Unraveling the Ethics Behind Experimental Drugs

Aman Mistry, Grade 11

As the death toll due to COVID-19 increases, the ethical jumble surrounding experimental therapies becomes prevalent. Emergency situations such as the COVID-19 pandemic reassert the ongoing controversy surrounding the use of experimental drugs (2). Experimental drugs are preliminarily approved for clinical trials and can be alternatives to treat patients in times of crisis such as the COVID-19 pandemic or when suffering from a terminal illness (1, 2). Experimental drugs should be used out of beneficence and fairness despite the unanticipated side effects and substantial costs; however, the standard of care must have been attempted and the drugs should have Phase I drug approval prior to implementation.

Various negative aspects of experimental drugs result in the controversiality in their use in spite of increased COVID-19 deaths. Hydroxychloroquine, an experimental drug for COVID-19,  prevents viral entry into cells and has its intended effect in vitro. Yet there is no conclusive evidence to ascertain results in humans (3, 4). If drugs are not approved before use, the results can be detrimental as seen when highly active disease-modifying therapies led to unintended side effects in multiple sclerosis (5, 6). As a result, some challenge that even in times of emergency or terminal illness it is unethical to treat someone with drugs that have not been vetted as some side effects may not be anticipated. This claim is substantiated since the “compassionate use,” of experimental therapies can lead to uninformed and perhaps fatal decisions due to the desperation of patients with incurable diseases and their families (5).

On the other hand, administering an experimental drug to a patient with a terminal illness or a patient with no viable alternatives in emergencies can render potential benefits as opposed to their anticipated death. Since some patients with terminal illnesses do not have any functional drug alternatives and since an unapproved drug could still have some level of effect, experimental therapies are an alternative treatment with the potential to improve a patient’s condition (5, 7). This point is demonstrated by both the EU and the USA as they have legislation affirming that patients near death can have access to experimental therapies if the standard of care has failed (1, 8). For instance, experimental therapies for multiple sclerosis such as hematopoietic stem cell transplants have resulted in 70% of patients having no disease activity for 5 years (6). The obscurity of safety and efficacy concerning experimental therapies in comparison to the impending death of terminally ill patients are ethically minimal. Experimental therapies also have the potential to improve the conditions of individual patients. Remdesivir, an experimental therapy for SARS-CoV-2, has shown statistically significant improvement in recovery time in phase 3, double-blind, randomized, and placebo-controlled tests. Patient hospitalization decreased from 15 to 11 days indicating the benefits of experimental therapies in times of emergency (9). This point is corroborated by the fact that the FDA drug approval process does not account for the localized effects of experimental drugs. Experimental drugs can help subgroups of a population such as the chemotherapy drug, Isoniazid, which could save a specific group of patient’s lives (10). Experimental drugs can also be of aid in emergency. In the COVID-19 pandemic, drugs are needed promptly due to the increasing number of people dying from COVID-19 (3). The FDA could take years to approve drugs such as when it took over a year to approve zidovudine for AIDS (5). In emergencies such as the AIDS outbreak, if experimental therapies are rapidly implemented on those near death, researchers can gain knowledge concerning its efficacy and potentially save the lives of the patients in testing.

Furthermore, a patient’s free choice is an imperative right that presents conflicts with experimental drug use. Since it is the patient’s life, some believe the patient should have the right to determine if they want to receive experimental drugs (11). Numerous states have acknowledged this and have established the “Right to Try” laws in which drugs that progressed past Phase 1 drug approval process are permitted to be used on patients with their consent (5, 12, Figure 1).

Image of the Drug Approval Process Infographic (Vertical Format)
Figure 1: FDA Phase 1 drug testing description.

Experimental therapies should be used with prudence; they should be rapidly tested and those that prove efficacy in Phase 1 of the FDA approval process should be allowed in times of crisis (5). Due to patient desperation, the process should be informed and transparent. In order to aid the patient’s decisions, the patient should be familiarized with drawbacks and other approved drug options; once this is complete, the drug can aid in times of emergency.

Experimental drugs can not only affect individual people but can have a societal impact. High demand for experimental therapies as seen by the Abigail Alliance and social media pressure display that approving experimental drugs is desired by society (8). Experimental drug use will expand the rights of the patients in need of the drug and give the rights to experimental drug use back to society.

Experimental drugs come at the risk of exacerbating the situation, however, in times of emergency with appropriate caution being taken they have the potential to improve the lives of patients with incurable diseases and patients in emergencies. Expanding access to these drugs can lead to uninformed decisions but can also secure the rights of citizens. However, forming an equipoise between the negative and positive aspects of experimental therapies such as permitting their use post Phase 1 drug approval can facilitate the incorporation of experimental therapies into the armamentarium against potentially fatal diseases in emergencies. Realizing the controversiality and ethical concerns behind experimental therapies is critical in forming one’s opinion on their use in times of emergency.

[1] K. Raus, An Analysis of Common Ethical Justifications for Compassionate Use Programs for Experimental Drugs. BMC Med Ethics 17, 60 (2016). doi: 10.1186/s12910-016-0145-x
[2] S. Charache, EXPERIMENTAL THERAPY. Hematology/Oncology Clinics of North America 10, 1373-1382 (1996). doi: 10.1016/S0889-8588(05)70408-1.
[3] D. Bogdanos, et al., When There is a Pandemic There is No Time to Waste: Should We Have Hydroxychloroquine in our Armoury Against COVID-19 Infected Patients?. Mediterranean Journal of Rheumatology 31, 94-97 (2020). doi:10.31138/mjr.31.1.94.
[4] P. Vijayvargiya, et al., Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof). Mayo Clinic Proceedings (2020). doi:10.1016/j.mayocp.2020.04.027.
[5] M. Delaney, The Case for Patient Access to Experimental Therapy. The Journal of Infectious Diseases 159, 416-419 (1989). doi: 10.1093/infdis/159.3.416.
[6] A. Lutterotti, Challenges and Needs in Experimental Therapies for Multiple Sclerosis. Current Opinion in Neurology 31, 263-267 (2018). doi:10.1097/WCO.0000000000000560.
[7] R. Burrows, et al., Ethics Roundtable: Using New, Expensive Drugs. Critical Care  6, 473-8 (2002). doi:10.1186/cc1533.
[8] P. Zettler, Compassionate Use of Experimental Therapies: Who Should Decide?. EMBO Molecular Medicine 7, 1248-50 (2015). doi: 10.15252/emmm.201505262.
[9] Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 – Preliminary Report [published online ahead of print, 2020 May 22]. N Engl J Med. 2020;NEJMoa2007764. doi:10.1056/NEJMoa2007764
[10] A. Malani, et al., Improving the FDA Approval Process. U of Chicago Law & Economics, (2011). doi: 10.2139/ssrn.1945424.
[11] Ebunoluwa, O. Oduwole, K. Fayemi. Ethics of Trial Drug Use: To Give or Not to Give?. BEOnline: Journal of the West African Bioethics Training Program 3, 22-40 (2016). doi:10.20541/beonline.2016.0007.
[12] A. Caplan, et al., Should Patients in Need be Given Access to Experimental Drugs? Expert Opinion on Pharmacotherapy 16, 1275-1279 (2015). doi: 10.1517/14656566.2015.1046837.

Images retrieved from:
[1] https://www.fda.gov/drugs/drug-information-consumers/fda-drug-approval-process-infographic-vertical 

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