Weighing risks for ‘trial subjects’ against societal benefits

As pointed out earlier, pharmaceutical development entails an element of risk for the volunteers and patients enrolled in clinical trials, and the potential benefit for patients should be seen in light of this risk. When viewing clinical trials officers’ emphasis on helping patients, they are aware of the risk factors, but assume that these risks are worth taking when a potential new product is in sight. In fact, one could argue that the ordinary ethics underlying the entire process of pharmaceutical development is imbued with such risk judgments: An unknown substance is tested, and this testing involves an element of risk and on a few occasions in the history of the industry (See e.g. Horvath and Milton 2009), has caused severe injury or even death among the people being tested. However, the rationale for testing is its long-term benefit: the testing is conducted on a limited number of people with the purpose of potentially benefitting a larger group of patients in the future and ultimately, society. The risk

involved in testing is deemed justifiable because of the prospects of a greater good in the future (here, understood as the development of a new treatment for patients). The criteria against which ‘the good’

is evaluated is the potential benefit for a large group of people, and thus the ordinary ethics of clinical trials lies in this criteria (cf. Lambek 2010b).

99 “People come first at Ferring. Because: Patients using our products and physicians prescribing them have a right to expect:

• that we will only make available those products in which we have full confidence.

• that we will offer the best possible products at the most reasonable cost.

• that Ferring's employees will always display courtesy and respect, and act professionally.

Ferring seeks the loyalty of these patients and physicians, and we are prepared to earn this loyalty anew every day.’

169 This kind of logic (risk now, potential benefits later) is not limited to pharmaceutical companies, of course. The agencies responsible for approval of new drugs likewise demand that these substances have been tested on humans according to international guidelines for doing so, before they can be approved and sold. Returning to the Declaration of Helsinki introduced earlier, the Declaration begins by stating a number of general principles, also set forth in other declarations:

‘The Declaration of Geneva of the WMA [World Medical Association] binds the physician with the words, ‘The health of my patient will be my first consideration,’ and the

International Code of Medical Ethics declares that, ‘A physician shall act in the patient’s best interest when providing medical care’.’¹⁰⁰

What is noteworthy is how the language changes when moving into the general principles of the declaration, where the term to describe trial participants changes from ‘patients’ to ‘subjects’.

In the general principles of the declaration, it thus further states that ‘Medical progress is based on research that ultimately must include studies involving human subjects’¹⁰¹ but that ‘While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects’¹⁰². Thus, in order to progress, new treatments must be tested on human subjects, but still keeping in mind that the health of the patient is the primary consideration, cf. the introductory quote above. As mentioned earlier, in the first phase of

pharmaceutical testing, so-called ‘healthy volunteers’ are enrolled in the trial, and patients are not enrolled until the subsequent phases two and three. The term ‘trial subject’ thus presumably intends to cover both patients and non-patients. However, in clinical trial protocols and internal standard

operating procedures (SOPs) and internal communication within clinical trial teams in Ferring, the term

‘subject’ is also used in phases two and three trials to refer to the patients who are enrolled.

Returning to the Declaration of Helsinki, under the headline ‘Risks, Burdens and Benefits’, the

Declaration further states its position on the risk involved in clinical trials on humans, stressing that the potential benefits of conducting a trial must always outweigh the risks. Hence:

100 Declaration of Helsinki, point 3. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/

101 Declaration of Helsinki, point 5

102 Declaration of Helsinki, point 8.

170

‘16. In medical practice and in medical research, most interventions involve risks and burdens.

Medical research involving human subjects may only be conducted if the importance of the objective outweighs the risks and burdens to the research subjects.

17. All medical research involving human subjects must be preceded by careful

assessment of predictable risks and burdens to the individuals and groups involved in the research in comparison with foreseeable benefits to them and to other individuals or groups affected by the condition under investigation.

