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Post-Market Applications of Benefit-
Risk Assessment !Objective: Describe how information about benefits and
risks is used to evaluate safety, effectiveness, and value by patients, prescribers, and payers. "
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speakers!
Joseph Selby MD, MPH
Executive Director, Patient-Centered
Outcomes Research Institute
Joseph Ross MD, MHS
Assistant Professor of Medicine and of Public Policy, Yale University
School of Medicine
Sean Tunis MD, MSc
Founder & CEO,
Center for Medical Technology & Policy
Lona J. Vincent MPH
Senior Associate
Director, Michael J. Fox Foundation for
Parkinson’s Research
MODERATOR
Using Shared-‐Decision Making to Integrate Benefit-‐Risk with Pa:ents
FasterCures Benefit-‐Risk Boot Camp September 23, 2014
Joseph S. Ross, MD, MHS Sec$on of General Internal Medicine, School of Medicine
Center for Outcomes Research and Evalua$on, Yale-‐New Haven Hospital
Benefit vs. Risk Certainty vs. Uncertainty
(Need to Communicate with Pa:ents)
Uncertainty Tolerance Influenced By:
• Known (an:cipated) benefits and risk of treatment – interpreta:on of research evidence
• Seriousness of the disease • Morbidity and mortality • Func:onal impact
• Availability of alterna:ve txs • Personal values and beliefs • Past experience • Physicians’ recommenda:ons
Pa:ent Values &
Preferences
Clinical Context
Research Evidence
Models of Treatment Decision Making
Parental Clinician-‐as-‐perfect agent
Shared decision-‐making Informed
Direc:on and amount of informa:on flow about op:ons
Clinician >> Pa:ent Clinician >>>> Pa:ent Clinician <<>> Pa:ent Clinician >>>> Pa:ent
Direc:on of informa:on flow about values and preferences
Clinician >> Pa:ent Clinician <<<< Pa:ent Clinician <<>> Pa:ent Clinician << Pa:ent
Delibera:on Clinician Clinician Clinician, Pa:ent Pa:ent
Decider Clinician Clinician Clinician, Pa:ent Pa:ent
Consistent with EBM principles
Not when decision is not purely technical and there are op:ons
Yes Yes Yes
Source: Charles et. al., Soc Sci Med 1999;49:651-‐661.
Shared-‐Decision Making (with Empathy)
• Goal: Increase likelihood that pa:ents receive the care they need in a manner consistent with the best available research evidence and their values and preferences.
• Key Characteris:cs: 1. At least two par:cipants—physician and pa:ent 2. Both par:es share informa:on 3. Both par:es take steps to build a consensus
about the preferred treatment; and 4. Agreement is reached on treatment plan
When? Clear opportuni:es:
• When benefits and risks are closely balanced • When benefits clearly exceed risks only if pa:ents adhere to treatment
• When benefits and risks are not well known
Structuring Clinical Encounter for SDM
Clinicians
Patients
Other Opportunities
HEAD BODY TAIL
SUPPORT BEFORE VISIT
SUPPORT DURING VISIT
SUPPORT AFTER VISIT
• Acquire best available evidence on risks and benefits of options• Gather information on patient’s preferences
• Gather pertinent background information about condition
• Review available options – including the option to do nothing else• Explore likelihood of potential outcomes• Weigh risks and benefits of options• Make decision
Clinician & Patient• Review available options – including the option to do nothing else• Explore likelihood of potential outcomes• Deliberate across options, the risks and benefits• Make decision • Develop plan for moving forward – Set parameters to judge if course of action is working – Create action plan for adverse effects
Patients• Discuss and consult other trusted people and resources• Share plan with support network• Review decision making process and plan (Body) and contact provider if a new choice is needed• Execute plan (management and/or treatment) • Observe whether course of action is working• Refer to course of action when adverse effects take place
Research Evidence for SDM
• Will I live longer? • Will I feel beder tomorrow? In 1 year? • Will my symptoms be beder controlled? • Will I be able to move more easily? • Will I be able to beder take care of myself? • Will I not need to see the doctor as oeen or need to be hospitalized?
