Patients, protocol and potential profits

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.

173

‘Our purpose is to change and improve people’s lives. Our purpose is to allow families to be built all over the world, no matter what creed or composition they may be. That is a very important purpose. It is a purpose that is unique to the life science industry. It’s what makes us unique. We are not just any business. We deal in people’s lives, we deal in life and death, and doing things the right way is exceptionally rewarding. Because we do change people’s lives. We actually create health, enable families – nothing can be more purposeful than that. Not done right, we could also cause harm and damage. And we could actually take lives or at least contribute to lives not being sustained. (…) this is what drives me every day when I go to work. The opportunity to make a huge difference. And I know that’s true for, I would say, all of you. (…) we do this, at the end of the day, because we feel that we make a difference in peoples’ lives. In patients’ lives. In families’ lives. And it really helps to understand the end-user. Of course, whatever you are in, fast moving consumables, whatever business or trade, you need to know what the customer wants. But what the customer wants here is much more profound and existential than someone who is buying a new car or a new iPhone or something like that. And understanding that requires a

different depth of engagement and commitment. That’s coming back to purpose (… ) So now, how are we going to fulfil this? Because you need more than purpose. And we will talk about a few things today. And one of them is our mission and how we actually get there (…)’.

A statement of Ferring’s mission is projected on the screens to all of us who are attending the meeting online. The last of the four paragraphs in the mission statement, which is now visible on the screen, states that:

‘We are, and will continue to be, part of a transparent and aligned company. We strive to best address the needs of patients, stakeholders and costumers by collaborating across functions, experimenting and sharing our practices, and continuously learning. We are always guided by the Ferring Philosophy’.

After going through the first three paragraphs of the mission statement, the manager ends his description of how the purpose of developing new treatments to patients is going to be fulfilled in Ferring by turning to this last paragraph cited above and says:

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‘At the end of it all, we have people [the last of the four paragraphs]. So, the Ferring Philosophy defines how we are going to behave. It’s like the golden rule in many many words, and we all know it. This is how we treat each other; this is how we excel together.

This is how we treat others.’¹⁰⁶

This example has many facets that I would like to emphasize. First, this senior managers’ focus on the purpose of creating products that can help the ‘end-user’ in the future relates to the aforementioned sense of purpose among clinical trials officers of contributing positively to patients (in the future).

Second, it is noteworthy how he at the same time hints towards the risk it entails for those individuals involved in the trials by saying that if not done right, ‘we’ (i.e. Ferring) could also ‘cause harm and damage’ and even ‘take lives or at least contribute to lives not being sustained’.

Third, the manager ties the purpose of developing new treatments for ‘end-users’ to the Ferring Philosophy. Similarly to the quote, where the manager emphasizes the importance of knowing one’s customers and addressing their needs, in the mission statement that he paraphrases and which is displayed behind him, the Ferring Philosophy is also tied to the importance of addressing the needs of the patients as end-users as well as to the needs of other stakeholders and customers.¹⁰⁷

And thus, the purpose of developing treatments for the end-users who need them is tied to the messages in the Ferring Philosophy which likewise focus on those end-users. And this link between the Ferring Philosophy and the end-users, I would argue, reiterates the understanding that the ‘people’

who come first are in fact limited to these end-users; leaving the ‘subjects’ out of the group of ‘people’

who should be put first.

Thus, among clinical trials officers, as I have also outlined earlier, there is a strong sense of purpose and a strong sense of contributing positively to patients; and this is a purpose which, in my experience, they rarely lose sight of. However, this laudable goal refers to the end-users of products and not to ‘trial subjects’; and within clinical trials, considerations of trial subjects’ interests compete with a number of other considerations.

As mentioned earlier, even when following the GCP guidelines when designing and conducting a clinical trial, there are still innumerable choices to be made, as each compound and what is being tested is

106 Based on video transcript and field notes from global staff meeting, Winter 2018.

107 The costumer is not always the same as the end-user, as many products are purchased by HCPs in hospitals and clinics.

175 different. Moreover, considerations about trial design involve much more than the scientific

considerations about how to best test a given compound, and they take into account the given time span, available internal staff resources as well as the budget. The elements to be weighed against each other within a commercial clinical trial context are thus complex and many.

The context of the following ethnographic example is a phase 2 trial where the ‘trial subjects’ are patients who suffer from the condition that the drug on trial intends to treat. The purpose of this example is to illustrate the difference between ‘the patient’ as an abstraction, an image of the purpose and future outcome of the trial to which thorough and continuous attention is given in the company, as exemplified in the previous ethnographic description from the global staff meeting, and the ‘trial subject’ who must compete for attention with numerous other considerations of trial testing with its risks, routines and budgets. We will see how clinical trial officers make ordinary ethical judgments among these multiple considerations.

