Table 1.
Lessons learned from AD research for PD early disease modification and prevention trials
| Lessons learned from AD research for PD trials | |
|---|---|
| Target population | A combination of early clinical features associated with PD and (biological) risk factors could be used as recruitment criteria, because disease progression is too advanced in people who already have PD and (biological) risk factors on itself have not enough predictive value |
| If the intervention targets abnormal aggregation of a putative causal protein for which an accurately measurable biomarker exists, this biomarker status should be adopted in the eligibility criteria | |
| Disclosing at-risk or early disease status | Apply risk terminology in communication towards research participants rather than a ‘diagnosis’ of prodromal PD |
| Legal safeguards are required to protect participants against privacy violation and discrimination based on risk status | |
| Changes in research disease criteria may tacitly impact clinical practice | |
| Pre-trial evidence for prevention trials | Consider targeting several putative pathological processes simultaneously—thereby not relying too heavily on one potential trigger of the pathophysiological process, provided that the underlying evidence is sufficiently supported by pre-trial evidence |
| Recruitment strategies | Transnational recruitment registries with clinical and biomarker information may tackle current recruitment issues, but are subject to several ethical challenges |
| Outcome measure selection | More sensitive outcome measures may increase the chance of finding a clinical intervention effect, but can only serve as proof of concept if not directly translatable into a clinically relevant effect |
| Immunotherapy may have adverse effects and requires continued scrutiny, also in phase 3 trials | |
| Advancing to phase 3 trials | Use sub-group analyses guidelines to prevent over-interpretation of post hoc analyses in phase 2 trials that lead to misleading expectations for phase 3 trials |
The manuscript does not contain clinical studies or patient data