Running head: EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 1. Early Implementation of Capsule Endoscopy in Iron Deficiency Anemia:

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1 Running head: EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 1 Early Implementation of Capsule Endoscopy in Iron Deficiency Anemia: A Cost-Benefit Analysis Winde R. Chambers Texas Woman's University Author Note This Capstone Proposal was prepared by Winde R. Chambers, APRN, FNP, Doctor of Nursing Practice Student, Texas Woman s University Dallas, Texas in partial fulfillment of the requirement for NURS 6303 Professional Capstone Project. Correspondence concerning this article should be addressed to Winde R. Chambers, 156 Kingston Road, Benton, LA windechambers@att.net

2 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 2 Table of contents Abstract Introduction 4 5 Purpose 7 Problem statement 7 Research question 8 Conceptual and operational definitions 9 Definition of terms 9 Conceptual framework Review of Literature Population and sample 23 Implementation 24 Project objectives 24 Timeline 24 Project requirements 25 Instrumentation 25 Data collection 25 End products Project Evaluation Sample Characteristics Capsule endoscopy findings Complications Recommendations Clinical outcomes Results

3 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 3 Discussion of Findings Conclusion Reference 37 Appendix A: Conceptual and Operational Definitions of Variables 41 Appendix B: Flowchart Indicating the Clinical Course for Obscure Gastrointestinal Bleeding 42 Appendix C: Costs based on 2010 CPT codes and 2011 Medicare rates 43 Appendix D: Sample 44 Appendix E: Projected timeline 45 Appendix F: Clinical site research approval letter 46 Appendix G: TWU IRB Approval letter 47 Appendix H: Data collection tools 48 Appendix I: SPSS code book 50 Appendix J: Tables Table 1: Clinical features of the samples Table 2: Capsule endoscopy findings Table 3: Recommendations based on capsule endoscopy findings Table 4: Clinical outcomes following capsule endoscopy Appendix K: Statistical Tables from SPSS

4 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 4 Abstract Diagnosing the cause of obscure gastrointestinal bleeding may take a significant amount of time, which contributes to substantial medical cost. Capsule endoscopy procedures have reported a high diagnostic yield, but evidence regarding the cost-effectiveness of this tool is lacking. This clinical practice inquiry evaluated the efficacy of early intervention of capsule endoscopy on cost effectiveness and clinical outcomes. This retrospective study included 132 patients (74 women, 58 men with a mean age of 65.6 years, SD= 6.8) with iron deficiency anemia and/or obscure occult gastrointestinal bleeding. Positive findings were documented in 40% of the cases with the most common (28%) lesion being angiodysplasias. There was not a significant association (p=0.098) found between capsule endoscopy findings and post capsule endoscopy anemia. A significant difference (p=0.000) in cost for early versus later capsule endoscopy was found. This finding was confirmed by the calculation of an incremental cost-effective ratio that showed that delaying diagnostic intervention with capsule endoscopy, costs an additional $2,819 to identify one positive finding. Findings suggest that early implementation with capsule endoscopy decrease costs and ultimately improve clinical outcomes in patients with iron deficiency anemia.

5 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 5 Early Implementation of Capsule Endoscopy in Iron Deficiency Anemia: A Cost-Benefit Analysis Obscure gastrointestinal (GI) bleeding, which is estimated to occur in approximately 5% of cases (American Gastroenterological Association [AGA], 2007), is characterized by bleeding that persists or recurs without identification of a source on initial evaluation with esophagogastroduodenoscopy (EGD) or colonoscopy. Studies have shown that small bowel sources are detected in 75% of these cases with vascular lesions accounting for 70-80%, of which 30-60% are related to angiodysplasias (Lunsford & Pryor, 2010). Angiodysplasias, also known as angiectasias or arteriovenous malformations, are small vascular abnormalities depicted as dilated thin-walled blood vessels with limited to no endothelial lining. Primarily, these lesions are diagnosed in older adults and can lead to major GI blood loss (AGA, 2007). Benign and malignant small bowel tumors are the second most common cause of small bowel bleeding. Other causes are mucosal and structural abnormalities including ulcerations from non-steroidal anti-inflammatory medications, radiation enteritis, infections, celiac sprue, and Crohn's disease (Lunsford & Pryor, 2010). Capsule endoscopy has revolutionized the diagnosis and management of obscure gastrointestinal bleeding over the past decade. Small bowel (SB) video capsule endoscopy, also known as "PillCam SB," is an ingestible telemetric gastrointestinal capsule imaging system used for visualization of the small bowel mucosa. PillCam SB was initially approved by the U.S. Food and Drug Administration (FDA) in 2001 (Given Imaging, 2010). PillCam SB was invented by Given Imaging Ltd., a company known for innovative diagnostic tools for gastroenterology. The PillCam SB measures 11mm x 26mm in size and weighs less than four

