Endoscopic scoring indices for evaluation of disease activity in Crohn’s disease

  • Protocol
  • Methodology

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

The primary objective is to systematically review the current literature describing the development and operating characteristics of endoscopic disease activity indices used to evaluate disease activity in Crohn's disease.

Background

Description of the problem or issue

Crohn’s disease (CD) is a chronic inflammatory disease of unknown aetiology that can affect any part of the gastrointestinal tract. Clinically the disease presents with diarrhea, abdominal pain, fatigue and weight loss and is characterized by chronicity and a relapsing-remitting course. Endoscopic findings include mucosal edema, erythema granularity, and friability and ulcers. Disease activity may be classified as mild, moderate, severe, or fulminant based on combined clinical and endoscopic assessments. Although CD may involve any part of the gastrointestinal tract, approximately 20% of patients have isolated colonic involvement, 30% have disease limited to the small bowel, and 50% of patients have involvement of both the ileum and the colon.

Several endoscopic and clinical indices have been developed to evaluate CD activity in clinical trials. It is now apparent that a poor correlation exits between symptoms as measured by an instrument such as the Crohn’s Disease Activity Index (CDAI) and endoscopic measures. Recently increased importance has been placed on the use of endoscopic instruments as outcome measures in clinical research since these are potentially more objective than symptom based indices. Therefore, the operating properties of these endoscopic indices must be clearly defined. In particular an endoscopic index must be valid – it must measure the outcome that it is intended to assess; responsive – it must detect a meaningful change in health status; and it must be reliable – meaning that consistent results are obtained in patients whose clinical status has remained stable (Kirshner 1985). Furthermore, an ideal instrument should be highly feasible to use in the setting of a clinical trial. Currently, the Crohn's Disease Endoscopic Index of Severity (CDEIS) (Mary 1989) and the Simple Endoscopic Score for Crohn's Disease (SES-CD) (Daperno 2004) are used to assess eligibility and response to therapy in clinical trials. However, it is notable that neither of these instruments have been fully validated.

The Crohn's Disease Endoscopic Index of Severity (CDEIS) assesses five segments of the intestine: rectum, sigmoid and left colon, traverse colon, right colon, and ileum (Mary 1989). The presence of deep and superficial ulceration, the percentage of ulcerated surface and the percentage of surface involved by CD are measured on a 10 centimetre visual analogue scale, for each colonic segment. Additionally, the presence of ulcerated stenosis and non-ulcerated stenoses are assessed. These items are weighted and summed to yield a total score that ranges from 0 to 44. Higher scores mean more severe disease. 

The Simple Endoscopic Score for Crohn's Disease (SES-CD) evaluates four endoscopic items (ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis). Each item is scored by segment on a scale from zero to three where higher scores indicate higher disease activity (Daperno 2004).

Why it is important to do this review

There are few data available on the operating properties of these two indices despite their widespread use as outcomes in clinical trials and systematic reviews. This review will evaluate the relative merits of the two indices and identify areas where further research is needed to develop an optimal evaluative instrument for use as an outcome in clinical trials and systematic reviews.

Objectives

The primary objective is to systematically review the current literature describing the development and operating characteristics of endoscopic disease activity indices used to evaluate disease activity in Crohn's disease.

Methods

Criteria for considering studies for this review

Types of studies

Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluate either or both of the SES-CD or CDEIS in patients with Crohn's disease will be considered for inclusion. Study subjects will include adult patients (> 16 years), diagnosed with Crohn's disease using conventional clinical, radiographic, and endoscopic criteria.

Types of data

Endoscopic scoring data obtained from eligible studies will be considered for inclusion.

Types of methods

The methods used to construct and validate the endoscopic indices (e.g. reliability, validity, responsiveness and feasibility) will be examined in detail and described for each eligible study. We will also report the number of endoscopists who scored the endoscopic indices in each study and whether these endoscopists were blinded or were aware of other raters scores.

