Clinically Meaningful Inclusion of Participants in Clinical Trials. David Hickam, MD, MPH Washington, DC April 9, 2015

Transcription

1 Clinically Meaningful Inclusion of Participants in Clinical Trials David Hickam, MD, MPH Washington, DC April 9, 2015

2 Key Questions for this Presentation What are the important features of patient centered outcomes research (PCOR)? What are some promising strategies for ensuring broad patient participation in clinical trials? Stakeholder engagement Pragmatic study design Can data analysis compensate for problems with participation rates?

3 About PCORI An independent research institute authorized by Congress through the Patient Protection and Affordable Care Act. Funds comparative clinical effectiveness research (CER) that engages patients and other stakeholders throughout the research process. Seeks answers to real-world questions about what works best for patients based on their circumstances and concerns.

4 Some of PCORI s Priorities Patient-centered clinical research Research done differently Value of interdisciplinary teams Research in real world settings Outcomes that are important to patients Dissemination of best practices Research results that are applicable to broad population groups

5 First Steps in Developing New Comparative Effectiveness Research Understand the choices made by patients and clinicians Which clinical options are realistically available to patients? Define the important patient sub-groups Recognize disparities and their sources Define the outcomes (benefits and harms) that are important to patients Benefits Harms

6 Engage Stakeholders/Patients to Help Design the study to integrate with routine clinic/office operations minimize disruption to participant s daily routine Refine recruitment strategies and proactively deal with recruitment issues Participate in data monitoring and safety activities Capitalize on existing resources (e.g., electronic health records, claims databases, networks) to collect study outcomes information

7 Pitfalls in Patient and Stakeholder Engagement Researchers are inexperienced in building and managing interdisciplinary teams Partners are not well integrated into management of the study Kept at arm s length Meetings are overly formal Investigators reluctant to acknowledge problems Partners do not have sufficient access to the clinical sites Partners do not have enough time/resources

8 Pragmatic Clinical Trials Developed as an alternative to conventional tightly controlled clinical trials (also referred to as explanatory trials ) Advocated as a way to evaluate the effectiveness of clinical interventions in real-world settings Minimize exclusion criteria that are a barrier to participation by some patients Require partnerships with clinical delivery systems

9 Features of Pragmatic and Conventional (Explanatory) Trials Pragmatic Trials Explanatory Trials Participant Eligibility Participant follow-up All patients with the condition are invited to enroll Performed only at regular clinic visits Many exclusion criteria Specially scheduled visits at designated intervals Clinical setting All clinics in the system that serve patients with the condition Specialized clinics with specially trained providers Thorpe et al.. JCE 2009; 62:464.

10 Considerations in the Use of Pragmatic Designs Type of interventions Treatments that are in common use Can be complex interventions Type of comparator Suitable approach for head to head comparisons Usual care often used, but has limitations For placebo comparisons, a pharmacy link is needed Type of outcomes Easiest approach is to use measures derived from EHR Lab results, BP, weight, etc. PRO s are feasible, but blinding can be a problem

11 What are Limitations of the Pragmatic Approach? Often does not provide sufficient outreach to patients who are uninsured or have other problems with access to care Researchers tend to partner with university clinics rather than broad-based community or rural sites Outcomes often have lower precision related to timecourse and missingness, resulting in loss of power

12 PCORI Initiatives that Focus on Learning about Best Practices for Trial Recruitment CER Methods Program Evaluating novel approaches to engagement Informed consent Disparities Research Program Navigation Literacy/numeracy barriers

13 Statistical Approaches for Analyzing Heterogeneity of Treatment Effects Stratified analyses Separate analysis for each important sub-group Serious risk of spurious findings (both type 1 and type 2 errors) Multivariate analysis with interaction terms Much lower risk of spurious findings Lacks power (need to increase sample size by factor of 4) What to do All such analyses should be considered exploratory

14 We Work to Improve Research Methodology In any study, methods matter. That s why we ve developed methodology standards that all research should follow, at a minimum. Methodology Standards: 11 Broad Categories Formulating Research Questions Patient-Centeredness Data Integrity and Rigorous Analyses Preventing/Handling Missing Data Heterogeneity of Treatment Effects Data Networks Data Registries Adaptive and Bayesian Trial Designs Causal Inference Studies of Diagnostic Tests Systematic Reviews

15 Summing Up: Which Strategies are Likely to be Successful for Improving Participation in Clinical Trials? Patient and stakeholder engagement is an important emerging strategy Can prevent and correct problems Requires commitment of investigators and experience with interdisciplinary approaches The pragmatic approach can facilitate recruitment Minimizes exclusion criteria Broadens base of clinical sites Can reduce the precision of outcome measures Post hoc analyses of sub-groups are always exploratory

16 Join Us at PCORI.org