Ius Gentium

University of Baltimore School of Law's Center for International and Comparative Law Fellows discuss international and comparative legal issues

International Clinical Trials: Shaky Grounds for Bioethics

Leave a comment

Jasen Lau

Isai in the Moldavian region of Romania, Megrine in northern Tunisia, Tartu in Estonia, and Shenyang in Northern China all have something in common. Unfortunately, they are not the world’s best vacation spots. No, large pharmaceutical companies have targeted these locations as places to run clinical trials.[1] These towns are among many similar towns – poor, distant, and isolated from major cities – that are often favored by many pharmaceutical companies. This recent globalization of clinical trials has raised many questions about both the ethics and efficacy. As international clinical trials grow in popularity, serious consideration needs to be given to the bioethics of conducting such trials in developing countries.

Clinical trials are the backbone of pharmaceutical development. The Food and Drug Administration (FDA) requires them before a drug can be marketed to the public.[2] Clinical trials are often broken into four segments – Phase I, II, III, and IV – and are used to assess the safety and efficacy of the developing drug.[3] Phase I begins with a smaller sample – usually around 20 to 30 people – and is the most dangerous part of the trials.[4] Phase I is where the level of safety and efficacy of the medication is mostly unknown. As the trials progress to Phases II and III, so, too, do the number of participants. Phase IV is post-market observation.[5] This phase monitors the drug after it has been released and is meant to document what effects arise from large-scale use. Clinical trials are meant to uncover the dangers and risks of medication, but this procedure can often take a lot of time and money.

JL Blog1_Photo1

Most clinical trials can take around a decade.[6] During such time, costs can be around $2.6 billion – not including post-market procedures.[7] These costs come from advertising, subject compensation, and general research procedures, like conducting international clinical trials. With such high costs, many pharmaceutical companies seek to lower costs. International clinical trials have been very popular since 2008.[8] Currently, roughly 60% of the clinical trials being conducted are recruiting research subjects outside of the U.S.[9] By conducting trials overseas, pharmaceutical companies are saving vast amounts of money. For example, in India, a case report from a “first-rate” research center costs $2,000, which is less than one tenth the cost of recreating that same report in a “second-tier” research center in the U.S.[10] This is where the research subjects from developing countries come into play.

In nations where income is low[11], the chance of receiving state of the art medicine is a welcomed opportunity. However, in these remote locations where the US holds no jurisdiction, what assurances do these subjects have that they will be treated fairly? The Nuremberg Code requires basic ideas such as voluntary consent, maximizing benefits while minimizing costs, and taking patient care as first priority.[12] In addition, the Declaration of Helsinki expands upon this and includes the idea of protecting vulnerable populations (the elderly, incarcerated, pregnant, and children), a duty to protect the integrity of the patient, ensuring that those who are harmed are compensated.[13] These codes are meant not just for the U.S. but the global practice of medicine. It is important to note, however, that these ethical guidelines are precatory – not mandatory. Further, prior to the start of the trial, research groups must submit their proposal or application to an Institutional Review Board (IRB). These IRBs are comprised of both medical and non-medical staff that determine the safety of the trial and ensure the welfare of the test subjects.[14] While these protections are in place, the question becomes to what extent and how thoroughly do these guidelines and procedures protect the subject?

WebBanner

Informed consent is one of the many things required when conducting research. Without going too deeply into the nuances, what true choice do these subjects from developing countries have? Even in a developed country, such as the U.S., many scholars have speculated the true need for informed consent in the practice of medicine.[15] In the end, in part due to the extreme disparity in medical knowledge expertise between subject and researcher or patient and doctor, the subject is more or less consenting to the trustworthiness of the doctor – not the actual procedure. Likewise, the subjects of these nations may not truly be consenting to the research procedure. Rather, their need for medical care at no cost to them greatly incentivizes assent. If that is the case, what point is there, then, in informed consent for these kinds of subjects?

IRBs play a key role in approving clinical trials. However, they are American citizens. Their job is to determine if the trials are ethical and take patient welfare into consideration, but they are not present to routinely monitor the clinical trials.[16] Even the FDA, those who ultimately approve a drug based on these trial results, do not inspect all – nor even a significant number of – these international clinical trials. In fact, the FDA inspects only around 0.7% of such trials.[17] If an IRB is not physically present to protect patient welfare, and the FDA seldom inspects these trials, who is actually protecting these test subjects?

JL_Blog1_Photo2

 

With the benefits of a relatively large population, all of whom are nearly always willing to partake in studies, and being outside the jurisdiction of the FDA, pharmaceutical companies are greatly incentivized to conduct their research outside of the U.S. There is concern that this will eventually lead to more harm than benefit. There is no assurance that researchers will abide by ethical guidelines, and even if the researchers practiced according to those guidelines, harm can still come to the subjects. When a test subject is harmed, where are they to turn for treatment? Or does this globalization turn a cold shoulder to international research subjects? Further, if the medication is mostly tested on international citizens, whose diets, lifestyle choices, and environmental factors greatly differ from American citizens, how safe is the medication for the average American?

