Approach to Therapeutic Recreation Based Clinical Research Outcome

Measures

PROFESSOR PEIVAND PIROUZI, PH.D., M.B.A.

SENECA COLLEGE OF APPLIED ARTS AND TECHNOLOGY

TO R O N TO, O N TA R I O, C A N A D A

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Treatment Benefit

Treatment benefit is demonstrated by evidence that the treatment has a positive impact on a concept of interest:◦ How long a patient lives

◦ How a patient feels or functions in daily life

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Purpose of Outcome AssessmentTo determine whether or not a drug has been demonstrated to provide benefit to patients

A conclusion of treatment benefit is described in labeling in terms of the concept of interest, or the thing measured by the outcome assessment

One of the most important aspects of drug development is how that benefit is measured

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Types of Outcome Assessments in Therapeutic Recreation

Increased Quality of Life

Clinical outcome assessments (COAs) ◦ Patient-reported outcomes (PROs)

◦ Clinician-reported outcomes (ClinROs)

◦ Observer-reported outcomes (ObsROs)

◦ Performance outcomes (PerfOs)

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Evidence of Treatment BenefitDirect evidence of treatment benefit is derived from studies with endpoints that measure survival, or how patients feel and function in daily life

Indirect evidence of treatment benefit is derived from studies with endpoints that measure other things that are related to how patients live better, feel or function

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Direct

Evidence

Evidence Continuum

Direct Verses Indirect Evidence of Treatment Benefit

Indirect

Evidence

Evidence of Treatment Benefit (Proximal to Distal)

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Social functioning

General

psychologicalfunctioning

Proximal diseaseImpact concepts

Distal diseaseImpact concepts

Relatedfunctioning

Related

Signs/symptoms

Disorder-

definingconcepts

Health-relatedquality of life

Disease impact on general life concepts

Satisfaction

withhealth

Core signs,

symptoms

or

decrements in functioning

Additionalfunctioning

Additional

Signs/Symptoms

General

physical functioning

Productivity

Health status

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Evidentiary Standards to Document Treatment Benefit

Documented by “Substantial evidence” (21 CFR 201.56(a)(3))

Evidence from “Adequate and well-controlled clinical trials”

The methods of assessment are “well-defined and reliable” (21 CFR 314.126)

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When is a Clinical Outcome Assessment Adequate for use?

Regulatory standard: measures are well-defined and reliable◦ Empiric evidence demonstrates that the score quantifies the

concept of interest in the targeted context of use

What does this mean?◦ This means measuring the right thing (concept of interest), in

the right way in a defined population (targeted context of use), and the score that quantifies that ‘thing’ does so accurately and reliably, so that the effects seen in the outcome assessment can be interpreted as a clear treatment benefit.

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Good Measurement Principles to Use in Therapeutic Recreation Studies

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Defines good measurement principles to consider for “well-defined and reliable” (21 CFR 314.126) PRO measures intended to provide evidence of treatment benefit

All COAs can benefit from the good measurement principles described within the guidance

Provides optimal approach to PRO development; flexibility and judgment needed to meet practical demands

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Well-defined and Reliable

The tool adequately measures the concept of interest in the context or clinical setting of interest

To assess this, we review the tool’s measurement properties:◦ Content validity

◦ Construct validity

◦ Reliability

◦ Ability to detect change◦ Information to support interpretation of change

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What is Content Validity

Are we asking the right questions in our assessments?

Do clinical trial participants consistently interpret and understand the questions on the PRO assessment?

What does the score of the questionnaire represent?

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Thinking about Meaningful Change

How much change is meaningful?

Roadmap to Patient-Focused Outcome Measurement in Clinical Trials

Intended to illustrate how one might embark upon a sound, orderly, instrument selection or development pathway, beginning with the clinical context in which the instrument is intended to be used.

The graphic here is meant to help identify the types of things that might be considered in order to improve the ability of an outcome assessment to accurately measure treatment benefit.

◦ Most assessment tools are a bit less orderly in their development

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Defining Context of UseEach of the following variables can impact the adequacy of a COA to support a claim:

Disease definition including, if appropriate◦ Disease subtype

◦ Disease severity

◦ History of previous treatment

Patient subpopulations◦ Patient demographics

◦ Reporting ability

◦ Culture and language

Clinical trial design and objectives◦ Endpoint positioning

◦ Endpoint definitions

◦ Analysis plan

◦ Methods for interpretation of study results

◦ Targeted labeling claim

Clinical practice and study setting◦ Inpatient vs. outpatient

◦ Geographic location

◦ Clinical practice variation

Not all patient reported, clinical-reported, observer-reported, or performance outcome assessments are appropriate Clinical Outcome Assessments for use in clinical trials to support approval and labeling◦ May be useful for other purposes:

◦ Diagnostic

◦ Prognostic

◦ Trial eligibility and trial enrichment

◦ Epidemiologic or population studies

◦ Clinical practice decision-making

◦ Measures used successfully for these other purposes will not necessarily be appropriate outcomes assessments (i.e., they may not be able to reliably detect treatment benefit in clinical trials or support labeling claims in a non-misleading way)

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Clinical Outcome Assessment Considerations

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1. ICH.Org

2. FDA, Office of New Drugs (OND), Center for Drug Evaluation and Research (CDER): FDA Approach to Outcome Measures

References