Community-Based and Cluster-Randomized Studies –‘Pragmatic’ Approaches for Life Cycle Evidence? Florian Eichmann, PhD Principal Scientific Affairs and Real World Evidence, Late Stage inVentiv Health

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Community-Based and Cluster-Randomized Studies –‘Pragmatic’ Approaches for Life Cycle Evidence? RCT- Expl. Trial ….a third way….? Non-Interv. Study Protocol driven Protocol AND usual care Usual Care Scheduled visits Observed visits Case Report Form (CRF) CRFs Data Collection Form (DCF) “Efficacy” Effectiveness “Effectiveness” Blinded unless not feasible Usually unblinded Unblinded Follow-up for proxy endpoints Real life endpoint follow-up Follow-up for real life endpoints Homogeneous ‘ideal’ patients Heterogenous ‘real’ patients Heterogeneous 'real' patients ‘Experienced’ investigators Everyday practicioners ‘Everyday’ practitioners ‘Motivated’ patients Usual patients ’Usual' patients / subjects Pharmacological differences (Clinical Research) ‘Pharmacological’ AND ‘Management’ differences ’Management’ differences (Health Care Research) Can it work…if given? Does it work...better? Does it work … if offered? Internal validity focus Internal AND external validity External validity focus All phases, focus on II, III Usually Late Stage (disease observation) CAUSALITY—Compare two or more groups (control heterogeneity) CAUSALITY—Compare two or more groups ASSOCIATION—matching, multiple regression, propensity score, instrumental variables .. © 2015 DIA, Inc. All rights reserved.

Community-Based and Cluster-Randomized Studies –‘Pragmatic’ Approaches for Life Cycle Evidence? Increasing discussion on pragmatic study types But do we also see more of these studies? Medline search Qualitative review Results © 2015 DIA, Inc. All rights reserved.

Annual Medline Publication Title Hits © 2014 DIA, Inc. All rights reserved.

Medicinal Product Studies among Medline Title Hits © 2014 DIA, Inc. All rights reserved.

Medicinal Product Studies – Qualitative Study Design N Recent Medicinal Product Title Hit Studies Pragmatic 5 asthma, skin infection, pneumonia, rheumatoid arthritis, osteoarthritis Community-based 3 pneumonia, myeloma, colorectal cancer Two studies used subject based randomization, One study was observational. Cluster-randomized 1 vaccines All studies studies analyzed medicinal products with regard to clinical and/or patient reported and economic outcomes in real life situations versus standard therapy or an active comparator. No reference to life cycle evidence © 2014 DIA, Inc. All rights reserved.

Conclusions & Outlook Growing numbers of cluster-randomized and pragmatic studies Few studies on medicinal products Various indications Many studies on public health or non-medical or complementary medicine Practical use for life cycle evidence is still limited Most studies still use non-interventional designs Strategic, financial, regulatory, and educational reasons Modifications e.g. “stepped wedge” designs to overcome hurdles © 2014 DIA, Inc. All rights reserved.

Thanks for your attention! Poster Nr. 3 florian.eichmann@inventivhealth.com © 2015 DIA, Inc. All rights reserved.