I am sitting together with Ellie, a clinical trial officer from one of the studies that I have been following. Last time we spoke, Ellie introduced me to the trial and the condition they were aiming to treat, and she gave me a copy of a document containing the main considerations around the design of the study. We had agreed to meet again after I had read the document in order to review the trial presentations for the investigators (doctors and nurses) involved.

Meeting in the canteen, Ellie has brought her laptop, and she asks me to look at her screen with her. She notices that I have written a lot of notes in the margins of the document she sent me and asks me to pose my questions before we begin with the presentation. I start out by asking her about the trial design, how they selected the clinics and hospitals that should participate in the trial and how they got patients to participa te, as I did not completely understand this from reading the document that she had

supplied.

Ellie explains that in the beginning, the clinical trial team wanted to have 50 sites (i.e.

hospitals and clinics) but that they ended up with close to 60 so that they could recruit a sufficient number of patients to participate in the study.

Finding the right number of sites is a balancing act, she explains, because for every site that is added to a study, the risk of variations in how the study is conducted increases.

Although the protocol is the same for all sites, she explains, for every site, there is a risk

176 that the doctors and nurses have understood it differently or that their practices are different from the other sites; therefore, a balance must be maintained. For example, having 250 sites, she explains, would make patient recruitment much faster but this would also increase the risk of errors. The errors that she refers to, she explains, can affect the data quality, but they could also have consequences for the efficiency of the test drug on trial subjects. This angle, however, does not take up much of the story when she explains these different considerations, and Ellie does not mention any potential safety risks for these subjects. The reality in some study hospitals, she tells me, is that there are a large number of nurses - sometimes up to 1.000 - who might encounter a subject to be included in the trial, and all these 1.000 nurses must all know what to do and how to administer the drug according to the protocol. But with every 1.000 nurses that are added, the risk of one of those nurses not being sure what to do or not administering the test drug correctly increases. Moreover, the more sites included, she explains, the less routine will the staff at the sites have with administering the drug to the subjects, and the chance that precisely those nurses who have previously enrolled a subject in the trial are also on their shift when a new subject comes in is very slim.

Conversely, if the entire trial was carried out in only one hospital with the same staff, the nurses and doctors would obtain a lot of experience with the protocol and with

administering the drug, which would greatly increase the likelihood that the trial was being conducted according to the protocol and that it had not been administered

incorrectly to trial subjects. However, it would also take this one hospital several years to complete the trial. And, as I know from conversations with patent attorneys in the company, in pharmaceutical development, time is valuable.

As one attorney explained to me just after I entered the company, in order to initiate a clinical trial, various approvals from authorities must be sought, and the trial is publicized online. Due to such transparency requirements, many pharmaceutical companies submit their patent applications early in the clinical trials in order to mitigate the risk of others patenting the substance that they are in the process of testing. This, too, is another balancing act, because the patent typically expires after 20 years, and if it takes the company 10 years to complete the clinical trials and get the new drug on the market, then there are only 10 years left to recoup the benefits of the investment.¹⁰⁸ Therefore,

108 The short timespan to earn back what is surely an extraordinary amount of money spent on drug development is an argument that is often used to justify high drug pricing, but this issue lies beyond the scope of this study.

177 the faster a trial can be completed, the more time will be left to the patent, and the more time the company has before cheaper generic products are launched on the market. Conversely, every delay in a clinical trial is patent time lost and therefore money lost.

The choice to include 60 sites rather than the 50 that were initially planned should be seen in this light, Ellie explains. After having started to recruit patients for the study, the clinical trial team realized that recruitment was proceeding too slowly. They decided to add a few extra sites to speed it up.

Moreover, because the national and private healthcare systems differ from country to country, it adds further complexity and insecurity to a trial, the more countries it

involves. To mitigate this risk, the clinical trials team has included only those countries in which they could have at least five sites. Thus, if a country had only three hospitals or clinics that could participate in the trial, this country would be deselected. She explains that in many ways, it has been what she terms ‘a pragmatic trial design’ where the team has assessed what would be possible within the timeframe they had and before the patent expired.¹⁰⁹

The invoking of ‘pragmatism’, I would argue following Lambek (2010a), is a window to ethical practice, and the clinical trials officers’ judgments are no exception. They are faced with weighing

incommensurable elements against each other. Moreover, although the purpose of the

aforementioned GCP guidelines is indeed to protect the humans participating in the trial as well as to ensure that the data collection is valid, complete and well-documented¹¹⁰, the ‘pragmatism’ that Ellie describes also illustrates the space within the GCP guidelines for practical judgment, where the need for speed in the process is balanced against the risk of protocol mistakes and thus data validity, all of which can affect the treatment of ‘subjects’ as well as the company’s revenue at a later stage. The speed of the process, because of the expiration conditions of the patent, whereas mistakes mean that results might not be significant enough, or might not be approved by the authorities if they are deemed too uncertain.

