of the federal agency, the Food and Drug Administration (FDA).

Historical overview

The “Right-to-Try” experimental drugs, however, originated [2–4] from the Abigail Alliance for Better Access to Developmental Drugs versus von Eschenbach. Due to Abigail’s high expression of EGFR, her oncologist recommended Abigail for her terminal head and neck cancer to try an investigational EGFR-targeted drug, C222 (Erbitux), which was then undergoing clinical trial for the treatment of colorectal cancer. Due to her ineligibility to participate in the clinical trials and denial by the FDA, Abigail’s father, Frank Burroughs sued the FDA in 2003 for access to the experimental drug, Erbitux, on the pretext that an investigational drug by terminally ill patients after phase I approval was a constitutional right. Abigail’s tragic story was one of the primary precursors and a “catalyst” that inspired patients and non-patients, including advocacy groups for access to unapproved therapies by the FDA.

In May 2018, President Donald Trump signed the “Right-to-Try” Act [5]. The legislation overcame many of the regulatory barriers, limited the risks to the sponsor while implementation of the act inherently burdened the sponsor. The “Right-to-Try” legislation is in essence a derivative of the Expanded Access Programs (EAPs). Advocates such as patients, families, friends and advocacy groups of the “Right-to-Try” legislation argue that the legislation is in line within the pre-existing framework of EAPs and that the legislation: (i) provides a “streamlined” avenue for making eligible drugs available to eligible patients with no other options; (ii) it increases patient’s engagement; (iii) it is a patient’s journey of self-actualization; (iv) it empowers the patient about his or her own health, well-being and quality of life; (v) it provides optimism and access to novel interventions with potential therapeutic benefits that may prolong life and improve quality of life; and (vi) the patient can be treated in the USA with valuable family time, more comfort and fewer risks than being treated overseas. The critics, on the other hand, argue: (i) there is an inherent safety risk that may potentially cause more harm to the patient or even death than the benefit because the experimental drug did not undergo rigorous testing; (ii) there is a lack of oversight by the FDA, except posting of the consolidated annual summary report; (iii) the patient in most cases has limited understanding of the informed consent due to complexity and confusion of the medical terminology used in the consent form; (iv) there are therapeutic misconceptions combined with high expectations and optimism by the patient; (v) there is potentially a considerable financial burden by the patient or the patient’s family because payors currently do not provide coverage and deny hospice care; (vi) there is a potential loss of trust in the regulatory agency, the sponsor and the health care provider; and (vii) there is a liability “immunity” for the health-care provider, including the drug sponsor for potential negative outcomes of the treatment unless the medical provider and the sponsor were engaged in “gross negligence, reckless or “wilful misconduct.”

Some of the major inherent limitations and often overlooked about the “Right-to-Try” experimental drugs are: (i) patient’s vulnerability due to lack of oversight by the FDA; (ii) there is a lack of clinical study protocol, including the lack of sufficient statistical power to detect the intended effect(s); (iii) the information is collected in a “piece-meal”; and (iv) a lack of systematic reporting about efficacy and the safety of the experimental drug that may potentially result in limited information for the health and safety of the public. Some of these issues may be addressed and resolved by utilizing EHR systems. EHR systems are maintained by health care providers and health care organizations for delivering patient care. EHR systems can thus easily lend themselves for integrating real-time electronic health care information about the patient across multiple health care providers.

One of the most important considerations and occasionally overlooked is comorbidity; it is quite common among cancer patients and it can potentially affect the treatment outcome, worsen the adverse effects due to polypharmacy and may even shorten the life. The prognosis of patients with comorbidity is often poor survival combined with poor quality of life and higher financial costs. The use of experimental drugs in patients with morbidity may thus be risky or limited unless the experimental drug has gone through further rigorous testing and/or the experimental drug is paired synergistically with an FDA-approved drug and appropriate tools are employed for monitoring efficacy and safety of the therapy. Treatment of metastatic cancer patients with comorbidity using experimental drugs would be even more challenging and riskier with many implications that may warrant further considerations that are in the best interest of the patient’s health, well-being and life, including additional financial burden.