 

The unfortunate conclusion to these rhetorical questions is that clinical trials are growing ever more appealing. While there is not yet currently any solid argument for harm, the obvious threat looms over subjects from developing countries. Such subjects, in need of modern western medication, may not be able to give informed consent to research. Yet, without these treatments, some of these subjects will be no better off than before. Globalization of clinical trials leads to a plethora of bioethics issues, and as it often is with bioethics, there is rarely a concrete answer now nor will there be one in the near future. Adding on the increased complexity of international jurisdiction, the question is whether these American pharmaceutical companies should be made more responsible, and if so, who should – or can – enforce that kind of duty or even impose it? The best thing that can be done at the moment is consistent, thorough analysis of all clinical trials. At the very least, the FDA should increase investigation of these international trials. The future merely holds a balance of powers and desires: cost-saving options for pharmaceutical companies and the bioethics thereof versus the length of reach of FDA’s regulatory authority.

Jasen Lau is a third year law student at the University of Baltimore School of Law. He graduated from the University of Maryland in 2013 with a Bachelor of Arts in English. Jasen took it upon himself to become a certified pharmacy technician and studied several continuing education credits that focus on Medicare Fraud and Abuse prevention, HIPAA privacy and security laws, and ethics in the pharmacy workplace. Jasen has long been in the health care field either working directly with patients or as an assistant to providers. During that time, his obsession with working in health care has grown into policy analysis and counseling. Along with being a CICL fellow, he is also a law clerk for Johns Hopkins Hospital.

[1] Donald Barlett & James Steele, Deadly Medicine, Vanity Fair, Jan. 2011, http://www.vanityfair.com/news/2011/01/deadly-medicine-201101.

[2] Step 3: Clinical Research, U.S. Food and Drug Admin., Nov. 23, 2015, http://www.fda.gov/ForPatients/Approvals/Drugs/ucm405622.htm.

[3] Id.

[4] Id.

[5] Id.

[6] Cost to Develop and Win Marketing Approval for a New Drug is $2.6 Billion, Tufts Ctr. for the Study of Drug Dev., Nov. 18, 2014, http://csdd.tufts.edu/news/complete_story/pr_tufts_csdd_2014_cost_study.

[7] Id.

[8] Daniel Levinson, Challenges to FDA’s Ability to Monitor and Inspect Foreign Clinical Trials, Dept. of Health & Human Serv., June 2010, http://oig.hhs.gov/oei/reports/oei-01-08-00510.pdf.

[9] Trends, Charts, and Maps, ClinicalTrials.gov, February 2016, https://clinicaltrials.gov/ct2/resources/trends (54% of the studies are recruiting exclusively outside the U.S. while an additional 6% is recruiting both in and out of the U.S.).

[10] Seth Glickman et al., Ethical and Scientific Implications of the Globalization of Clinical Research, 360 New Eng. J. Med. 816 (2009).

[11] Romania Average Salaries & Expenditures, World Salaries, (Feb. 26, 2016), http://www.worldsalaries.org/romania.shtml (Prices have been converted to U.S. currency for ease of understanding. A dentists average salary is less that $500 a month, engineers make about $700 a month, and physical therapists makes just over $400); see also China Average Salaries & Expenditures, World Salaries, (Feb. 26, 2016), http://www.worldsalaries.org/china.shtml; Occupational Employment and Wages, May 2014, Bureau of Labor Statistics, Mar. 25, 2015, http://www.bls.gov/oes/current/oes291021.htm; see also Occupational Employment and Wages, May 2014, Bureau of Labor Statistics, Mar. 25, 2015, http://www.bls.gov/oes/current/oes291021.htm (The average salary of dentists and physical therapists is about $14,000 monthly and $6,800 monthly, respectively).

[12] The Nuremberg Code, U.S. Dept. Health & Human Serv., Nov. 7, 2005, http://www.hhs.gov/ohrp/archive/nurcode.html.

[13] WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, World Med. Ass’n, (Feb. 26, 2016), http://www.wma.net/en/30publications/10policies/b3/.

[14] Clinical Trials, MedlinePlus, January 28, 2016, https://www.nlm.nih.gov/medlineplus/clinicaltrials.html.

[15] Peter Schuck, Rethinking Informed Consent, 103 Yale L.J. 899, 1994.

[16] Glickman, supra.

[17] Levinson, supra at 15.

 

Advertisements

Author: Ius Gentium

Ius Gentium is a legal forum for the University of Baltimore School of Law's Center for International and Comparative Law Fellows to write on and discuss international and comparative legal issues.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s