Gastroparesis

Gastroparesis delays gastric emptying without a physical blockage.¹ Its symptoms are nausea, vomiting, early satiety, bloating, abdominal pain, and postprandial fullness.² Its prevalence is estimated to be 9.6 per 100,000 among men and 37.8 per 100,000 among women.² Between 1.5 and 3 million Americans are affected. Related hospitalizations increased by 158 percent between 1995 and 2004.³ Evaluation may employ gastric emptying scintigraphy, antroduodenal manometry, and the wireless motility capsule (WMC) – and it guides nutritional, medical, and surgical therapies.

Constipation

Constipation is common, occurring in 15 to 20 percent of the population.^4-6 It is defined as fewer than two bowel movements per week, or a decrease in a person's normal frequency accompanied by straining, difficulty defecating, or passage of hard stools.⁴ Patients with slow-transit constipation often have severe symptoms, with prolonged intervals between bowel movements, and may be refractory to standard therapies. Prevalence of slow-transit constipation is 0.03–0.17 percent.⁷ For patients with refractory symptoms, colonic physiology testing may include radiopaque markers (ROM), colonic scintigraphy, manometry, and the WMC.^8,9

Objectives of the Systematic Review

The WMC is a new modality for diagnosing gastric and colonic motility disorders. The Johns Hopkins Evidence-based Practice Center recently completed an Agency for Healthcare Research and Quality (AHRQ)-funded systematic review of the effectiveness of WMC compared with other tests of gastric and colonic motility (see analytic framework, Figure A). We also sought to define populations that would benefit most from motility testing.

Figure A

Analytic framework of the comparative effectiveness of diagnostic technologies for evaluating gastroparesis and constipation. KQ = Key Question

In the systematic review of this topic, we formulated Key Questions (KQ), reviewed the literature extensively, and obtained feedback from experts. The results are summarized in Table A.

Table A

Summary of the results from the systematic review on the wireless motility capsule.

Overall, the strength of evidence regarding the ability of WMC to detect gastroparesis or slow-transit constipation was graded as low (see KQs listing in Table A). The main limitations were inconsistencies in reporting the performance of motility testing modalities. Great variability existed in administering diagnostic tests and in assessing those tests. No uniform standards define differences in diagnostic accuracy, so we arbitrarily chose a 10 percent difference in sensitivity or specificity for reference standards, such as gastric scintigraphy, and device concordance for non-reference standards, such as ROM.

Most of the “normal” subjects upon which the tests were validated were college-age men, while most of the patients with suspected gastroparesis or constipation were women over the age of 50 years. Since the population of interest comprised motility patients, we excluded studies that included only nondiseased participants.

The major strength of the review was its comprehensiveness. We reviewed abstracts, queried industry sources for unpublished studies, and contacted study authors for missing data.

Conclusions of the Systematic Review

WMC is comparable to other modalities in use for detecting delayed gastric emptying and slow-transit constipation. Data are insufficient to determine the optimal timing of WMC in diagnostic algorithms.

Evidence Gap Identification

Evidence gaps were identified in the review writing process based on the strength of evidence, applicability, and limitations of the review. Individuals who contributed to review writing met multiple times and circulated by email lists of potential questions to identify gaps. This process developed a list of research gaps to be presented to the stakeholders.

Stakeholder Engagement for Additional Gap Identification and Prioritization

External Literature Searches

To identify ongoing clinical trials that may have addressed our Key Questions, we searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and clinicaltrials.gov for trials registered since the search cutoff date of the review.

Knowledge Gaps

Using the information from the systematic review of the comparative effectiveness of WMC testing, knowledge gaps were identified in numerous areas with low strength of evidence. The reason that most strength of evidence (SOE) was low was a lack of fundamental knowledge about WMC measurements—for both normal patients and those with suspected or documented motility disorders, as well as a lack of fundamental knowledge about scintigraphy, manometry, and ROM measurements. The range of WMC values in normal patients, those suspected of motility disorders, and those with documented motility disorders is undefined. These foundational gaps may need to be addressed before clinical gaps can be addressed productively. Therefore, the EPC team identified not only clinical knowledge gaps derived directly from the Key Questions of the review (Table B), but also methodological gaps in the foundational knowledge of test results from normal and diseased patients (Table C).

Table B

Wireless motility capsule stakeholder prioritized clinical knowledge gaps.

Table C

Wireless motility capsule stakeholder prioritized methodological knowledge gaps.

The gap topics and questions were reviewed by the stakeholder panel in two lists to allow them to comment, suggest and rank important issues for both the directly important clinical issues, and the foundational and methodological questions.