Types of outcome measures

Reliability: Reliability in each study will be assessed by measuring reports of intra-rater and inter-rater reliability, test-retest reliability, or internal consistency. These will be assessed by determining the interclass correlation coefficient (ICC) for repeat assessments made by the same rater, and for assessments made by different raters.

Validity: Each study will be assessed to determine whether validity was measured, broadly defined as evidence that variations in Crohn's disease severity causally produce variations in the endoscopic indices measurement outcomes. Studies will be reviewed for whether content validity, criterion validity, or construct validity for endoscopic index scores in specific clinical situations have been reported.

Studies will be reported which assess content validity of an endoscopic index by demonstrating that the components of the index are sufficient to measure disease activity in Crohn's disease. Content validation is generally based on qualitative assessment. For example, evidence of content validity includes expert panel opinion on face validity, or a systematic review of the literature supporting the development of an endoscopic index.

Studies will be reported which assess criterion validity by demonstrating the degree to which EI scores are an adequate reflection of true Crohn's disease activity as assessed against measurements of gold standard of disease activity. The lack of a single gold standard for Crohn's disease activity is a limitation of these assessments. Studies of predictive criterion validity will be reported which compare whether or not the score predicts true Crohn's disease activity as measured by objective measures of inflammation including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal lactoferrin or fecal calprotectin. Studies of criterion validity which compare endoscopic scores with sequelae in the future, such as surgery, or disability will also be reported. Statistical parameters reported for agreement between the “EI and disease gold standards” will be assessed (i.e., sensitivity or specificity, receiver operating characteristic (ROC) curve, area under the receiver operating characteristic curve (AUC), mean difference, weighed kappa, Spearman's r squared, and the ICC).

Studies will be reported which assess construct validity of endoscopic indices, which acknowledge the limitation of the lack of a gold standard for disease activity and assess how the endoscopic indices are consistent with other hypotheses of true disease activity. Studies of construct validity of the endoscopic index will be reported if they measured the correlation between the endoscopic index score and clinical disease activity indices (e.g. CDAI), or physician global assessment of severity. The minimal clinically important difference (MCID) and appropriate cut-off values to determine active and inactive disease states, clinical response and clinical remission will be examined.

Responsiveness: Changes in the endoscopic index scores following a treatment of known efficacy will serve as an assessment of responsiveness, and the ability of the index to detect change. Responsiveness will be quantified using indicators of effect size or its functions (Zou 2005) or the use of ROC curves to describe how well various score changes can distinguish improved from unimproved patients (Deyo 1991).

Feasibility: Feasibility will be assessed as rater evaluation of the ease of administration and time required for scoring.

Search methods for identification of studies

Electronic searches

A computer aided search will be conducted using the following databases:

1. MEDLINE (1966 to date);

2. EMBASE (1980 to date); and

3. Cochrane CENTRAL Register of Controlled Trials (Issue 7, 2013).

We will perform a search of the MEDLINE and EMBASE databases using the following search strategy:

1. (crohn* or inflammatory bowel disease*).ti. or (crohn* or inflammatory bowel disease*).ab.

2. (mucosal adj2 healing).ti. or (mucosal adj2 healing).ab.

3. (endoscop* adj3 improv*).ti. or (endoscop* adj3 improv*).ab.

4. (mucosal adj2 improvement).ti. or (mucosal adj2 improvement).ab.

5. (endoscop* adj3 respon*).ti. or (endoscop* adj3 respon*).ab.

6. endoscopic remission.ti. or endoscopic remission.ab.

7. stable remission.ti. or stable remission.ab.

8. deep remission.ti. or deep remission.ab.

9. steroid-free.ti. or steroid-free.ab.

10. (clinical adj4 remission).ti. or (clinical adj4 remission).ab.

11. (clinical adj4 endpoint*).ti. or (clinical adj4 endpoint*).ab.

12. (disease* adj4 outcome*).ti. or (disease* adj4 outcome*).ab.

13. (crohn's disease activity index or cdai).ti. or (crohn's disease activity index or cdai).ab.

14. (simple endoscopic score or ses-cd).ti. or (simple endoscopic score or ses-cd).ab.