• Safety?
Pa:ent-‐Important Outcomes in Registered Diabetes RCTs
436 Phase II-‐IV RCTs registered on ClinicalTrials.gov, 2004-‐2007
Primary Endpoint
Pa$ent-‐Centered outcome (e.g., death, morbidity, quality of life)
18%
Surrogate markers of disease (e.g., glycosylated hemoglobin, cholesterol)
61%
Physiological measurements (e.g., insulin levels)
16%
Pa:ent-‐Centered Outcomes as Primary or Secondary Endpoint
46%
Source: Gandhi et. al., JAMA 2008;299:2543-‐2549.
Source: hXp://shareddecisions.mayoclinic.org/.
Source: hXp://shareddecisions.mayoclinic.org/.
Source: hXp://shareddecisions.mayoclinic.org/.
3 “benefit-‐risk” ques:ons every pa:ent should ask and every physician should be able to answer:
1. What are my op:ons? • What happens if I do nothing else?
2. What are the benefits and risks of each op:on?
3. How likely are these benefits and risks?
Need research to answer (and confidence to convey uncertainty)
Source: Shepherd et. al., Pat Educ Couns 2011;84:379-‐385.
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September 23, 2014 George Washington University
Joe Selby MD Executive Director
PCORI’s Approach to Research and Communication on Potential Benefits and Harms Of Treatments
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.
“The purpose of the Institute is to assist patients, clinicians, purchasers, and policy-makers in making informed health decisions by advancing the quality and relevance of evidence concerning the manner in which diseases, disorders, and other health conditions can effectively and appropriately be prevented, diagnosed, treated, monitored, and managed through research and evidence synthesis...and the dissemination of research findings with respect to the relative health outcomes, clinical effectiveness, and appropriateness of the medical treatments, services...”
We Have a Broad and Complex Mandate
-- from Patient Protection and Affordable Care Act
PCORI helps people make informed health care decisions, and improves health care delivery and outcomes, by producing and promoting high integrity, evidence-based information that comes from research guided by patients, caregivers and the broader health care community.
Our Mission
Evaluation
ENGAGEMENT
Engagement is PCORI’s Key To Relevant, Useful Research
Proposal Review; Design and Conduct of Research
Topic Selection and Research Prioritization
Dissemination and Implementation of Results
Who Are PCORI’s Stakeholders?
PCORI Community
Patient/ Consumer
Caregiver/Family
Member of Patient
Clinician
Patient/ Caregiver Advocacy
Org
Hospital/ Health System
Training Institution
Policy Maker
Industry
Payer
Purchaser
" Involves patients, consumers, other stakeholders in conducting and disseminating the research
" Compares two or more options for prevention, diagnosis, or treatment (can include “usual care”)
" Considers the range of clinical outcomes relevant to patients
" Conducted in real-world populations and real-world settings
" Attends to differences in effectiveness (both benefits and harms) and preferences across patient subgroups
" Often requires randomized trial design
What is Patient-Centered CER?
