Clinical Studies Continuum What features are special with regard to Comparative Effectiveness and Patient Centered Outcomes Research

Definition and Purpose of CER CER is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers and policy makers to make informed decisions that will improve health care at both the individual and population levels.

Distinguishing Characteristics of CER Informing specific clinical or policy decision Comparing at least two approaches or interventions Describing results at the subgroup level, where possible Measuring benefits in real-world populations in real-world clinical situations Applying appropriate methods and data sources

Poll Everywhere Question What is a reason why the US needs of comparative effectiveness research? Current biomedical studies often have restricted patient populations. Current biomedical studies often have very tightly supervised protocols that are hard to duplicate in practice. The questions asked in current studies do not answer the real decision-making needs of clinicians and patients. All of the above.

Definition and Purpose of PCOR From PCORI: Patient-Centered Outcomes Research (PCOR) helps people and their caregivers communicate and make informed healthcare decisions, allowing their voices to be heard in assessing the value of healthcare options.

This research answers patient-centered questions, such as: “Given my personal characteristics, conditions, and preferences, what should I expect will happen to me?” “What are my options, and what are the potential benefits and harms of those options?” “What can I do to improve the outcomes that are most important to me?” “How can clinicians and the care delivery systems they work in help me make the best decisions about my health and health care?”

Poll Everywhere Question All comparative effectiveness research is also patient-centered outcomes research. True False Not all CER is PCOR

Once you have an articulated question The study design will: Connect the specific aims, research question, and hypotheses through the approach by identifying the study population, collecting appropriate data, and using the best tools to analyze the data.

Major steps in final design/approach Research Methods/Study Design Study Population Measures Data Collection/Procedures Data Management Statistical Analyses Statistical Power

Threats to validity Classic texts by Campbell and Stanley (1963 and 1966) These threats may apply to both experimental and quasi- experimental designs You must account for these in the design of your study and in the analysis plan

Threats to validity: 8 identified History Maturation Testing Instrumentation Statistical regression Selection Experimental mortality Diffusion of treatments

Threats to validity: 8 identified History Events, other than the experimental treatments, influence results.

Threats to validity: 8 identified Maturation During the study, changes occur within subjects, such as psychological changes

Threats to validity: 8 identified Testing Exposure to a pretest or intervening assessment influences performance on a posttest.

Threats to validity: 8 identified Instrumentation Testing instruments or conditions are inconsistent; or pretest and posttest are not equivalent, creating an illusory change in performance.

Threats to validity: 8 identified Statistical regression Scores of subjects that are very high or very low tend to regress towards the mean during retesting.

Threats to validity: 8 identified Selection Systematic differences exist in subjects’ characteristics between treatment groups.

Threats to validity: 8 identified Experimental mortality Subject attrition may bias the results.

Threats to validity: 8 identified Diffusion of treatments Implementation of one condition influences subjects in another condition.

A continuum of clinical studies (not exhaustive of all designs) Case study (clinical) or case series Observational study – no control Observational study – with control “Natural” experiments, e.g., Oregon-Medicaid Pre-post designs Experimental designs Individually randomized controlled trial Cluster or group randomized controlled trial Stepped wedge design

Valid Scientific Evidence 21 CFR 860.7 (Device Regulations) Includes Well-controlled investigations Partially controlled studies Studies and objective trials without matched controls Well-documented case histories Reports of significant human experience with a marketed device

Differences Between Efficacy and Effectiveness Studies   Efficacy study Effectiveness study Question Does the intervention work under ideal circumstance? Does the intervention work in real-world practice? Setting Resource-intensive ‘ideal setting’ Real-world everyday clinical setting Study population Highly selected, homogenous population Several exclusion criteria Heterogeneous population Few to no exclusion criteria Providers Highly experienced and trained Representative usual providers Intervention Strictly enforced and standardized; No concurrent interventions Applied with flexibility; Concurrent interventions and cross-over permitted

What’s Unique about CER Direct head-to-head comparisons of competing treatments, prevention modes, or health system interventions (or variations) Topics oriented to clinical decision-making Tests, treatment, stategiess for prevention, care, delivery and monitoring. Study design and endpoints relevant to a wide group of stakeholders: Patients, clinicians, purchasers, policy makers Study populations should be representative of clinical practice.

What’s Unique about PCOR The stakeholder, especially patient voice, is heard throughout the study – from conception, to design, through conduct, and dissemination and implementation The outcomes are centered around what is important to patients. Note: patient-centered outcomes come in a variety of measures and are not synonomous with patient reported outcomes.

What to Consider in Study Design related to CER and PCOR Consider “real-world” populations and “real- world” clinical situations Ensure the comparison is between legitimate alternatives Ensure the data will answer the question with a focus on the clinical or health care system decision to be made and that the results are translatable to your organization Ensure, where possible, all stakeholders are represented throughout the study process