A systematic review of data from observational studies for the development of a Core Outcome Set to support future real-world evidence studies in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), a term encompassing ulcerative colitis (UC) and Crohn’s disease (CD) and IBD unspecified (IBD-U), is a complex, chronic, relapsing and remitting condition. Although associated with low mortality there is significant morbidity, manifesting as debilitating physical and psychosocial symptoms, resulting in an overall increasing global healthcare burden. Randomised controlled trials in IBD are the gold standard evidence for regulatory approval of new treatments or new indications. Whilst such experimental studies are important for therapeutic benefits, they may be an unsuitable study design to answer other types of research questions particularly those reflective of everyday clinical scenarios and real-world patient populations. Observational studies collecting pre-specified data or using secondary data collected for other purposes within defined data sources address questions of aetiology, prognosis, diagnosis, prevention and harm encompassed in epidemiology. The source of secondary data for observational studies may be collected during delivery of healthcare and referred to real world data (RWD) or routinely collected data. Such data is often derived from previous population-based or cohort studies, administrative datasets, disease databases, and disease registries. There is considerable heterogeneity in collected baseline variables and reported outcomes in real world clinical settings when evaluating IBD and its therapies, which makes meaningful comparisons of such results challenging. The development of a core outcome set (COS) for real world data in IBD could overcome these universal barriers, but has not yet been identified.

Aim

This systematic review will aim to categorise and describe all baseline characteristics, outcomes, measurement instruments used in real-world data studies in IBD. It represents the first step in the process of developing a COS in clinical practice that can be used for future RWE studies in IBD. More specifically, it will generate evidence for developing a COS for RWD collection in clinical practice with the purpose of facilitating future comparative effectiveness studies across Europe.

Contributors

JMG van Oostrom, Charlotte Wong

Supervisors: Dr. K. Gecse and N. Arebi

Further Study Information

Current Stage: Ongoing
Date: January 2020 - September 2021
Funding source(s): European Crohn's and Colitis Organization


Health Area

Disease Category: Gastroenterology

Disease Name: Crohn's disease, Inflammatory bowel disease (IBD), Ulcerative colitis

Target Population

Age Range: 18 - 120

Sex: Either

Nature of Intervention: Any

Stakeholders Involved

- Clinical experts
- Patient/ support group representatives
- Researchers

Study Type

- COS for practice

Method(s)

- Consensus conference
- Interview
- Literature review
- Systematic review

The protocol for the systematic review will follow the PEO (population, exposure/intervention and outcome) framework which is applicable to exposure to drugs/surgery/endoscopy and exposure to observation without intervention in routine clinical care. The purpose is to provide evidence to justify minimum COS that should be collected in clinical practice for CD and UC to facilitate future collaborative studies.

Research questions
1. What disease and treatment related outcomes are reported in observational IBD studies?
2. Which outcome measurement instruments are being used for these outcomes?
3. What types of data are collected to support the relevance of the outcomes?

The systematic review will be registered on PROSPERO and with the COMET initiative. We will adopt the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analyses) guidelines for carrying out the study.

Literature search
The literature search will be conducted for IBD, CD and UC. Relevant electronic databases will be searched to identify all observational trials involving patients with IBD. The following databases will be searched:
1. MEDLINE (OVID)
2. EMBASE (OVID)
3. CINAHL

Screening of studies
References from database searches will be exported to the Covidence Systematic Review Software (Vertias Health Innovation, Melbourne, Australia; available at www.covidence.org) for screening. Two independent reviewers will independently screen each study for eligibility criteria detailed in section 4.3 (CW and JvO). The titles and abstracts of the studies will be screened initially before full-text review. Any discrepancies on the eligibility of studies to be included will be resolved through discussion or resolved through a third and fourth reviewer (NA and KG). Duplicates and studies with exclusion criteria will be removed. All articles will be managed through an online reference manager (EndNote) for ease and to reduce duplication. A PRISMA flow chart will be constructed.

Data extraction
Data extraction will be performed independently by two reviewers (CW and JvO) using the same data extraction questions. The details of the extracted articles will be entered into Microsoft Excel using a pre-designed form, piloted before full data extraction with a sample of included studies.

We will use the STROBE and RECORD checklists to define important and relevant data for extraction with regards to study design, population selection, data sources and outcome events.

The primary reviewer will extract the following baseline data for CD and UC studies: author, date of publication, journal name, type of study, focus of study (disease based or therapy based), countries in which the study was conducted, sample size, participant characteristics (age, gender, smoking), disease phenotype (Montreal classification), extra-intestinal manifestations, type of interventions (no intervention, medication, surgery, endoscopy), length of follow-up, disease activity as inflammatory biochemical markers (leucocyte count, platelet counts, haemoglobin, CRP, albumin and faecal calprotectin), disease outcomes as: clinical scoring indices (Harvey Bradshaw Index, Crohn’s Disease Activity Index, Mayo score , SCCAI), endoscopic scoring indices (CDEIS, SES-CD, Rutgeert’s Score, UCEIS, Mayo), histological and radiologic tests (type and any relevant scores or descriptors), types of quality of life scores and disease-related complications (such as haemorrhage, cancers, primary sclerosing cholangitis, intra-abdominal sepsis/collection, strictures, bowel obstruction, perforation, fistulas, mortality, thrombotic events) and therapy-related complications (such as skin reactions, allergies/anaphylaxis, renal or hepatic impairment, neurological impairment, cardiovascular compromise, infections, thrombosis, malignancy and death).

Categorisation of outcomes
The Outcome Measures in Rheumatology (OMERACT) consensus initiative in 1992 was successful in developing COS for many rheumatological conditions. It published a conceptual framework and recommended pathway for developing COS that may be used as a template for other healthcare areas [13]. This is supported by the international COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN)/Core Outcome Measures in Effectiveness Trials (COMET) guidelines. By using their OMERACT Filter 2.0, clinical outcomes are defined as any outcome that would fall under the four core areas of life impact, resource use and pathophysiological manifestations for the specific condition (IBD in this instance) including adverse events and death.

Data analysis
Two reviewers (CS and JvO) will categorise outcomes into domains, to be reviewed and modified by the steering committee. The frequency of each outcome measure reported across studies will be calculated. Quality assessment tools are not used in COS development as most of these aim to assess the risk of bias on overall results rather than what outcomes were chosen.

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