How informed is declared altruism in clinical trials? A qualitative interview study of patient decision-making about the QUEST trials (Quality of Life after Mastectomy and Breast Reconstruction)

Randomised controlled designs for trials of different treatments (RCTs) are essential to minimise selection bias and ensure that treatments are based on the best possible evidence. However, many trials do not recruit the desired participant numbers required to meet study objectives, despite often citing altruism as their motivation for participating. The statistical power of the results then becomes compromised or the costs through extensions to the recruitment period are increased [1]. In order to maximise the rates of trial participation whilst ensuring patients can make their decisions based on a clear understanding of what is involved, it is imperative to understand factors affecting motivation and patient decisions around participation and non-participation in trials.

Altruism, defined as ‘acting with an unselfish regard for others’ , has been identified as a potentially important factor in patient’s decision-making as to whether or not to consent to trials. Altruistic motivations in healthcare trials include patients’ desire to help others with the same condition and contribute to progressing medical knowledge [2]. However, factors other than altruism may be motivating factors in patients’ decisions; although cancer trial participants within drug-intervention studies commonly reported that altruism contributed to their decision to enrol, they also expected to receive medical benefits [2‐4].

Current studies evaluating the levels of trial participation are methodologically limited; involving either healthy participants responding to hypothetical scenarios in analogue studies; and by focusing exclusively on those patients consenting whilst ignoring those who declined [5]. Previous surveys are difficult to interpret as respondents were rarely asked to make a choice between self-interest and altruism, typically reporting both motivations without exploring how these motivations were weighted [4].

Importantly, regulation of most new drugs and devices mean that they are available to patients only if they agree to participate in a clinical trial, making it difficult to disentangle their motivations toward science and themselves. Many agree to participate in the hope of receiving experimental treatment as well as contributing to medical knowledge. Different trial designs include control arms which could be a standard treatment or a placebo (even sham surgery in some cases), which compound the difficulty in interpreting results about motivation. [6, 7]. Recently, McCann et al. [8] conducted a qualitative study, embedded in a ‘patient-preference’ trial (in which patients could either select their preferred treatment or accept random allocation of those treatments). Results suggested that people rarely participate in trials out of purely altruistic reasons, and often require some perceived personal benefit from being randomised in a trial.

Our study investigates what is often regarded as a socially desirable, yet unexplored, response of altruism. To better understand how patients weigh altruism in their decision-making about participating in clinical trials we also examined any stated personal treatment preferences and understanding of fundamental aspects of RCTs, such as randomisation and clinical equipoise. The effects of altruistic motivations on decisions about participation might be moderated by misperceptions of randomisation, equipoise or by treatment preferences [7]. For example, patients may be motivated to participate because they believe that the research will benefit others but decide against taking part because they have not understood the attributes of an RCT. On the other hand, a decision to participate in the trial might seem to be purely altruistic if the patient has a strong personal treatment preference and their decision to participate in the trial is made with a full understanding that, through randomisation, they may not receive the preferred treatment that they could have selected outside the trial.

The Quality of Life after Mastectomy and Breast Reconstruction (QUEST) trials (Cancer Research UK funded: C10318/A10077, reference Trial A ISRCTN: 38846532, Trial B 92581226) comprised two parallel feasibility phase III randomised multicentre trials to assess the impact of the type and timing of latissimus dorsi (LD) breast reconstruction on health-related quality of life (HRQL) when post-mastectomy radiotherapy is unlikely (Trial A) or highly probable (Trial B) [9]. All women with either invasive breast cancer or ductal carcinoma in situ requiring mastectomy were eligible (Fig. 1) [9]. Surgical treatment arms comprised a standard care arm versus a less practiced new intervention arm in both trials. The standard of care was implant-assisted LD breast reconstruction in Trial A, and staged-delayed (two-stage) extended autologous LD breast reconstruction in Trial B. Despite its pragmatic design, the LD breast reconstruction techniques were well established in the UK, and were potentially available to patients outside the trial.

The QUEST Perspectives Study (QPS) was an embedded study evaluating the perceptions of patients and healthcare professionals on randomisation (views on decision-making and subsequent experiences) to inform QUEST trial processes and enhance ongoing recruitment and patient acceptability. In the current analysis, we examined patients’ views about altruism, as a factor in their decision to participate (or not) in a clinical trial, in the context of: (1) their understanding of randomisation (the rationale and trial process); (2) their comprehension of clinical equipoise related to the impact of health-related quality of life (HRQL) on the types and timings of immediate LD breast reconstruction; and (3) their perceptions of and preferences towards the treatment options available to them both before and after randomisation.

This study explores the meaning of expressed altruism when patients are invited to participate in a surgical RCT where the primary outcome measure comprised HRQL and where the new surgical interventions were available outside the trial. This study illustrates how patients weighed up different motivations, after initially expressing altruism, to decide whether or not to accept the trial, and reports how informed those motivations were, given the patients’ understanding of the trial and the treatment options available, and any stated personal preferences.