15. (crohn's disease endoscopic index of severity or cdeis).ti. or (crohn's disease endoscopic index of severity or cdeis).ab.

16. rutgeerts score.ti. or rutgeerts score.ab.

17. capsule endoscopy.ti. or capsule endoscopy.ab.

18. endoscop*.ti. or endoscop*.ab.

19. 1 and (or/2-18)

20. (validation or validated or validating).ti. or (validation or validated or validating).ab.

21. correlat*.ti.

22. 20 or 21

23. 19 and 22

Searching other resources

We will perform a manual review of bibliographies and abstracts submitted to major gastroenterology meetings (2000 to present) including:

1. Digestive Disease Week (DDW);

2. United European Gastroenterology Week (UEGW); and

3. European Crohn's and Colitis Organization (ECCO).

Reference lists from retrieved articles will be scanned to identify additional citations that may have been overlooked by the database search.

Data collection and analysis

Selection of studies

Two authors (RK and JKM) will independently review the titles and abstracts of the studies identified from the literature search. The full text of potentially relevant citations will be reviewed for inclusion and the study investigators will be contacted to clarify any unclear data. Any disagreements will be resolved by discussion and consensus with a third author (BGF).

A standardized form will be used to assess eligibility of trials for inclusion in the study. Each item on the form will be scored as Yes, No or Unclear. The following items will be assessed:

a) Diagnosis of Crohn's disease; and

b) Assessment by CDEIS or SES-CD. 

Data extraction and management

A standardized form will be used to extract information from selected studies. Two authors (RK, JKM) will independently extract and record data. The following data will be recorded from each eligible study: 

a) Number of patients enrolled, number of patients per treatment arm;

b) Patient characteristics: age and gender distribution;

c) Endoscopic index: CDEIS or SES-CD;

d) Cut-off points in the CDEIS or SES-CD associated with clinical response or remission; and

e) Outcomes: intra-rater reliability; inter-rater reliability; responsiveness; validity; feasibility; construct validity; criterion validity, and the MCID.

Assessment of risk of bias in included studies

We will use the following criteria to appraise the risk of bias of included studies:

  • Blinded design

Measures of the effect of the methods

Descriptive statistics will be used to report the validation outcome data. Frequencies and percentages will be shown for categorical variables.

Dealing with missing data

Where possible, authors will be contacted to provide any missing information.

Sensitivity analysis

Sensitivity analyses will include a repeated analysis excluding: (1) unpublished studies; and (2) studies of low methodological quality.

Acknowledgements

Funding for the IBD/FBD Review Group (September 1, 2010 - August 31, 2015) has been provided by the Canadian Institutes of Health Research (CIHR) Knowledge Translation Branch (CON - 105529) and the CIHR Institutes of Nutrition, Metabolism and Diabetes (INMD); and Infection and Immunity (III) and the Ontario Ministry of Health and Long Term Care (HLTC3968FL-2010-2235).

Miss Ila Stewart has provided support for the IBD/FBD Review Group through the Olive Stewart Fund.

What's new

DateEventDescription
26 September 2013AmendedProtocol title changed to correct format

Declarations of interest

Reena Khanna, Geert D'Haen's, Kenneth A Baker and GY Zou have no known conflicts.

Brian Feagan has received lecture fee(s) from: GlaxoSmithKline, Procter & Gamble Pharmaceuticals, Salix Pharmaceuticals Inc, Shire Pharmaceuticals Inc, Tillotts Pharma AG and Merck. All of these financial activities are outside the submitted work.

All potential conflicts of interest for William Sandborn have been noted on the online COI form. All of these financial activities are outside the submitted work.

John MacDonald has received fees for consultancy from Tillotts Pharma AG. All of these financial activities are outside the submitted work.

Barrett Levesque has received fees for consultancy from Santarus, Prometheus Labs, and Castlight Health; lecture fees from Warner Chilcott, Abbott Labs, Salix and UCB Pharma; and travel support from Curatio CME, and the American Academy of Insurance Medicine.All of these financial activities are outside the submitted work.