6 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 6 grams. The capsule is able to transmit two images per second, generating approximately 50,000 images during the 8 hour procedure (Given Imaging, 2010). Capsule endoscopy is typically performed in the outpatient setting. After fasting and, in some cases inclusion of a bowel preparation, the patient ingests the capsule, initiating its advance through the gastrointestinal tract by peristalsis. The patient wears a SensorBelt with sensor pads that are adhered to the abdominal surface and connected to a DataRecorder that receives the images. After the procedure, the patient returns the SensorBelt and DataRecorder, so images can be downloaded to a computer station for review. The disposable capsule is excreted naturally (Given Imaging, 2010). Because capsule endoscopy is not invasive, the procedure is relatively safe and convenient. Anesthesia is not required, and patients can continue normal daily activities as the procedure is in progress. Contraindications of capsule endoscopy include known or suspected GI obstructions, strictures, or implantable electromagnetic devices (e.g., pacemakers) and swallowing disorders (Nakamura & Terano, 2008). The major risk with capsule endoscopy is capsule retention. Obscure GI bleeding is the main clinical indication for PillCam SB. Other indications include Crohn's and Celiac disease (Nakamura & Terano, 2008). The American Society for Gastrointestinal Endoscopy Technology Assessment Committee supports the use of capsule endoscopy for evaluation of unexplained iron deficiency anemia (Mishkin et al., 2006). The most frequent cause of iron deficiency anemia is chronic occult gastrointestinal bleeding in men and postmenopausal women. Therefore, when men and post-menopausal women experience iron deficiency anemia, the standard of care is investigation of the gastrointestinal tract (Rockey,

7 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY ). This clinical inquiry project explores the cost and benefit of capsule endoscopy to implement the standard of care. Purpose The purpose of this clinical inquiry was to evaluate the efficacy of early intervention on cost effectiveness and clinical outcomes in patients with iron deficiency anemia related to obscure gastrointestinal bleeding. The study's purpose was consistent with the mission of the gastrointestinal clinic serving as the site for this study. The mission of this practice is to deliver high quality gastroenterology endoscopic services in an efficient and cost conscious manner. Problem Statement Currently, Medicare and private insurers require documentation of normal EGD and colonoscopy within six months to one year prior to capsule endoscopy approval (AGA, 2007). Capsule endoscopy allows visualization of areas of the small bowel that are not reached with conventional endoscopic procedures. Capsule endoscopy has been proven to have a high diagnostic yield, although evidence is lacking regarding clinical outcomes following this innovative diagnostic tool (AGA, 2007). Diagnosing the cause of obscure gastrointestinal bleeding may take a significant amount of time, contributing to substantial medical cost (AGA, 2007). It can take from approximately one month to as long as eight years to diagnose patients with obscure gastrointestinal bleeding with the median time being 2 years (AGA, 2007). Prolonging diagnostic evaluation with capsule endoscopy can significantly add to health care expenditures. Goldfarb, Phillips, Conn, Lewis, and Nash (2002) estimated the average cost associated with diagnosing obscure gastrointestinal bleeding is $33,630. More recent literature, however, asserts these figures are significantly underestimated (AGA, 2007).

