Cycle 1 2019: Treatment for Anxiety Disorders in Children, - PowerPoint PPT Presentation

Cycle 1 2019: Treatment for Anxiety Disorders in Children, Adolescents, and/or Young Adults Town Hall January 22, 2019

Agenda • Welcome and Introductions • PFA overview Submit questions via the questions box in • Patient and Stakeholder GoToWebinar. Engagement • Administrative Requirements • Merit Review • Resources • Questions?

Today’s Presenters Laura Esmail, PhD, MSc Lisa Stewart, MA Roycelynn Mentor-Marcel Geeta Bhat, MPH, PMP Mercedes Alexander Senior Engagement Program Officer Program Associate Senior Administrator PhD, MPH Officer Clinical Effectiveness and Clinical Effectiveness and Contract Management Merit Review Officer Public and Patient Decision Science Decision Science Program Support & Engagement Information Management

PCORI’s 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. PCORI is particularly interested in research conducted in real-world settings that will facilitate widespread dissemination and implementation of findings. 4

Funding Announcement: Treatment of Anxiety Disorders in Children, Adolescents, and/or Young Adults

PFA Overview: Treatment of Anxiety Disorders in Children, Adolescents and/or Young Adults Objective of this PFA: • Fund high-quality clinical studies that compare the effectiveness of two or evidence-based clinical strategies to treat anxiety disorders in children, adolescents, and/or young adults. Available Funds and Duration : ▪ A total of $20 million funds available for this initiative ▪ Up to $5 million in total direct costs per project ▪ Projects must be completed within 3.5 years

Treatment of Pediatric Anxiety Disorders: the need for more evidence • Patients, caregivers, researchers, and stakeholder organizations have indicated the need for CER that examines the treatment options for pediatric anxiety disorders • Evidence is significantly lacking for:​ – Head-to- head comparisons of individual medications​ – Comparisons of CBT versus medications​ – Comparisons of combination therapy (CBT + medication) versus monotherapy​ – Approaches to treatment sequencing and the discontinuation of treatment • Larger trials (>300 participants) with longer follow-up are needed to address these evidence gaps Wang Z, Whiteside S, Sim L, et al. Anxiety in Children. Comparative Effectiveness Review No. 192. (Prepared by the Mayo Clinic Evidence-based Practice Center under Contract No. 290-2015-00013-I.) AHRQ Publication No. 17-EHC023- EF. August 2017.

Pediatric Anxiety Disorders: Topic history • To address these evidence gaps, PCORI issued a series of funding announcements • PCORI solicited and funded a Pragmatic Clinical Studies (PCS) Special Area of Emphasis topic for Cycle 2 2017 • Studies that compare the effectiveness of one or more digital applications of CBT to an appropriate active control (e.g., face-to-face CBT) for the treatment of mild-to-moderate anxiety in children, adolescents, and/or young adults (through age 25) • For PCS Cycle 3 2017 and PCS Cycle 1 2018, PCORI issued a priority topic: • Studies that compare the effectiveness of two or more evidence-based approaches for the treatment of anxiety in children, adolescents, and young adults (through age 25) • Studies which examine comparisons of different approaches to treatment initiation, sequencing, monitoring, maintenance, and/or relapse prevention following an initial effective course of treatment • For Cycle 1 2018, PCORI issued a targeted funding announcement: • Studies of head-to-head comparisons of pharmacological therapies, in conjunction with evidence-based psychological therapies for children, adolescents, and/or young adults with moderate to severe anxiety 8

PFA: Treatment for Anxiety Disorders in Children, Adolescents, and/or Young Adults The goal: to generate needed scientific evidence to help patients, families, and clinicians to make decisions about clinical strategies for the treatment of children, adolescents and/or young adults with anxiety disorders. 9

