This week’s readings explore Pharma’s strategies for, and the moral issues involved in, the recruitment of clinical trial participants (CTP’s), especially from vulnerable populations.
A Synopsis of the Readings
Jill Fisher’s “‘Ready-to-Recruit’ or ‘Ready-to-Consent’ Populations?”
Fisher argues that Pharma, and in particular Contract Research Organizations (CRO’s) take advantage of “ready-to-consent” populations, such as the uninsured, poor, or traditionally disenfranchised, who lack “better alternatives than participation in clinical trials” (876). To illustrate, she describes three case studies: one where a son decides his mother, who has Alzheimer’s, should participate in a possibly dangerous clinical trial (CT) to get an expensive MRI (387); another where an uninsured woman uses a CT to get expensive medication to control her “overactive bladder” (388-9); and a third where an impoverished Hispanic woman participates in a healthy human study for monetary compensation (388-89). Such cases demonstrate how desperate CTP’s are motivated by desires to have access to medical or financial resources otherwise unavailable to them.
Fisher further asserts that informed consent—currently considered by the FDA as the standard for legitimatizing clinical trial participation— is insufficient to safeguard the “rights and welfare of human [research] subjects” (878). For one, the “screening and consent” process to choose CTP’s begins well before someone visits a research center, and Fisher thinks “most prospective humans have already decided to take part in clinical studies before receiving the informed consent forms” or hearing safety risks for a trial (879). For instance, the son in the first case study is repeatedly told by a doctor that his expectation of therapeutic benefit for his mother is unrealistic, but he still reasons the trial will help his mother get access to a diagnostic MRI. This suggests that “all the informed consent visit achieved was to give [the son] new reasons for justifying [his mother’s] participation” (886). Similarly, participants in the two other case studies could not recall safety risks mentioned in their “informed consent forms.” This may be evocative of how CTP’s are influenced to give consent by mass-media advertising, which will often emphasize potential benefits of CT— such as possible new treatments, and “free” consultations and medication for participants— while glossing over dangers of clinical trial participation— such as possible safety risks or chances a “treatment” may be ineffective.
Thus, Fisher thinks “informed consent” is insufficient to protect CTP’s from “research abuses” (389), and she emphasizes a need to consider the “structural conditions” that make CT’s attractive to “ready-to-consent,” vulnerable populations (891).
Steven Epstein’s “The Rise of ‘Recruitmentology’”
Epstein discusses the science of “recruitmentolgy” that has resulted from increased pressure on researchers to have a diverse mix of CTP’s from a range of ethnicities, genders and ages, as a result of policies implemented by the US Congress, FDA & NIH (National Institute of Health; 806). This intended diversity of CTP’s is meant to satisfy an “inclusion-and-difference paradigm” for research, whereby populations that have traditionally been under-represented in medical research— racial minorities, women and children for instance— are included as research subjects, and differences in terms of treatment efficacy or disease effects between demographic groups are also explored (802).
However, recruitment of demographically diverse subjects can be extremely difficult, expensive and time-consuming. The supply of available research bodies rarely exceeds demand, and members of minority groups are suspicious of CT’s, oftentimes because of “historical and political issues” surrounding research experimentation in their communities (815). For instance, African-American populations have frequently been treated as human “guinea pigs” (814). A prime (but not the only) example of this is the Tuskegee Syphillis study, where uneducated, black participants in a study on Syphillis were not given information about treatments for Syphilis which had been developed during the course of the study. Similar historical injustices involving abusive and exploitative research practices are embedded in the collective memory of many other minority groups, particularly Hispanics and Native Americans, making recruitment from these populations difficult.
Today, injustices from CT research risk repetition on a global scale, with trials increasingly being outsourced to developing countries with less stringent legal and ethical barriers for conducting research (819). In such countries, Pharma has allegedly used illiteracy to side-step the process of getting informed consent, denied post-trial care to CTP’s, and given research subjects in control groups medications well below American “standard of care” treatments (819-20).
In response to this pressure for diverse clinical trial populations, Epstein discusses the emergence of a science he terms “recruitmentology,” which refers to the empirical study of evaluating “various social, cultural, psychological, technological, and economic means of convincing people (especially members of ‘hard-to-recruit populations’) that [Pharma players] want to become, and remain, human subjects” (801). In practice, recruitmentology involves researchers using publications and conferences to share recruiting experiences, exploring communal attitudes to research, studying the social networks that must be navigated to make recruitment successful, and attempting more formal analyses to quantify, synthesize & compare different recruitment strategies (810). Thus, recruitmentology emphasizes both “hard” and “soft” sciences.