8 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 8 In 2005, the International Conference on Capsule Endoscopy published a consensus statement delineating the use of capsule endoscopy as part of the initial evaluation for patients with obscure gastrointestinal bleeding (Pennazio, Eisen, & Goldfarb, 2005). Regardless of the consensus, initial evaluation with capsule endoscopy in patients without gross gastrointestinal bleeding is debatable. Often, traditional management is initiated, which is defined as treatment with iron supplementation, followed by observation and/or repeat endoscopy (Rockey, 2010). Research Questions Two research questions guided this project. Research question 1: Is there an association between capsule endoscopy findings (source of bleeding identified) and post capsule endoscopy anemia (resolved or persistent) in patients with iron deficiency anemia related to obscure gastrointestinal bleeding? Null hypothesis: There is no association between capsule findings and post capsule endoscopy anemia. Directional hypothesis: There is a positive association between capsule endoscopy findings and post capsule endoscopy anemia. Research question 2: What is the efficacy of early implementation capsule endoscopy compared to conventional (later capsule endoscopy intervention) diagnostic evaluation for cost effective care management in patients diagnosed with iron deficiency anemia related to obscure gastrointestinal bleeding? PICO question: In patients with iron deficiency anemia, is early implementation of capsule endoscopy more cost effective than conventional diagnostic evaluation? Null hypothesis: There is no difference in cost of early implementation of capsule endoscopy compared to conventional (later capsule endoscopy intervention) diagnostic evaluation in patients diagnosed with iron deficiency anemia. Directional hypothesis: Early implementation of capsule endoscopy is more cost effective than conventional diagnostic evaluation in patients diagnosed with iron deficiency anemia.

9 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 9 Conceptual and Operational Definitions The intervention was conceptually defined as the diagnostic approach for identifying the source of obscure gastrointestinal bleeding and operationally defined as early implementation of capsule endoscopy (immediate use following initial non-definitive scopes) compared to conventional diagnostic evaluation (trial of iron therapy, repeated endoscopy). Efficacy of early intervention with capsule endoscopy is the outcome, conceptually defined as cost effective care management and operationally defined as incurred procedural costs of early and later intervention with capsule endoscopy. The population of interest was conceptualized as patients diagnosed with iron deficiency anemia and operationalized as adults 50 to 80 years of age diagnosed with iron deficiency anemia. Capsule endoscopy findings were conceptually defined as positive or negative results identifying a source of bleeding. Operationally, capsule endoscopy findings are defined as positive with identification of a lesion capable of bleeding (i.e., angiodysplasias, erosions, and ulcerations) or negative in the absence of abnormal findings. Post capsule anemia is conceptually defined as the persistence of clinically unknown anemia and operationally defined as hemoglobin less than 12 (Leeuwen & Poelhuis-Leth, 2009) (Appendix A). Definition of Terms Obscure Bleeding Obscure bleeding was defined as recurrent gastrointestinal bleeding without identification of a source on initial evaluation with EGD or colonoscopy (AGA, 2007). Obscure bleeding is divided into two categories: obscure occult and obscure overt. Obscure occult bleeding was distinguished by patients with iron deficiency anemia (IDA) and/or documented evidence of positive fecal occult blood test (Rockey, 2010). Obscure overt bleeding was differentiated by

10 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 10 bleeding that is obvious to the naked eye or evident by recurrent melena, hematemesis, or hematochezia (Rockey, 2010). A positive outcome was defined as identification of the source of bleeding and/or resolution of anemia. A negative outcome was defined as a retained capsule, persistent anemia, and/or no definite source of bleeding identified on capsule endoscopy. Procedural Costs Costs were analyzed using a third-party-payer perspective. Specifically, Medicare physician fees and reimbursements were used in this analysis because the majority of patients in this population are covered by Medicare. The 2011 Medicare reimbursement fees were obtained from the Pinnacle Business Solutions, Inc website (Appendix C). This agency is a Centers for Medicare & Medicaid Services (CMS) contracted Part B carrier for Arkansas and Louisiana and Part A fiscal intermediary Arkansas, Louisiana, and Mississippi (Pinnacle Business Solutions, 2011). Currently, the charge fee capsule endoscopy (CPT 91110) is $948.75, and a colonoscopy (CPT 45378) is $ with a facility fee of $ Only direct health care costs from a practice standpoint are utilized. These costs included facility use, professional endoscopic procedures fees, and fees for inpatient and outpatient visits. Indirect health care costs and other therapies for the treatment of IDA are not included in this analysis. Conceptual Framework The overarching framework for this project was a cost-effectiveness analysis. Gold, Siegel, Russell, & Weinstein (1996, p. 3) defined a cost-effective analysis as, "a method used to evaluate the outcomes and cost of interventions designed to improve health". A cost-effective analysis aims to approximate the health status improvement relative to quantity and quality of life and cost necessary to achieve these outcomes (Muennig, 2008). This approach allows