109 Based on field notes from meeting with Clinical trials officer, Denmark, Autumn 2017.

110 http://www.gcp-enhed.dk/en/whatisgcp/

178 Ellie’s situation fits well into Lambek’s (2010a) argument that instead of trying to locate ethics as a fixed object, we must pay attention to actions such as the establishment and recognition of criteria and the exercise of practical judgment (Lambek 2010a:11–12). We see how Ellie describes an ideal for the quality of the study: to conduct it in very few or even in one single site; but that the timeframe of the patent does not allow for this. Moreover, keeping a clinical trial going is also costly in terms of all the internal and contracted resources; continuing work over a prolonged period will add extra costs, and she has to be ‘pragmatic’.

Within this situation, Ellie and her team have judged and deliberated among a number of potential choices. There are the choices to conduct the study within a very limited number of sites versus a very large number of sites and everything in between. The way in which Ellie describes these choices and weighs the different options against each other is an expression of her practical judgment of what is the right thing to do within the pragmatic context of this particular trial. Of course these choices have not been made by Ellie alone. They emerge from a process of recommendations from and conversations between the entire clinical trial team and the corporate governance bodies above them.

Back in the canteen, I ask Ellie why they ended up with close to 60 trial sites when their initial judgment had been that the right balance between speed and risk of protocol deviations¹¹¹ or misunderstandings was 50 sites. She explains that in the USA, in order to approve a new drug on the market, the Food and Drug Administration (FDA) requires a certain portion of the study to have been conducted in the US. There are no formal requirements for how big such a portion must be, but it needs to be somewhat

significant, she explains. At the beginning, they had only two sites in the USA out of 50, and within the clinical trials team as well as within the internal governance bodies above them, this was not deemed enough to meet the FDA’s demands, she explained.

Normally, they would plan for 20% of the sites to be located in the USA in order to live up to the FDA’s requirements. I ask her why it was so important to have the drug approved in the USA, and she replies that it is because the expected earnings in the American market for this particular drug would be considerably higher than on the European

111 ‘Protocol deviations’ is the term used for actual detected deviations (such as a drug administered improperly or at the wrong time) and must be reported as part of trial documentation, as it may have an influence on the results. Here, I refer to all the potential protocol deviations (including non-detected ones) mentioned by Ellie, where a study nurse might have understood the protocol slightly wrong, may lack sufficient skills administering the protocol, etc.

179 market. Therefore, it was necessary to add extra sites in the USA to have the drug

approved there. However, at the same time, there were challenges in recruiting patients in the USA, and they could thus not close a corresponding number of sites in the EU and maintain only 50 sites in total, because that would entail an undesired and costly prolongation of the study.

As seen in the above example, the criteria available for making the right decisions involve elements of (patent expiration) time, cost, potential protocol deviations, future approvals and future potential revenue. In this matrix of choices, little attention is paid to the ‘trial subject’; presumably due to the fact that the trial adheres to GCP and that questions of safety and patient protection a re covered, as argued earlier. With these evaluative criteria in mind, the choices that present themselves are to leave out the USA sites entirely because of low recruitment rates – an option that is rejected because of the potential future earnings from the American market and thus the need for FDA approval on this market.

Another potential choice is to close some of the planned European sites when increasing the American sites and to maintain the 50 sites initially decided upon. This is also rejected because of the costs involved if the trial is prolonged, as this will shorten the time left of the patent. The choice of increasing the number of sites in the USA while maintaining the number in the EU is also available, and as it responds to the requirement to have a significant number of sites in the USA while not affecting the potential future earnings by prolonging the trial time (and shortening the patent time), this ultimately becomes the decision, although 50 trial sites were initially deemed to be the best number.

The practical judgment here is thus a judgment that transcends temporalities, as the potential and predicted future outcomes affect decision-making. In the potential case that the drug succeeds, Ferring wishes to be able to make use of the patent period for as long as possible. Moreover, if the trial should succeed, Ferring likewise wants to be able to get approval from the FDA because of the higher potential revenue in the USA than in other markets. Of course, these potential future outcomes are predicted based on past experiences, and the practical judgment thus takes place at this intersection between past and future. The clinical trials officers’ choices are informed by various experience-based

potentialities, and that is another reason why I define them as a community of practice. They are aware of the pragmatic factors that need to be considered within this community and act accordingly.

As I have highlighted in this example, time, cost, data validity and potential future earnings were significant criteria for judging and deciding the course of action, while the ‘subjects’ involved in the trial were given less attention. I will not assess whether this was ‘the right course of action’. It was the