The clinical research gaps (Table B) were framed to reflect the clinical gaps in the main evidence report more specifically as relevant to clinical providers. The highest ranked question reflected the uncertainty in the role of the WMC in outcomes for patients with presumed gastroparesis and the role of the WMC as a replacement test versus adjunct test for diagnosis. Consensus guidelines suggest that WMC testing is a replacement for current testing methods, however additional research would lend more weight to that argument. It is currently very difficult in active practice to get access to the WMC for some patients due to lack of insurance coverage, but further research might be more convincing to payers that there is a benefit in this new test and might enable greater access to the WMC. This is clearly a high priority.

The other top ranked question asked whether these same patients with suspected gastroparesis would have comparable results from scintigraphy, anteroduodenal manometry, plain x-ray after marker blind capsule ingestion, endoscopy, or a combination of tests. Similarly, the next ranked questions asked to identify which test should serve as the gold standard or reference standard for comparison, and whether a confirmatory test is required after use of the WMC. Reproducibility of the WMC was also thought to be important and ties into the previous questions which tried to establish the role of WMC testing. Beyond these questions on gastroparesis, the next set of questions focused on slow-transit constipation, including establishing the role of WMC testing in diagnosis compared with other standard tests for ability to diagnose, as well as accuracy and safety in diagnosis.

The next series of questions asked about the incremental value of WMC testing in addition to other testing methods for gastric emptying delay and slow-transit constipation. Interestingly, the top tier included questions about correlating pathology with clinical history and WMC findings. This echoes the questions from the foundational side asking about the same correlation. Also, a focus was the role of WMC testing in colonic dysmotility to predict outcomes, or to predict the effects of medical and/or surgical therapy on outcomes.

The most highly ranked foundational questions (Table C) made clear that basic data ranges for WMC testing have yet to be firmly established in non-diseased populations and those with suspected gastric or colonic dysmotility. With better established norms for diseased and non-diseased patients, there can be better framing of future questions and research endeavors. The next most highly ranked questions were very similar to the initial research questions addressed in our evidence report, which had only low strength of evidence. With additional high quality research, the panel thought that the strengths and weaknesses of WMC testing would be more apparent. Thus, they suggested a priority area for research would be future studies that focus on establishing the role of WMC testing comparatively with scintigraphy, manometry, and radiopaque markers or that focus on obtaining information about test failure and the need for additional tests. It was also considered important to assess diagnostic accuracy of the test when used by non-academic specialists or as a front-line test. Other priority items included establishing the thresholds of diagnostic accuracy and establishing the basic science connection between WMC results and histopathological findings from patients with known disease, if one exists. All of these basic foundational questions were ranked highly by participants in both rounds. These are by definition high-priority areas for future research.

Research Needs

The gap topics and questions were reviewed by the stakeholder panel in two lists to allow them to comment, suggest and rank important issues for both the directly important clinical issues, and the foundational and methodological questions. We received suggestions for additional research questions, which were solicited at the first round of survey, and then subject to general review at the second round of questions. Our expert panel readily identified these areas as necessary and important during both rounds of feedback and, specifically, they focused on certain questions of greater importance. The global rankings demonstrate a delineation of the most highly valued and frequently chosen topics from the least valued and least frequently selected items. The top half of the priority ranked questions were chosen as the top tier, and are considered the highest priority research needs. Next we developed a list of research questions based on the research needs (i.e., a top tier of prioritized evidence gaps) with sufficient detail for use by researchers and funders (in PICOTS format: population, intervention, comparisons, outcomes, timing, setting), including recommendations on research designs that would best suit each research question (Table D). The clinical questions focus on the basic clinical needs in research on WMC testing. The methodological questions address the relationships of WMC data to other diagnostic test result ranges and to the basic biology of the normal and diseased digestive tract. Other questions address basic research principles needed to study the WMC properly. The answers to the latter questions will provide firm underpinnings for future research.

Table D

Summary of research needs (top tier).

Ongoing Research

We scanned trial registries (Appendix A) for any ongoing clinical trials which may have already addressed these high-priority areas (Appendix B). We found two clinicaltrials.gov references which had already published the results on populations outside of the scope of our review, spinal cord injury patients and critically ill intensive care patients. One clinicaltrials.gov reference was not assessing the role of wireless motility capsule in diagnosis of constipation or gastroparesis, but instead focused on acid measurement. We also identified a funded research protocol, which likely has yet to complete enrollment, regarding effect of medication for constipation on outcomes with wireless motility capsule. We await the outcome of this trial, but it is only representative of one of many treatment modalities available to these patients. No other ongoing research projects were identified which address the questions we designed.