The Comparative Health Outcomes in Immune- Mediated Diseases - - PowerPoint PPT Presentation

The Comparative Health Outcomes in Immune- Mediated Diseases Collaborative (CHOICE) Study

Jeffrey Curtis, MD, MS, MPH

Professor of Medicine @RADoctor

Shilpa Venkatachalam, PhD

Associate Director, Patient- Centered Research GHLF

Jeffrey Cur Curtis, M , MD, , MS, M , MPH: Consulting fees and contracted research with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lily, Janssen, Maraid, Phizer, Regeneron, Roche, and UCB. Shilpa a Venkatac achal alam am, P PhD: I can confirm that I do not receive any direct funds from industry related to RA, nor do I in any capacity bear relationship with industry, including pharmaceutical companies related to RA that may pose as a conflict of interest in my capacity researcher for the CHOICE study. I am currently employed by the Global Healthy Living Foundation as the Associate Director, Patient Centered Research. GHLF receives grants and sponsorships from pharmaceutical manufacturers as well as other private foundations. A full list of GHLF funders is publicly available here: https://www.ghlf.org/our-partners/ None of these partners, however, have the potential to bias or appear to bias my involvement in this project. Any possible conflict of interest that might arise will be reported promptly by GHLF.

Resea earcher P Per erspecti ective: C CHOICE S Study

Backgroun und: d: Need to make challenging decisions amongst a variety of treatment options for autoimmune and inflammatory conditions given widely variable safety profiles; limited data on medication effectiveness from patients’ perspective Aim 1 m 1: Safety of immunomodulatory medications (e.g. biologics), researcher perspective Aim 2 m 2: Comparative effectiveness of immunomodulatory medications, patient perspective Data i infrastructure

• EHR data from 3 CDRNs
• Patient data from 5 PPRNs
• Health plan claims

Recruitment ( (Aim 2 Sub ub-AIM) M)

• CDRNs recruit patients to PPRNs
• PPRNs recruit patients to Study

Example le o

• f v

f varia riabili lity in CDM d data provided

• Low percent = GOOD
• Includes zero refills for

autoimmune prescription refills

Variability i in Sidecar Data p provided

AIM 1 1 Safety R ty Results ts f from

• m C

CDRN S Sites

De Def 0) 0) no requirement for any prior data; De Def 1) 1) >6 months (m) from first medical inpatient or outpatient medical encounter

• f any type; De

Def 2) 2) >6m from first prescription [Rx] for any medication; De Def 3) 3) >6m from first medical encounter for disease indication (e.g. RA, vasculitis); De Def 4) 4) >6 m from first prescription for any disease-specific rheumatologic therapy

AIM 1 1 Data that c could be l be link nked t to CMS D Data

Total patient data received from CDRNs N = 183,372 Patients with some autoimmune disease N= 170,032 Patients with RA, PsA, PSO, IBD, AS, Vasculitis or JIA diagnosis code N = 173,545 Patients with any medication information (including parenteral medications) N = 140,838 Patients with any RA, PsA, PSO, IBD, AS, Vasculitis or JIA medications N = 63,885 Patients classified as having RA, PsA, PSO, IBD, AS, Vasculitis or JIA after using a Rx/Px for these diseases, but no additional drugs for these diseases afterward N = 31,878 After excluding for HIV/Cancer/SLE/Organ Transplant/autoimmune diagnosis before 6 months N = 37,453 After excluding for vasculitis (except for the vasculitis cohort) N = 37,393 Patients linked to CMS data N = 1,956

ArthritisPower patients (AIM 2) who could be linked to CMS data

5,637

Patients with Medicare (Medicare advantage)

5,559

Patients with date of birth (DOB)

5,545

Patients with sex

5,544

Patients with zip code

2,352

Patients uniquely linked based on DOB, sex and zip code

AIM 2 Patient Reported Outcomes (PROs) Example from PARTNERS data analyses

Aimed to compare baseline PROs to 6 months after newly starting a medication for treatment of JIA Inclusion criteria:

• PRO measured with 30 days prior or 7 days after newly starting

medication (methotrexate or biologic)

• Subsequent PRO measured between 3 and 8 months after newly

starting medication Outcome:

• PROMIS measures of Pain interference, Physical function, Fatigue
• Patient/Parent Global Assessment of Disease Activity
• If newly started medication was discontinued prior to 6 month PRO

measurement, then most recent score (including baseline score) was assessed.

Impor

• rtant D

t Differ eren ences ces in B Baseline e Characteristi tics cs

MTX monotherapy TNFi monotherapy MTX+TNFi combination % RF+ Polyarthritis 12% 10% 25% % Spondyloarthritis 18% 50% 23% Mean disease duration (days) 222 580 110 % High disease activity 78% 79% 87%

Initi tial analyses show t that h t high gh d disea ease a acti tivity ty i is strongly a associated wi with s subsequent t improvement i t in PRO ROs.

Changes es i in PROMIS P Pain I Inter erfer erence ce

MTX MONOTHERAPY TNFI MONOTHERAPY MTX+TNFI COMBINATION

Number of patients 176 42 40 Baseline Score Mean/Median 55.41 / 55.70 57.05 / 58.00 57.95 / 59.00 Mean Delta

• 4.11
• 2.75
• 7.51

Median Delta

• 2.70
• 0.50
• 5.75

Chan anges i s in n PROMIS P Physi sical F Function

MTX monotherapy TNFi monotherapy MTX+TNFi combination Number of patients 193 31 39 Baseline Score Mean/Median 39.21 / 37.90 37.78 / 36.90 35.27 / 34.20 Mean Delta +7.37 +6.69 +10.20 Median Delta +6.00 +4.90 +6.90

PARTNERS AIM 2 Summary to Date

• Clinically relevant improvements in PROs were
• bserved following initiation of new medications
• There appear to be differences in improvement

across different medication choices, but important baseline differences in patients’ characteristics (especially disease activity and possibly disease phenotype) necessitate adjusted analyses

Ad Admini nistratively

• SMART IRB functionality was limited
• Variability in SMART IRB capacity among CDRN/PPRN sites
• Local IRB approvals still required by sites even when using

SMART IRB

• Template DUA not accepted “as is” for all sites; changes

requested AFTER execution

• Uncertainties about DUA permissions to share LDS (vs. de-

identified)

• Contractual processes and governance structures varied by

CDRN and by individual site

• Contractual/IRB dependencies – i.e. Human subjects protocol

cannot be submitted to IRB without contract number, but contract cannot be routed without IRB approval; DUA requires IRB approval

AIM 1

• Should involve ALL possible stakeholders early in the process (i.e. statisticians/programmers

were not oriented to the protocol when it was time to extract the data)

• Variability in CDRN data that was available (both CMD and sidecar)
• CDRNs had varying levels of standardization to the CDM, with some having no

centralization.

• Missing 45-100 % of refill data on autoimmune diseases.
• Mother-baby linkage data was not available at four of the five data marts because (1)

IRB nightmare to get baby IDs, (2) there was a limited number of female RA patients of child-bearing age who had babies at the data mart and (3) it was just not available.

• PCORnet CDM was inadequate for representation of the data
• QA/QC was difficult between CDM versions (data was extracted by the data marts, but

while waiting for DUA execution, the data marts updated their CDM versions)

• Necessary to have a physician champion at each data mart

AIM 2

• No harmonization in PRO data collection, frequency and method of collection by PPRNs
• Variability in flexibility of PPRNs to modify existing PRO collection versus using concurrently

collected data for other studies

• Establishing the baseline anchor not possible in all PPRNs - Added two additional outcomes

to compensate

• Standardized CDRN to PPRN recruitment letters proved an impossibility
• Variability in CDRN recruitment capacity
• One data mart’s patient portal team requested changes to the vetted and IRB approved

recruitment letters requiring a 4-month delay

• One data mart waited 3.5 months for IRB approval related to messaging patients

through the patient portal

• One data mart lacked the capacity and had to build the infrastructure
• One data mart was unable to engage in active messaging (could use passive messaging)
• PPRNs were split over whether to invite members to JOIN the CHOICE study vs. ask them to

provide more (or regular) data without actually joining the study

Stakeh ehol

• lder

er Perspect ective

What do we mean by stakeholder (patient) perspective?

Patients are the only o

• nes who can tell researchers how well or not well a treatment

works for them, how to best contact them, and how often they want to provide data.

Why include patients?

• Patient Reported Outcomes (PROs) can only come

from patients.

• This data, from thousands of patients, is then turned

into information that physicians and other patients use to make decisions about treatments.

• But, how can researchers feasibly connect with and

engage thousands of patients

Patien ent P Power ered ed R Resea esearch h Net etworks ( s (PPRNs)

User opens app and is prompted through a ‘wizard-like’ process to participate in a study via a walk-through tailored to their cohort providing an enhanced user experience.

How we were patient stakeho holders engaged?

Regular (e.g. monthly) patient governor meetings that included updates and feedback on the CHOICE Study Guidance on which PROs were most important to patients (fatigue, pain interference, physician function – not IBD, social participation – DSA) Recruitment materials: creating and vetting the recruitment letters and messaging Frequency of data collection: once to twice a month for 3- 6 months Reducing attrition - compensation (?) and, if yes, what type and how much Sustaining engagement for continued participation in longitudinal studies

Autoimmune and Systemic Inflammatory Syndromes Collaborative Research Group (ASIS CRG) PPRN Representation

Autoimmune ArthritisPower (ARthritis patient Partnership with comparative Effectiveness Researchers) – Adult rheumatology CCFA Partners (Crohn’s & colitis foundation of America) – Adult IBD PARTNERS (Patients, Advocates and Rheumatology Teams Network for Research and Service) – Childhood rheumatology ICN (ImproveCareNow: A Learning Health System for Children with Crohn’s Disease and Ulcerative Colitis) – Child IBD V-PPRN (Vasculitis Patient Powered Research Network) MS –PPRN (Multiple Sclerosis Patient-Powered Research Network)

Engaging with patient participants

• Education in-app and via CreakyJoints

website and social media platforms

• Engagement webinars on current research

studies and other topics of interest to patients – CHOICE Webinar

• Frequent email contact
• Monthly reminders to complete PROs

and medication data

• Quarterly newsletter
• Announcements of special events and

milestones

• Annual summary of participation
• Webinar alerts

Learn More

• www.pcori.org
• info@pcori.org
• #PCORI2019
• Arthritispower.org

Questions?

Thank You!

Jeffrey Curtis, MD, MS, MPH

Professor of Medicine @RADoctor

Shilpa Venkatachalam, PhD

Associate Director, Patient-Centered Research GHLF