Rethinking clinical trials in the multimorbidity era: the imperative for patient-centered tailored approaches
Ana Isabel González-González et al.
Highlights
• Multimorbidity affects over 50% of older adults, but trials still miss its complexity.
• We call for patient-centered, tailored trial methodologies informed by an international expert workshop.
• The article proposes adaptive designs, relevant outcomes, and co-designed interventions.
• A SPIRIT extension for multimorbidity trials is needed to improve transparency.
Abstract
Background and Objectives
Multimorbidity, the coexistence of two or more chronic conditions, affects about 40% of all adults and over half of adults over 60 years. The complexity of multimorbidity (MM) often renders traditional trial designs inadequate, unable to account for the context of interventions, including the interplay of multiple health conditions in daily life. This gap reduces the generalizability and applicability of their results.
Methods
This commentary aims to review the current state of trials targeting or involving patients with MM. Highlighting current limitations and drawing on insights from an international dedicated workshop in Bielefeld, Germany, we identify an ongoing and pressing need for innovative, patient-centered approaches to their design and conduct.
Results
We propose a shift toward more holistic and integrative experimental approaches, including developing interventions tailored to the characteristics and needs of patients with MM, establishing relevant outcomes, and enhancing data collection and process evaluation. We specifically advocate for adaptive trial designs, prespecified subgroup analyses, and the incorporation of patient-reported outcomes and experience measures such as burden of care to ensure that research is both comprehensive and reflective of the needs of patients living with MM, their caregivers, and of the clinicians participating in their care. Ethical considerations are discussed in our commentary as well, emphasizing the importance of patient safety, data protection, and informed consent. Finally, we call for the development of specific reporting guidance, such as a SPIRIT extension tailored to MM trials, to help researchers adapt standard protocols to the complex and heterogeneous reality of this population.
Conclusion
This commentary aims to bridge the gap between research and practice, fostering the development of effective interventions that improve patient outcomes and enhance the quality of care for patients living with MM.
What is new?
Key findings
• Traditional trial designs are poorly suited to the realities of MM. This paper outlines methodological and ethical priorities for patient-centered, adaptive trial design.
What this adds to what is known?
• Integrates international expert consensus into actionable guidance for MM trials, including adaptive, mixed-methods, and co-designed approaches.
What is the implication and what should change now?
• Researchers should adopt flexible, proportionate, and context-sensitive designs and develop dedicated reporting guidance (eg, a SPIRIT extension) to ensure relevance and transferability.
Table 1
Essential actions and considerations necessary for trustworthy, useful, and generalizable trials in effective MM research
| SPIRIT checklist item | Explanation of SPIRIT item | Workshop conclusions and actions for multimorbidity research |
|---|---|---|
| Trial design | Description of the trial’s structure and methodology. | Use adaptive trial designs with oversight from an independent committee. Report adaptations transparently. |
| Study setting | Description of locations and settings where the trial is conducted. | Select care settings that reflect real-life multimorbidity care, including fragmented services and support networks. Use PROGRESS-Plus to guide equity. |
| Eligibility criteria | Criteria for patient selection, including inclusion and exclusion factors. | Include diverse patients with cognitive, physical, or social complexity. Consider SES, health literacy, and caregiver support. |
| Interventions | Detailed information on interventions for each group to allow replication. | Co-design interventions with patients and professionals. Ensure adaptability. Use structured frameworks for description. |
| Outcomes | Primary and secondary outcomes to be measured, including their relevance and timing. | Prioritize outcomes important to MM patients (function, QoL). Use sensitive PROMs and PREMs. Include process measures. Align with causal pathways. Involve patients. Refine existing COS. In addition, embed qualitative indicators to capture patient and caregiver experiences, contextual factors, and perceived changes in care processes complementing quantitative measures. |
| Data collection methods | Plans for how and what data will be collected to ensure quality and relevance. | Prioritize meaningful outcomes, even beyond routine data. Reduce burden via PPI. Support diverse needs. Use guided PROMs. Avoid ‘scope creeping’. Train staff and adapt. Include process evaluations to assess fidelity and context using GRIPP. Use community-based strategies for inclusive engagement. Combine quantitative and qualitative methods to ensure a comprehensive understanding of intervention mechanisms (theory of change) and contextual influences. |
| Statistical methods | Plans for analyzing collected data, including any additional or subgroup analyses. | Use prespecified subgroup analyses reflecting clinical and demographic diversity. Assess credibility with tools like ICEMAN. |
| Harms | Plans for identifying, recording, and addressing adverse events or other unintended effects. | Monitor QoL, function, and prescribing. Use proportional risk management. Ensure data protection, especially with digital tools. |
| Ethics and dissemination | Approaches for ethical approval, amendments, and sharing results with stakeholders. | Apply proportional oversight. Minimize burden. Share results transparently with patients and stakeholders. Safeguard data privacy. |
