The PRIME-NL study: evaluating a complex healthcare intervention for people with Parkinson's disease in a dynamic environment

Background: An innovative, integrative care model for people with Parkinson (PRIME Parkinson) has gradually been implemented in a selected region of the Netherlands since 2021. A prospective evaluation of this model (PRIME-NL study) was initiated in parallel, spanning the year prior to implementation (baseline) and the implementation period. Following publication of the original study protocol, the COVID-19 crisis delayed implementation of the full PRIME Parkinson care model by two years and hampered the recruitment of study participants. Objective: To describe which methodological adjustments were made to the study protocol because of these developments. Methods: We compare various outcomes between a region where PRIME Parkinson care was implemented (innovation region) versus the rest of the Netherlands (usual care region). We use healthcare claims data of virtually all people with Parkinson in the Netherlands and annual questionnaires in a representative subsample of 984 people with Parkinson, 566 caregivers and 192 healthcare professionals. Four major methodological adjustments had to be made since publication of the original protocol. First, we extended the evaluation period by two years. Second, we incorporated annual process measures of the stage of implementation of the new care model. Third, we introduced a real-time iterative feedback loop of interim results to relevant stakeholders. Fourth, we updated the statistical analysis plan. Discussion: This manuscript provides transparency in how the design and analyses of the evaluation study had to be adapted to control for external influences in a dynamic environment, including eruption of the COVID-19 crisis. Our solutions could serve as a template for evaluating other complex healthcare interventions in a dynamic environment. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research is part of the PRIME project, which was funded by the Gatsby Foundation [GAT3676] as well as by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships. The Center of Expertise for Parkinson & Movement Disorders was supported by a center of excellence grant by the Parkinson Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The PRIME-NL study has been approved by the Ethical Board of the Radboud University Medical Center, reference number 2019-5618. The study has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Participants signed a digital or written informed consent before inclusion in the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors