the comparative health outcomes in immune- mediated ... · shilpa venkatachalam, phd: i can confirm...
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The Comparative Health Outcomes in Immune-Mediated Diseases Collaborative (CHOICE) Study
Jeffrey Curtis, MD, MS, MPHProfessor of Medicine
@RADoctor
Shilpa Venkatachalam, PhDAssociate Director, Patient- Centered Research GHLF
Jeffrey Curtis, MD, MS, MPH: Consulting fees and contracted research with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lily, Janssen, Maraid, Phizer, Regeneron, Roche, and UCB.
Shilpa Venkatachalam, 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.
Researcher Perspective: CHOICE Study
Background: 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: Safety of immunomodulatory medications (e.g. biologics), researcher perspective
Aim 2: Comparative effectiveness of immunomodulatory medications, patient perspective
Data infrastructure EHR data from 3 CDRNs Patient data from 5 PPRNs Health plan claims
Recruitment (Aim 2 Sub-AIM) CDRNs recruit patients to PPRNs PPRNs recruit patients to Study
Example of variability in CDM data provided
• Low percent = GOOD
• Includes zero refills for autoimmune prescription refills
Variability in Sidecar Data provided
AIM 1 Safety Results from CDRN Sites
Def 0) no requirement for any prior data; Def 1) >6 months (m) from first medical inpatient or outpatient medical encounter of any type; Def 2) >6m from first prescription [Rx] for any medication; Def 3) >6m from first medical encounter for disease indication (e.g. RA, vasculitis); Def 4) >6 m from first prescription for any disease-specific rheumatologic therapy
AIM 1 Data that could
be linked to CMS Data
Total patient data received from CDRNsN = 183,372
Patients with some autoimmune diseaseN= 170,032
Patients with RA, PsA, PSO, IBD, AS, Vasculitis or JIA diagnosis codeN = 173,545
Patients with any medication information (including parenteral medications) N = 140,838
Patients with any RA, PsA, PSO, IBD, AS, Vasculitis or JIA medicationsN = 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 monthsN = 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.
Important Differences in Baseline Characteristics
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%
Initial analyses show that high disease activity is strongly associated with subsequent improvement in PROs.
Changes in PROMIS Pain Interference
MTX MONOTHERAPY
TNFIMONOTHERAPY
MTX+TNFICOMBINATION
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
Changes in PROMIS Physical 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 observed 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
Administratively
• 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
Stakeholder Perspective
What do we mean by stakeholder (patient) perspective? Patients are the only ones 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
Patient Powered Research Networks (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 were patient stakeholders 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 CreakyJointswebsite 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
Questions?
Thank You!Jeffrey Curtis, MD, MS, MPHProfessor of Medicine
@RADoctor
Shilpa Venkatachalam, PhDAssociate Director, Patient-Centered Research GHLF