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Post-Marketing
Approval
Drug Development
Clinical Benefit (efficacy) Common Side Effects Safety
Comparative Effectiveness Less Frequent Side Effects Safety
Pre- and Post-Approval Assessments are Linked
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Post-Marketing
Earlier Approval
Drug Development
Clinical Benefit (efficacy) Common Side Effects Safety
Comparative Effectiveness Less Frequent Side Effects Safety
Pre- and Post-Approval Assessments are Linked
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Post-Marketing
Approval
Drug Development
Clinical Benefit (efficacy) Common Side Effects Safety
Comparative Effectiveness Less Frequent Side Effects Safety Predictors of Effectiveness and Safety (heterogeneity)
Pre- and Post-Approval Assessments are Linked
PCORI’s Research Agenda
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Pilots
• Methods for engaging patients and stakeholders in CER • Any clinical area • Up to $500,000, two years
Broad
• CER • Any clinical area in which practice could be changed • Up to $1.5 million, three years
Targeted
• CER • Single clinical area • Larger, variable funding amounts, 3-5 years
• CER; intense engagement required • List of high priority topics, narrow research questions • Up to $10 million, five years Pragmatic
2011 2012 2013 2014
Topics Invited (n=36) for First Round of Pragmatic Clinical Studies
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TOPIC PCORI PRIORITY IOM CER 100 AHRQ FRN
CVD preven$ve care (5) √ Q1
Diabetes preven$on Q1 Dental caries preven$on Q1
Smoking cessa$on (2) √ Q4
Risk-‐based breast cancer screening Q1 √
Surveillance of lung nodules (2) √
Breast ca/DCIS management (2) √
Treatment alterna$ves for Bipolar disorder √
Alterna$ves for DVT prophylaxis Q4
Use of Colony S$mula$ng Factor in CA Q3
New Hepa$$s C therapies Q4 √
Treatment of Migraine Headache √ Q4
Topics Invited (n=36) for First Round of Pragmatic Clinical Studies (continued)
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TOPIC PCORI PRIORITY IOM CER 100 AHRQ FRN
Sickle cell Disease therapy Q1 √ Proton beam therapy in cancer y Q1 Aor$c dissec$on repair (2) Management of low back pain (3) √ Q1 Improving medica$on adherence √ Q2 OA management, decision-‐making √ Q4 Stroke management Q3 Substance abuse treatment √ Chest pain ER management Cancer care med management √ Q2 Collabora$ve care in mental health √ Q4 Fragile X syndrome Gene$c tes$ng for CAD Q1
What’s the real problem? What do patients, clinicians need most?
§ Not enough information on the shelf § Large gaps in knowledge § Poor quality evidence § Need for more, better quality research
information
§ Plenty of information on the shelf § Not synthesized or presented in useful
ways at point of decision-making § Few effective tools for shared decision-
making
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Lung Cancer Screening Risk-Stratified Surveillance After Colorectal Cancer Resection Chest Pain in the Emergency Department Head CT Choice for Children with Head Trauma Mental Health Needs, Depression Care in Alaska Natives (2) Contraceptive Decision Making Treatment Choices for Minorities with Lupus Erythematosus Implantable Cardiac Defibrillators Nursing Home to Hospital Transfers Nephrotic Syndrome Symptomatic Diabetic Peripheral Neuropathy Ovarian Cancer Treatment Advanced Gastrointestinal Cancers Prostate Cancer Treatment and Care Choices (2) Palliative Chemotherapy (2)
H
Funded PCORI Research on Development of Patient-Centered Decision Aid Tools
How to Submit an Application
Visit pcori.org/apply " Key Dates " Funding Announcements " Application Guidelines and Templates " Guidance on the PCORI Methodology
Standards " Sample Engagement Plans " Frequently Asked Questions
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Find Us Online
www.pcori.org
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WHAT KIND OF EVIDENCE ARE PAYERS LOOKING FOR?