Altruism was expressed initially by both acceptors and decliners of the QUEST trials. These initial motivations were often modified by understanding the trial and individual beliefs about the surgical options, and, in many cases, were overridden by personal interest according to treatment preference. Moreover, some acceptors who were in ‘clinical equipoise’ seemed simply not to mind being randomised. Altruism was still expressed by some who had accepted randomisation despite having a treatment preference. All but one of these patients were randomly allocated to their treatment preference and so did not have to ‘test’ their declared altruism afterwards by potentially withdrawing after randomisation.

Our findings somewhat corroborate results from a recent qualitative study suggesting that altruistic motivations amongst those who accept randomisation are often tempered by self-interested motivations in various ways even when they are in a state of clinical equipoise [8]. However, it was unclear how informed these motivations were. Some patients perceived benefits of taking part in the QUEST trials, such as avoidance of making a difficult choice between surgical options, gaining an element of control by deciding to participate or perceived greater input from the healthcare team, and their altruistic motivations were conditional upon this. There is some, albeit weak evidence from comparative studies suggesting that patients may do better within trials on similar treatment to those outside of trials [12]. This study further explores conditional altruistic motivations by cross-referencing the patient's declared motivations with their actual decisions and their understanding of the trial. Only one patient in our study consented against her declared treatment preference, but she did not fully understand the trial and it was unclear whether her decision to take part was an authentic choice to be altruistic (i.e. one that reflects the true preference of the individual).

Our finding that patients did not always fully understand the trial and its alternatives (both acceptors and decliners) concurs with previous work [13]. There appeared to be misunderstanding of how the treatment option was decided if they entered the trial and, related to this, some participants did not hold views consistent with ‘clinical equipoise’. For decliners, misunderstanding randomisation and equipoise may not be the sole factors responsible for them choosing not to take part as they had strong preferences for a particular surgical option or they wished to make the decision by having control themselves. Findings from this study were regularly reported to the QUEST Trial Management group and the Trial Steering and Data Monitoring Committee whilst the trials were running, and helped inform ongoing recruitment strategies. A standardised trial information checklist was an early by-product of this study 3 months after trial commencement. The use of this checklist by the research nurse within trial consultations was standardised across all centres and was instrumental in attempting to balance expressed patient preferences [9].

We did not include all those respondents in QPS (namely those who did not express any altruism) in our present analysis because there would have been no way of weighing up different motivating factors in the unique way QUEST allowed. While an expression of self-interest alone does not necessarily exclude all altruistic motivation, we were primarily interested in those situations in which self-interest and altruism led to contradictory decisions to help gauge the strength of those motivations.

The challenges of surgical trials are well described by Cook et al. (2015) with recommended trial designs including a feasibility phase and embedding qualitative research to inform trial processes [14]. As the first multicentre trials in this setting, the QUEST feasibility trials showed overall patient acceptability rates of 19 % (17 out of 88) in Trial A and 22 % (8 out of 36) in Trial B, respectively over 18 months of recruitment [9].

The findings from this study should be considered in light of its limitations. The interviews were conducted after surgery, and at least a month after the women had made the decision whether or not to accept randomisation. In addition to potential difficulties with accurate recall, it is possible that initial preferences and perceptions were modified as a result of the outcome of randomisation (for acceptors) and post-surgery experiences. Furthermore, the QUEST trials were surgical RCTs, comparing the impact on HRQL of different types and timing of LD breast reconstruction. In addition, the treatments offered in the trial, while available outside the trial, may not always have been offered to patients making the trial a ‘quasi-preference’ trial. The findings from the current study may not be generalizable to other RCTs attempting to recruit from different patient populations, or to evaluate the efficacy of a novel drug treatment against either an active or placebo control, and under different conditions.

Nevertheless, the knowledge gained from this study provides valuable insight that can inform and refine attempts to recruit participants to future RCTs. In particular, information given to patients at the time of consent should clarify the potential benefits of trial participation. The dedicated trial consultation should be led by non-biased healthcare professionals using standardised informed consent where iteration of pros and cons may change/balance patient preferences and perceptions. Evaluation of the patient’s understanding of information as this pertains to randomisation should be routinely assessed to ensure that any expressed altruism is based on truly informed consent. In addition, more research is needed in this area to explore the limits to conditional altruism once patient understanding of trials has been improved in practice. For example, it is not yet clear how perceiving beneficiaries of the trial influences feelings of altruism. Currently, patients are often simply told - vaguely - that the trials to which they are invited to participate in, are designed to benefit patients in the future. This futuristic expectation risks undermining the fundamental precepts of good informed consent, where the patients’ understanding of the rationale and benefits of trial participation are key goals in current trial recruitment. Recommended testing of patient’s understanding of informed consent should be an integral part of feasibility and pilot phase studies within RCTs.

This study makes a valuable and unique contribution to the understanding of the factors influencing patients’ decision whether or not to enter a surgical RCT where the treatment options may be preference-sensitive, despite being technically established and poorly evidenced in terms of patient-reported HRQL. By employing qualitative methods and thereby avoiding some of the limitations of previous research in this area, we have highlighted how different motivations, including altruism, were evaluated by the participants in the context of their understanding of the trial and randomisation. Although both acceptors and decliners of the QUEST trials initially expressed altruistic motivations, these were often revised or outweighed by other factors related to the participants’ own interests and perceptions.