Second-line Pharmacological Treatments for Type 2 Diabetes Applicant Town Hall May 20, 2020
Agenda • About PCORI • Targeted Funding Announcement Overview • Patient and Stakeholder Engagement • Administrative Overview • Merit Review Process • Key Dates and Resources • Questions and Answers Submit questions via the Question box in GoToWebinar 2
Today’s Presenters Kim Bailey Allie Rabinowitz Christine Senior Program Broderick, MPH Senior Program Officer Engagement Associate Clinical Officer Clinical Effectiveness and Public and Patient Effectiveness and Decision Science Decision Science Engagemen t Mary Gardner Timna Wyckoff, Senior Contract PhD Administrator Merit Review Program Support Officer & Information Program Support Management & Information Management 3
About PCORI Allie Rabinowitz Senior Program Associate Clinical Effectiveness and Decision Science
Why PCORI? For all the advances it produces, research still has not answered many • questions patients face. People want to know which treatment is best for them. • Patients and their clinicians need information they can understand and use. • 5
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. 6
Our Work Answers Patients’ Questions Given my personal characteristics, conditions and preferences… 7
Focus on Comparative Clinical Effectiveness Research (CER) CER includes: Studies that compare health outcomes and the clinical effectiveness, risks, and benefits of • two or more approaches to healthcare • Clinical effectiveness research • Improving healthcare delivery CER • Communications and dissemination CER • CER to reduce/eliminate health and healthcare disparities All applicants should: • • Explain how the research is comparative • Name the comparators • State why the comparisons are important 8
Research We Do Not Fund PCORI does not fund research whose findings will include • development of clinical practice guidelines • coverage recommendations • payment or policy recommendations 9
Research We Do Not Fund PCORI does not fund studies of cost-effectiveness analysis (CEA). Examples of CEA • Research that conducts a formal CEA in the form of dollar-cost per quality-adjusted life-year (including non-adjusted life-years) to compare two or more alternatives • Research that directly compares the overall costs of care between two or more alternative approaches as the criterion for choosing the preferred alternative NOTE: PCORI does fund studies that explore the burden of costs on patients — for example, out-of-pocket costs. 10
2019 PCORI Methodology Standards Research funded by PCORI must adhere to the PCORI Methodology Standards, which represent minimal requirements for the design, conduct, analysis, and reporting of patient-centered outcomes research. The 65 standards can be grouped into 2 broad categories and 16 topic areas. Design-Specific Standards Cross-Cutting Standards Data Registries • Formulating Research Questions • Data Networks • Patient Centeredness • Causal Inference Methods* • Data Integrity & Rigorous Analyses • Adaptive & Bayesian Trial Designs • Preventing/Handling Missing Data • Studies of Medical Tests • Heterogeneity of Treatment Effects Systematic Reviews • • Research Designs Using Clusters • Studies of Complex Interventions • Qualitative Methods • Mixed Methods Research • Individual Participant-Level Data Meta-Analysis • *The first standard for Causal Inference Methods (CI-1) is (IPD-MA) considered cross-cutting and applicable to all PCOR/CER studies. 11
Funding Announcement Overview Kim Bailey Senior Program Officer Clinical Effectiveness and Decision Science 12
PFA Overview Objective of this PFA: • Fund high-quality studies using observational designs that compare the effectiveness of newer versus older second-line pharmacological agents in T2DM among individuals at moderate cardiovascular risk Available Funds: Up to $20 million • Total Direct Costs: Up to $4 million • Project Duration: Up to 3 years for all awards • 13
Second-line agents in T2DM The need for more evidence Beginning in 2008, the FDA mandated post-marketing studies for newly approved agents to • demonstrate cardiovascular safety 15 trials across 13 agents in 3 classes of drugs (DPP-4 inhibitors, SGLT2 inhibitors, and GLP- • 1 receptor agonists) are completed and have demonstrated CV safety Apparent cardiovascular benefit has been demonstrated for 6 agents in two classes: • • SGLT2 inhibitors: empagliflozin and canagliflozin • GLP-1 receptor agonists: liraglutide, semaglutide, albiglutide, dulaglutide Importantly, the CVOTs included patients with established CVD and those at very high CV • risk Question remains: Do these newer agents provide a CV benefit for lower risk individuals • compared with older agents? 14