Design Considerations : Population • Children, adolescents, and/or young adults with a confirmed clinical diagnosis of a primary anxiety disorder between 7 and 25 years of age • Clearly define the specific age range to be studied, and provide a scientific rationale for the proposed study population • Clinical diagnoses including any co-morbidities must be specified • Clearly define the patient population – Type(s) of anxiety disorder(s), anxiety severity, exposure to previous treatment(s)/treatment failure, recurrent or relapsed illness, patient co-morbidities, and/or subpopulations – Application must explain how the study will ensure that recruited participants have a confirmed clinical diagnosis of a primary anxiety disorder • Robust sample sizes of at least 300 participants are required – Letters of intent that propose sample sizes of fewer than 300 participants will be considered nonresponsive 10

Design Considerations: Interventions • Clinical strategies may include pharmacological interventions, psychological interventions, or a combination of both. – Each proposed comparator must be clearly defined, evidence-based, and widely available – Comparators should be appropriate for the age range and disorder severity of the study population • Comparisons should reflect meaningful clinical decisional dilemmas where uncertainty exists in the choice between two or more treatments for a specific patient population – Is this comparison supported by the evidence base and evidence gaps identified? – Is the comparison feasible in the context of current clinical practice patterns and availability of treatments in the study setting? • Psychological services (if proposed) should be characterized according to the PCORI Methodology Standards for Studies of Complex Interventions. 11

Design Considerations: Outcomes • Patient- and family-centered outcomes that are well validated, responsive to change where baseline measures are employed, and developmentally appropriate for the proposed study population • Outcomes should at least include the following domains: – Function (e.g., school attendance, avoidance behavior) – Symptoms (child-, parent-, and/or clinician-reported, as scientifically justified) – Acceptability of treatment (e.g., family burden, adherence, dropout from therapy) – Adverse effects • Consider including an outcome (primary or secondary) that permits comparison of results across similar studies 12

Design Considerations: Timing • Studies must include at least nine months of follow-up from baseline, with one year of follow-up preferred • Applicants should clearly specify the duration and dose of each of the active interventions as well as the duration and timing of any maintenance or booster sessions 13

Design Considerations: Setting and Study Design • Setting – Studies may take place well-defined, primary, specialty, and/or integrated clinical care settings – Models that employ care coordination and integration across settings are encouraged • Study designs – Randomized controlled trials – Prospective, observational studies with large sample sizes 14

Safety Considerations • Applicants must include an adequate and appropriate human subjects protection plan – For example: inclusion of a data safety monitoring board, a risk monitoring plan, and discussion of potential risk and how it will be monitored in the consent process and during study conduct • Applicants who propose off-label use of medications should anticipate the potential need to file an Investigational New Drug (IND) application for Food and Drug Administration (FDA) approval

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 54 standards can be grouped into 2 broad categories and 13 topic areas. Cross-Cutting Standards Design-Specific Standards • • Formulating Research Questions Data Registries • • Patient Centeredness Data Networks • • Data Integrity & Rigorous Analyses Causal Inference Methods* • • Preventing/Handling Missing Data Adaptive & Bayesian Trial Designs • • Heterogeneity of Treatment Effects Studies of Medical Tests • Systematic Reviews • Research Designs Using Clusters • Studies of Complex Interventions *The first standard for Causal Inference Methods (CI-1) is considered cross-cutting and applicable to all PCOR/CER studies. 16

Patient and Stakeholder Engagement

Patients and Other Stakeholders Patient/ Consumer Caregiver/ Family Purchaser Member of Patient Payer Clinician PCORI Community Patient/ Caregiver Industry Advocacy Org Hospital/ Policy Health Maker System Training Institution

Patient-Centeredness vs. Patient Engagement • Patient-Centeredness – Does the LOI mention outcomes (both benefits and harms) important to patients? – Are the interventions being proposed for comparison available to patients now? • Patient and Stakeholder engagement – Does the LOI mention intent to build an interdisciplinary study team that includes appropriate patient and stakeholder representation in consultation with PCORI?