Multisite Studies Offer a Solution to Recruitment Challenges in Palliative Care Studies

Dear Editor:

Cachexia in advanced cancer is a common source of distress for patients and caregivers. Research is clearly needed to better understand both mechanisms and targets for therapy. The research team in the study by Yennurajalingam and colleagues¹ are to be congratulated for attempting to answer the question of thalidomide's value in cancer cachexia. This type of research is hard and the authors understandably concluded, “Future anorexia-cachexia treatment trials in patients with advanced cancer should use less stringent entry criteria and less exhaustive outcome measures.” We propose an alternative conclusion: Efficacy studies such as the one attempted are crucial, must be carefully conducted, and require multisite studies.

In cancer cachexia, because we know so little about which interventions are efficacious, rigorous explanatory trials are needed. Such trials are difficult to accomplish in a timely way in single sites due to challenges of recruiting sufficient numbers of a carefully characterized cohort of participants in any one location—as these authors experienced. Multisite trials increase the likelihood of recruiting a meaningful sample size. To achieve this, the whole palliative care research community must come together and collaborate—single units will struggle to deliver the complexity and numbers of participants to answer these questions quickly enough. Reducing the stringency of the enrollment criteria such that recruitment is feasible in one center diminishes our capability for understanding efficacy of a particular intervention and risks prematurely dismissing potentially meaningful treatments. In addition to increasing study efficiency through faster recruitment, multisite research delivers a stronger study by facilitating thoughtful involvement of more clinician researchers and providing carefully standardized study operating procedures that can be adopted in a replicable way at each site. It serves as a wonderful training ground for junior investigators. Multisite studies are also more generalizable and deliver the potential collateral benefits of phase III clinical research to a larger number of participants.

Multisite research infrastructure is now becoming available to support and test the good ideas of palliative care researchers. The Palliative Care Research Cooperative (PCRC) and the Australian Palliative Care Clinical Studies Collaborative are examples of multisite initiatives to enhance the rigor of palliative care studies by increasing opportunities for recruitment across multiple sites and creating the infrastructure to conduct standardized, high-quality research studies. Cooperatives of this type will hopefully enable studies like that of Yennurajalingam and colleagues^1–3 to maintain stringent eligibility criteria and at the same time have access to a larger pool of individuals suffering with cachexia, so that effective approaches for their care and management can be identified.