Epstein both praises and criticizes aspects of recruitmentology. He praises literature in the sepciality that seeks to transform the traditional “power imbalance” between researchers and communities of CTP’s, by having the two groups engage closely with each other in the research process, with community groups helping determine research priorities and procedures as equal “partners” in research. However, he finds the often ineffective attempts at a formalization of recruitmentology problematic, as these efforts can reinforce “essentialist definitions of races as discrete groupings that differ from one another in presumptively biological ways” (802), while also exacerbating a view of minority populations as existing to satisfy a researcher’s “pre-given interests” (813).
Kaushik Sunder Rajan’s “The Experimental Machinery of Global Clinical Trials”
As clinical trials become increasingly globalized, Rajan describes the concentrated efforts by several “Indian actors” to develop attractive and robust institutional, technical and ethical infrastructure to accommodate the anticipated movement of global trials to India (58). These “actors” include a growing industry of profit-oriented CRO’s, pharmaceutical companies looking to invest more in Research and Development, regulatory bodies such as the FDA-like Drug Controller General of India (DCGI), certain educational institutions that train CT researchers, and (to a lesser extent) the physicians conducting CT.
The results of these efforts? In addition to more CRO’s, there is an increased presence in India of data management organizations which can process CT data. There are educational institutions that offer diploma courses to train young professionals in conducting clinical research. There are also efforts, often driven by CRO’s, to standardize and make stringent regulatory frameworks for clinical trials in accordance with international standards using ICH protocols (67). For instance, the Indian government has produced guidelines for “Good Clinical Practice” (GCP) when doing CT research, violation of which is considered a criminal offense (67). Hence, far from CRO’s being able to cut “ethical corners,” Rajan emphasizes efforts to implement international standards for CT research in India, particularly focussed on ensuring informed consent is given by CTP’s. Partially as a result of these infrastructure changes, and also because of low costs and the presence of large treatment-naïve populations, India now ranks amongst the most attractive destinations for clinical trials and has recently seen a 20-25% increase in contract research per year (58).
However, the outsourcing of clinical trials to India raises unique worries. Current legal frameworks and pharmaceutical policies offer “no guarantee” that experimental drugs, once approved, will be marketed or made affordable to the Indian populations used to test them (70). Further, aside from occasional “compassionate-use programs,” Pharma players rarely guarantee CTP’s continued access to medication after a trial, even if a drug proves effective and participants come to depend on them (71). Additionally, Rajan is critical of how the “ethical figuration” of CTP’s is codified merely by informed consent procedures, which ignore the “structural violence” that induce many CTP’s to take part in research, such as unemployment, poverty or an inability to pay for medication (73-5). In the current context, Rajan thinks there is a “structural impossibility” in Indian of experimental subjects becoming “political [subjects],” meaning the conditions needed for CTP’s to mobilize politically are contingent on several factors outside their control, making these participants vulnerable to abuse and exploitation.
Some Questions to Contemplate
1) Pharma might be seen as giving already desperate people access to medical or financial resources they otherwise would not have. Hence, do clinical trials exacerbate inequalities of healthcare access, or might they actually alleviate those inequalities?
2) Fisher claims she does not advocate for a prohibition of clinical trial participation from vulnerable populations (890). If not prohibition, what are some constructive guidelines to protect vulnerable populations from research abuse in CT?
3) Epstein and Fisher make two seemingly contradictory claims. Some minority populations Fisher identifies as “ready-to-recruit” are ones Epstein identifies as “hard-to-recruit.” Who is right? Might the increased scrutiny many minority CTP’s are likely give to informed consent forms, due to historical suspicions, alleviate some of Fisher’s worries?
4) CTP’s are often referred to as “volunteers” by Pharma ( Rajan 70). Clinical trials are rarely advertised as “experiments.” The word “free” is used by advertisers to characterize the medication and consultations received by CTP’s (Fisher 882), though participants sacrifice their time, privacy and bodies to researchers. How does the language used by Pharma shape conceptions of CT participation?