11 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 11 comparison of the cost and effectiveness of two interventions. For this project, the cost and effectiveness of capsule endoscopy and conventional therapies were compared using the approach described by Muennig. Muennig (2008) explained six fundamental elements of a cost-effective analysis: (a) health interventions, (b) competing alternatives, (c) health states, (d) health status, (e) cost, and (f) quality-adjusted life year (QALY). Health interventions consisted of treatments or diagnostic tests that improve quality of life and produce favorable health outcomes, such as less hospitalizations or complex procedures (Muennig, 2008). The competing alternative, commonly referred to as the comparative intervention, is necessary for a cost analysis. In this case, early or later capsule endoscopy are the two options. Health states encompass both negative and positive health conditions. In this study, the health states were presence or absence of iron deficiency anemia relevant to the time to diagnosis of obscure gastrointestinal bleeding, resolution of anemia, and/or gastrointestinal bleeding. Health status is delineated as the sum of all health states, including costs, quality of life, and life expectancy (Muennig, 2008). Quality-adjusted life year is defined as a "year of life lived in perfect health" (Muennig, 2008, p. 7). For the purposes of this study, QALY is not calculated because death as an endpoint is not contextually relevant. Cost encompasses all incurred expense resulting from the intervention, as well as future related medical costs precipitated by the intervention (Muennig, 2008). Costs of the alternative are also considered. An incremental cost-effectiveness ratio (ICER) can be calculated to determine the difference in cost between the two diagnostic management options (Figure 1).

12 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 12 (Cost of intervention 2 - Cost of intervention 1) (Quality-adjusted life expectancy 2 - Quality- adjusted life expectancy 1) Figure 1. Incremental cost-effectiveness ratio calculation. Incremental cost-effectiveness ratio calculation (Carlos, 2004) was utilized in this study. This formula yielded the additional cost required to detect one additional lesion using capsule endoscopy. For the purposes of this project, the conventional therapy was intervention 1 and capsule endoscopy is designated as intervention 2. A flow chart depicting a diagnostic algorithm of the clinical course for obscure GI bleeding is presented (Appendix B). Review of Literature Search for the Evidence PubMed and the Cochrane Library were utilized to search for relevant information and data on the topic. PubMed with access to MEDLINE database was selected because it is the most comprehensive index of medical literature. The Cochran Library was selected because it is the most comprehensive index of medical integrative literature for evidence based practice. The problem posed is one that is frequently encountered in the gastrointestinal setting; therefore, using these three bibliographic databases is a comprehensive approach to identifying published pertinent, and relevant sources of evidence. Searches within the PubMed database were conducted by utilizing the Medical SubHeadings (MeSH). Initially, (Search 1) the term gastrointestinal hemorrhage was searched using MeSH and subheadings of diagnosis, "economics", etiology, and "therapy" to yield 35,344 results. Search 2 addressed the MeSH term capsule endoscopy with the subheading of "economics", methods, "standards", and "utilization," yielding 417 results. Search 3 explored

