Post-Market Applications of Benefit- Risk Assessment!

Transcription

1 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. " 1

2 speakers! Joseph Ross MD, MHS Joseph Selby MD, MPH Sean Tunis MD, MSc Lona J. Vincent MPH Assistant Professor of Medicine and of Public Policy, Yale University School of Medicine Executive Director, Patient-Centered Outcomes Research Institute Founder & CEO, Center for Medical Technology & Policy Senior Associate Director, Michael J. Fox Foundation for Parkinson s Research MODERATOR

3 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

4 Benefit vs. Risk Certainty vs. Uncertainty (Need to Communicate with Pa:ents)

5 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

6 Pa:ent Values & Preferences Research Evidence Clinical Context

7 Models of Treatment Decision Making Direc:on and amount of informa:on flow about op:ons Direc:on of informa:on flow about values and preferences Parental Clinician- as- perfect agent Shared decision- making Informed Clinician >> Pa:ent Clinician >>>> Pa:ent Clinician <<>> Pa:ent Clinician >>>> Pa:ent 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:

8 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

9 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

10 Structuring Clinical Encounter for SDM HEAD BODY TAIL SUPPORT BEFORE VISIT SUPPORT DURING VISIT SUPPORT AFTER VISIT Clinicians Acquire best available evidence on risks and benefits of options Gather information on patient s preferences Patients Gather pertinent background information about condition Other Opportunities 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

11 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?

12 Pa:ent- Important Outcomes in Registered Diabetes RCTs Primary Endpoint Pa$ent- Centered outcome (e.g., death, morbidity, quality of life) Surrogate markers of disease (e.g., glycosylated hemoglobin, cholesterol) Physiological measurements (e.g., insulin levels) Pa:ent- Centered Outcomes as Primary or Secondary Endpoint 436 Phase II- IV RCTs registered on ClinicalTrials.gov, % 61% 16% 46% Source: Gandhi et. al., JAMA 2008;299:

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14 Source: hxp://shareddecisions.mayoclinic.org/.

15 Source: hxp://shareddecisions.mayoclinic.org/.

16 Source: hxp://shareddecisions.mayoclinic.org/.

17 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? Source: Shepherd et. al., Pat Educ Couns 2011;84: Need research to answer (and confidence to convey uncertainty)

18 PCORI s Approach to Research and Communication on Potential Benefits and Harms Of Treatments Joe Selby MD Executive Director September 23, 2014 George Washington University 18

19 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.

20 We Have a Broad and Complex Mandate The purpose of the Institute is to assist patients, clinicians, purchasers, and policymakers 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 from Patient Protection and Affordable Care Act

21 Our Mission 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.

22 Engagement is PCORI s Key To Relevant, Useful Research Topic Selection and Research Prioritization Proposal Review; Design and Conduct of Research ENGAGEMENT Evaluation Dissemination and Implementation of Results

23 Who Are PCORI s Stakeholders? Purchaser Patient/ Consumer Caregiver/ Family Member of Patient Payer Clinician PCORI Community Industry Patient/ Caregiver Advocacy Org Policy Maker Training Institution Hospital/ Health System

24 What is Patient-Centered CER? " 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

25 Pre- and Post-Approval Assessments are Linked Approval Drug Development Post-Marketing Clinical Benefit (efficacy) Common Side Effects Safety Comparative Effectiveness Less Frequent Side Effects Safety 25

26 Pre- and Post-Approval Assessments are Linked Earlier Approval Drug Development Post-Marketing Clinical Benefit (efficacy) Common Side Effects Safety Comparative Effectiveness Less Frequent Side Effects Safety 26

27 Pre- and Post-Approval Assessments are Linked Approval Drug Development Post-Marketing Clinical Benefit (efficacy) Common Side Effects Safety Comparative Effectiveness Less Frequent Side Effects Safety Predictors of Effectiveness and Safety (heterogeneity) 27

28 28 PCORI s Research Agenda 2011 Pilots Methods for engaging patients and stakeholders in CER Any clinical area Up to $500,000, two years 2012 Broad CER Any clinical area in which practice could be changed Up to $1.5 million, three years 2013 Targeted CER Single clinical area Larger, variable funding amounts, 3-5 years 2014 Pragmatic CER; intense engagement required List of high priority topics, narrow research questions Up to $10 million, five years

29 Topics Invited (n=36) for First Round of Pragmatic Clinical Studies TOPIC PCORI PRIORITY IOM CER 100 AHRQ FRN CVD preven$ve care (5) Q1 Diabetes preven$on Dental caries preven$on Q1 Q1 Smoking cessa$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 Use of Colony S$mula$ng Factor in CA Q4 Q3 New Hepa$$s C therapies Q4 Treatment of Migraine Headache 29 Q4

30 Topics Invited (n=36) for First Round of Pragmatic Clinical Studies (continued) 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 30

31 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 decisionmaking 31

32 Funded PCORI Research on Development of Patient-Centered Decision Aid Tools 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) 32

33 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 40

34 Find Us Online 45

35 WHAT KIND OF EVIDENCE ARE PAYERS LOOKING FOR? September 23, 2014 Sean R. Tunis, MD, MSc. President and CEO

36 BMJ Clinical Evidence 2013 LOTS OF UNCERTAINTY

37 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 37 37

38 WHAT IS MISSING DRUG EXAMPLE 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 38 38

39 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

40 EVIDENCE FOR REGULATORS VS PAYERS Characteristic Research question: Patient population: Intervention: Comparator(s): Compliance: Outcomes: Time frame: 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 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 Setting of care: Controlled; e.g., center of excellence Community practice; often diverse 40 40

41 THE RCT READY TO RETIRE?? 1970s

42 RISING STARS OF CLINICAL EFFECTIVENESS Modeling Big Data Advanced Obs 42

43 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 43

44 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 44

45 CONTACT INFO x120 (D) (M) 45

46 EXTRA SLIDES

47 Elements in a US payer assessment of value Addi$onal Benefits for Pa$ent, Family, Delivery System, Society Contextual Considera$ons: illness and therapy Compara$ve Cost Compara$ve Clinical Effec$veness Value Contextual Considera$ons: cost, delivery system and market Copyright ICER 2014

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49 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 49

50 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 50

51 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

52 GPC RECOMMENDATIONS - MDX TESTS IN ONCOLOGY Measuring outcomes for CU studies Clinical Utility 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 52

53 GPC RECOMMENDATIONS: OBSERVATIONAL STUDIES Clinical Utility 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 53

54 Questions?!