18. (…) When the risks are found to outweigh the potential benefits or when there is conclusive proof of definitive outcomes, physicians must assess whether to continue, modify or immediately stop the study.’¹⁰³

What we learn from the declaration, then, is that the best interest of the patient always comes first. We further learn that testing on ‘human subjects’ is a precondition for medical progress, but that such testing involves risks and burdens. Hereby, a slightly paradoxical element enters the declaration, as the care for the individual subject’s well-being competes against the goal of medical progress. Although it is clearly stated that the interest in furthering research must not take priority over the well-being of an individual subject, it is also stated that clinical trials will involve certain risks and burdens imposed on the ‘subject’. And the question arises how one can maintain the best interest of the individual subject while also subjecting the individual to risks. This, it becomes clear from the declaration’s points 16-18 stated above, is a matter of weighing the potential benefits of such a trial with the potential risks to the subject. However, while the potential benefits may help a larger group of patients – also outside of the study if it is completed and shows successful – the potential risks are imposed only on the individual test subjects who participate in the trials, some of whom may not be patients at all.

Similarly, within the aforementioned GCP guidelines, according to which clinical trials are designed, weighing potential risks and potential benefits is also a central concern. These guidelines are based on 13 principles, and contain a similar paradox of ensuring trial subject safety while still recognizing the existence of potential risks for this very subject. Observe, for example, the first three principles of the ICH GCP:

103 Declaration of Helsinki, point 16-18.

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‘1. Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).

2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.

3. The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.’¹⁰⁴

As stated above, risks and inconveniences for individual ‘trial subjects’ should be weighed against the anticipated benefit for this subject who participates in the trial as well as the benefit for society.

However, in Principle 3, it is established that the interests of society should not take priority over the interests of the individual subject. Thus, any potential risk should only be taken if the potential benefit for the subject and for society is deemed larger than this risk. This assessment raises the question of how such incommensurable benefits and risks are weighed against each other in practice and what logics are guiding – and constituted by - this exercise.

As Lambek (2010a) reminds us, the ethical is not confined to specific moments, domains or specific types of questions. Ethics is a part of our daily practices, and is embedded in the logics with which we evaluate and judge what is right or wrong. ‘Ethics’, he argues, is to strive towards a particular

conception of the good, and ordinary ethical practice entails having to make judgments between different, sometimes incommensurable goods. Lambek thus refuses to demarcate the ethical as and define it as something, arguing instead that the ethical lies in this striving and in the discriminations that we make between competing choices, between the many competing roads we could take.¹⁰⁵

In the following, I will turn to three ethnographic examples where such ordinary ethical weighing of risks for a subject and benefits for a (future) patient, as recommended by the Declaration of Helsinki and ICH GCP, is conducted in practice. I have chosen these examples in order to show how clinical trials officers, as described earlier in this chapter, deem the Ferring Philosophy redundant because of their existing ‘mission’ to develop products that will help patients. However, as I will point out, their notion of patients is rather narrow. It is focused on those patients who can be helped in the future rather than

104 Good Clinical Practice (GCP) E6(R2), page 15 https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-6-r2-guideline-good-clinical-practice-step-5_en.pdf

105 Based on conversation with Michael Lambek in Toronto, October 2019.

172 on those ‘subjects’ who are part of the present-day trial. The first two examples illustrate a prevalent interpretation held by clinical trials officers of Ferring’s code of ethics: that the ‘people’ who come first are the patients as the end-users of the products. At the same time, in practice, the people who participate in the trials are defined as ‘subjects’. These subjects, or the situation they are in, compete with a number of other considerations when clinical trials officers make ordinary ethical judgments.

The third example explores the boundaries for this interpretation and illustrates a tipping point when the ‘subject’ participating in the trial becomes a ‘patient’ and takes priority over the future patient for whom the products are being developed.

While the first ethnographic examples have been selected among many, illustrating themes that have been prevalent throughout the fieldwork, the third example has been selected because of the richness of the account and the specific situation it portrays. In particular, it highlights the limits of the temporal displacement whereby the welfare of an existing subject is subordinate to the future patient.