September 23, 2014 Sean R. Tunis, MD, MSc. President and CEO
LOTS OF UNCERTAINTY
BMJ Clinical Evidence 2013
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WHAT IS MISSING – DEVICE EXAMPLE
• FDA approves artificial discs for the neck • Medicare declines to cover them • Patients in trial all age 18 to 60 • Study showed non-inferiority to spinal fusion;
never shown to be better than no surgery • Need studies with older patients, and included
comparison to conservative care
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• Drugs for psoriasis approved based on extent and severity of total body surface area affected by plaques
• Patients state that face and joint involvement had biggest impact on QoL
• No validated “patient-centered” measures have been developed – Work is underway led by patient group
• FDA does not allow QoL on label for psoriasis drugs; EMA does allow them
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WHAT IS MISSING – DRUG EXAMPLE
WHAT PAYERS ARE LOOKING FOR
• Reflect broad range of patients (age, co-morbid) • Treatment provided in real world settings by clinicians
with a range of experience / skill • Reasonable (not extreme) efforts to ensure patient and/
or clinical adherence • Comparison with commonly used alternatives • Outcomes that are meaningful to patients • Reasonable length of follow-up
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EVIDENCE FOR REGULATORS VS PAYERS
Characteristic Research question: Patient population: Intervention: Comparator(s): Compliance: Outcomes: Time frame: Setting of care:
Regulatory Approval Can the drug work? Narrowly selected, similar baseline, limited comorbidities; some stratification Carefully managed/monitored dosing and side effects; expert practitioners Placebo or inferior treatment Strictly monitored, enforced Interm./surrogates; health outcomes if possible in short timeframe; little/no econ. Sufficient to detect statist. significant differences in interm./surrogate endpoints Controlled; e.g., center of excellence
Payment How well does the drug work in community/ general practice compared to standard of care? More diverse patients more likely to use drug in community practice; more subgroup analyses Less carefully managed; wider range of practitioner expertise/experience Standard of care/typical therapeutic alternative(s); may use indirect comparisons As in community practice; less actively enforced Health outcomes relevant to clinical decisions or policies; often economic Sufficient to detect statist. signif. and clinically important differences in health outcomes Community practice; often diverse
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THE RCT – READY TO RETIRE??
1970s 2013
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RISING STARS OF CLINICAL EFFECTIVENESS
Big Data
Modeling
Advanced Obs
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THE EVIDENCE PARADOX
• 18,000+ RCTs published each year • Tens of thousands of other clinical
studies • Systematic reviews and HTAs routinely
conclude that evidence is inadequate
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THE “CER HYPOTHESIS”
• Gaps in evidence will be reduced with greater engagement of patients, clinicians, payers – Identifying most important questions – Developing study protocols / methods – Peer review – Implementing studies
EXTRA SLIDES
Elements in a US payer assessment of value
Value Compara$ve Clinical
Effec$veness
Addi$onal Benefits for
Pa$ent, Family, Delivery System,
Society
Contextual Considera$ons:
illness and therapy
Compara$ve Cost
Contextual Considera$ons: cost, delivery system and market
Copyright ICER 2014
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EVIDENCE / INNOVATION CHALLENGE
• Development of more evidence of effectiveness, safety and value for payers, patients, clinicians, and policymakers
• While sustaining investment in life sciences and promoting innovation
• In an environment of strong downward pressure on spending
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OBTAINING PAYER/HTA PERSPECTIVE ON EVIDENCE
• Early Scientific Advice – Payers and HTA bodies – Parallel advice with regulators – Payer advisory boards and consultants
• Methodological Standards – General (PCORI, AHRQ, ISPOR) – Disease or technology-specific
• Green Park Collaborative • EUnetHTA
GREEN PARK COLLABORATIVE - USA
• A multi-stakeholder forum to clarify the evidence expectations of public and private payers ‒ Informed by input from patients, clinicians, ‒ Life sciences, regulators, research funders also
participate • Produce “effectiveness guidance documents” ‒ Condition and technology-specific study design
recommendations for researchers ‒ Analogous to regulatory guidance
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GPC RECOMMENDATIONS - MDX TESTS IN ONCOLOGY
Measuring outcomes for CU studies
CU studies of MDx tests should include outcome measures that assess patient benefits and harms
• Should include patient-reported outcome measures appropriate and validated for the clinical context
• May also include endpoints such as survival and downstream health care resource utilization
• Process measures are insufficient
• Studies designed to report intended care plans following an MDx test are insufficient to demonstrate CU
Clinical Utility
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GPC RECOMMENDATIONS: OBSERVATIONAL STUDIES
In some circumstances, longitudinal observational study designs are acceptable options for assessing CU
• Must have compelling rationale for not doing RCT
• Steps to minimize confounding must be documented
• Good research practices followed
• Retrospective studies not adequate for CU of MDx tests
• Secondary databases may be one source for data collection, but prospective data collection is needed
Clinical Utility
Questions?!