Second-line agents in T2DM Why observational studies? Investment of time and resources to conduct randomized controlled trial • would be very large Lack of certainty regarding comparators to select/durability of information • for potential randomized trial Observational analyses may provide information about the relative risks and • benefits of these drugs and help to inform the design of a future trial 15
Design Considerations Overarching Methodological Guidance • Proposals should detail robust methods to emulate (to the greatest possible extent) a randomized controlled trial • See this white paper for an example • Approaches other than trial emulation may be deemed responsive if a clear rationale articulating how the proposed methods control for confounding is provided • Proposals should also clearly define and describe: • Approaches used to control for potential confounding; inclusive of a description of the approach used to validate measurements of treatment and potential confounders • Data sources and/or linkages from which data will be obtained • Approaches for handling missing data 16
Design Considerations Population • Must include adults with T2DM at moderate cardiovascular risk (2-3 annual risk of CV events); may be broader • Applicants should clearly specify the proposed patient population(s) and delineate key inclusion and exclusion criteria • Given PCORI’s interest in heterogeneity of treatment effects, studies that assess effects of agents in subpopulations are of interest • Specify subpopulation(s) to be analyzed 17
Design Considerations Interventions • Applications should propose comparisons of four second-line classes of T2DM drugs (SGLT2 inhibitors, GLP-receptor agonists, sulfonylureas, DPP-4 inhibitors) • Comparisons of individual agents within one or more classes are of interest • A strong justification is required if it is not possible to compare all four classes 18
Design Considerations Outcomes • Primary focus should be cardiovascular outcomes • Primary outcome(s) should include 3-point MACE (non-fatal MI, non-fatal stroke, and CV death) • Additional primary endpoints may be added • 4-point MACE inclusive of revascularization or hospitalization for heart failure may be of interest • Other outcomes of interest include individual components of MACE, all-cause mortality, glycemic control, renal function, medication side effects, weight gain or loss, and additional patient-centered outcomes (e.g., hypoglycemia) • Applicants should provide a clear rationale for the selection of proposed outcomes 19
Design Considerations Timing • Studies must be completed with 36 months • Analyses must include a minimum of 4 years of follow-up data • May be conducted solely with retrospective data • Some prospective data collection permissible if study can be completed within 36 months 20
Patient and Stakeholder Engagement Christine Broderick, MPH Engagement Officer Public and Patient Engagement
Patients and Other Stakeholders Patient/ Consumer Caregiver/ Family Purchaser Member of Patient Clinician Payer PCORI Community Patient/ Caregiver Industry Advocacy Org Hospital/ Policy Health Maker System Training Institution 22
Patient-Centeredness vs. Patient Engagement • Patient-Centeredness • Addresses comparisons that are of interest to patients, clinicians, and other stakeholders • Addresses outcomes (both benefits and harms) that are important to patients • Patient and Stakeholder Engagement • Demonstrates active engagement with patients and other stakeholders • Involves relevant organizations, community, patients, and caregivers through existing relationships or presents a well-thought out plan to establish these partnerships 23
Evidence of Appropriate Engagement of Relevant Patients and Other Stakeholders Applicants are expected to: • describe a conceptual approach to engagement tailored to the study and the target population • detail how patients, clinicians, and other relevant stakeholders will be actively engaged throughout the research process (e.g., identifying outcomes, monitoring the study, disseminating, and implementing) • establish appropriate organizational infrastructure and resources to engage patients and stakeholders throughout the conduct of the study 24
Recommend
More recommend
