Competing for patients: an ethical framework for recruiting patients with brain tumors into clinical trials

Abstract

With more rapid advances in potential treatments for brain tumours, the number of clinical trials for brain tumour patients is rising. In the context of the challenges of recruitment and enrollment of patients with brain tumors, the dichotomy between the paucity of subjects and abundance of clinical trials creates a unique ethical dilemma, whereby a single patient may be eligible for several studies. Here, we identify and present three approaches for recruiting and enrolling patients who may be eligible for several trials. The ethical implications of the full disclosure, paternalistic, and random approaches are discussed. The full disclosure approach presents information to patients regarding all ongoing concurrent trials, allowing them to make an informed decision, while the paternalistic approach allows the healthcare providers to select the trial for which they believe the patient is most suitable. These introduce the biases into circumstances where equipoise is necessary and risk selection bias in study design. The random approach randomly allocates patients to each trial, which may erode patient autonomy and decrease trial enrollment. Brain tumor patients comprise a vulnerable population and it remains incumbent on healthcare providers to maintain the highest ethical standards when approaching them for clinical research. Changes in clinical trial design are required to mitigate the conflicts created by competition for patients. Keywords Brain tumors Á Clinical trials Á Ethics Á Patient enrollment Á Patient recruitment Illustrative caseA previously healthy 50 year old female, recently diagnosed with non-small cell lung carcinoma presents to a multi-disciplinary neuro-oncology clinic for evaluation of a single 1.5 cm metastasis in the right temporal lobe, discovered on screening magnetic resonance imaging (MRI). Standard treatment options would include surgical resection with adjuvant whole brain radiation therapy (WBRT), WBRT with radiosurgery boost or WBRT alone. She is also eligilible for two clinical trials offered at the hospital at which she is receiving treatment. One investigates the efficacy of a small molecular tyrosine kinase inhibitor in combination with radiosurgery and one investigates the inclusion of WBRT with radiosurgery treatment. The multi-disciplinary team meets to inform the patient of the institutional standard-of-care treatments and the two clinical trials available. They are faced with the challenge of effectively, fairly and ethically presenting the treatment options available.

When clinical trials compete: prioritising study recruitment

“…This gives it an important advantage over competing approaches. Allowing patients or clinicians to choose between trials, as some advocate,2 6 will not address or minimise the problem of competing studies, since patients and clinicians are not responsible for the completion of studies and will (and perhaps should ) base their choice on considerations other than making sure that the institution's prioritised trials recruit enough to complete. Likewise, randomising participants between competing studies (as per ref.…”

“…A second approach denies that there is any obligation to offer potential participants a choice between competing trials and instead leaves the choice up to clinicians , who typically offer trials based on their own estimation of a trial's therapeutic potential or other, more idiosyncratic factors (such as the level of investment of the clinician or department chief in different studies and what they have to gain from prioritising some over others) 2. A third option, motivated by avoiding bias and ensuring scientific integrity, is to employ a randomising procedure to decide which trials to offer individuals, similar to the use of randomisation to allocate participants to different arms within individual studies 4.…”

Pediatric clinical trials

“…This situation where an individual patient could be eligible for enrollment for several trials creates a unique ethical dilemma. [45] The researchers have to choose from one of the three approaches: Full disclosure, paternalistic and random assignment. The researcher taking the full disclosure approach provides information about all ongoing concurrent trials, allowing parents and participants to make the decision regarding the trial to enroll with.…”

“…This strategy may erode patient autonomy. [45] Pediatric treatment outcome research focusing on the physical and mental health of children living in rural areas is limited, despite the immense need. Challenges to recruitment include researchers being viewed as outsiders by rural community members, population size and density of rural communities, unique aspects of rural culture and higher rates of poverty and lower educational achievement in rural areas.…”

Institutions as an ethical locus of research prioritisation

“…Absent a centralised mechanism between funders to ensure optimal distribution of trials between sites, trials prioritised at the level of funder may still compete with each other for participants at the site level. Indeed, there is ample evidence that intra-institutional competition between trials is a reality, particularly in certain specialisations such as brain tumour and stroke research 7 8. A recent survey, for example, found that 92% of StrokeNet sites have policies in place for determining which trial should be offered to patients who are eligible for more than one study, confirming that competing trials are common in this space and the importance of prioritisation at the institutional level 9.…”