13 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 13 the MeSH term cost and cost analysis to retrieve 153,127 results. Search strategies to narrow results were then applied. Search 1 and 2 (Search 4) were combined utilizing the Boolean operator AND obtaining 87, results to which limits to publications within the past 5 years, human subjects, adult population within clinical trials, meta-analysis, practice guidelines, and randomized control trials were applied to obtaining 5 relevant results. Similarly, Search 2 and 3 (Search 5) were combined, and five relevant citations were obtained. Searches were also conducted through the Cochrane Library utilizing MeSH descriptors. First, (Search 6) the term "gastrointestinal hemorrhage" was searched selecting the qualifier restrictions of: "diagnosis", and "etiology" to yield 569 hits. Next, (Search 7) the term capsule endoscopy was searched to yield 53 hits. Then, (Search 8) the term cost and cost analysis was searched to obtain 30,443 hits. Searches 6 and 7 (Search 9) were merged using the Boolean operator AND and adding the limits to clinical trials published between 2005 and 2010 to yield 9 hits, 4 relevant. Searches 8 and 9 (Search 10) were combined using the same limitations to yield 6 articles. Overall, the conduct of precise searches of these comprehensive bibliographic databases for medical literature provided access to available, relevant articles addressing the clinical outcomes and cost-effectiveness of capsule endoscopy in obscure gastrointestinal bleeding. Availability of clinical evidence regarding the cost-effectiveness of capsule endoscopy in obscure gastrointestinal bleeding, however, is lacking in the literature. All identified articles were retrieved and evaluated to determine relevance to the proposed research question. Appraisal of the Evidence Clinical outcomes. Hindryckx, Botelberge, De Vos, and Looze (2008) conducted a retrospective study to determine the impact of capsule endoscopy on management and clinical

14 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 14 outcomes of patients with obscure gastrointestinal bleeding. Capsule endoscopy data was collected from the University Hospital of Ghent Belgium from August 2002 to February Follow-up data was obtained through the use of a questionnaire that was sent to the primary gastroenterologist and if needed, to the primary care provider. Follow-up information included additional procedures and treatments following capsule endoscopy, final diagnosis, and clinical outcome of the patient. A positive clinical outcome was defined as no overt bleeding or resolution of anemia. A total of 92 patients with normal upper and lower endoscopy and adequate follow-up information were included in the study. Patients were eliminated if the capsule failed or other technical problems occurred. Patients were divided into two groups: obscure overt and obscure occult bleeding. Obscure overt bleeding was documented in 36 patients with a mean age of 67 and hemoglobin of 7.79 g/dl. Obscure occult bleeding was observed in 56 patients with a mean age of 66.1 and hemoglobin of 8.27 g/dl. Results of the study indicated that capsule endoscopy detected lesions in 55 (59.8%) of the 92 patients. Findings included angiodysplasias (22), active bleeding (14), erosions/ulcerations (13), tumor (2), stenosis (1), jejunal venous malformation (2) and abnormal mucosal pattern (1). Of these, 42 patients (76.4%) had subsequent repeat intervention, consisting of upper endoscopy, ileoscopy, push endoscopy, intraoperative enteroscopy, computed tomography, angiography, or surgery. The other 13 patients (23.6%) had nonspecific therapy, such as iron and blood transfusions or "watchful waiting". Of the 37 patients (40.2%) that had negative endoscopy findings, 11 had subsequent diagnostic procedures including upper endoscopy, colonoscopy, computed tomography, and exploratory laparotomy. The final cause of bleeding was not identified in 14 patients, while 23 were diagnosed with either

15 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 15 Cameron's lesions, gastric antral vascular ectasia (GAVE), carcinoid tumor, lower gastrointestinal angiodysplasias, or non-gastrointestinal sources as the cause of bleeding. Hindryckx et al. (2008) determined that long-term clinical outcomes following capsule endoscopy were favorable in 61 (66.3%) patients. The mean follow-up was days. Nearly 34% of patients experienced unfavorable outcomes. Eight (8.7%) patients died during the follow-up period and 15.5% still required transfusions. The credibility of the research findings could be debatable due to the fact that the researchers failed to address the limitations of the study. The researchers concluded that positive capsule endoscopy findings directly impacted the outcomes of patients diagnosed with obscure gastrointestinal bleeding by appropriately guiding subsequent therapy. Toy, Rojany, Sheikh, Mann, and Prindiville (2008) completed a retrospective chart review to assess the impact of capsule endoscopy on clinical management and outcomes. The study included 145 patients that underwent capsule endoscopy at a university hospital from March 2003 to July Indications for capsule endoscopy in this group included obscure overt and occult bleeding, as well as Crohn's disease, abdominal pain, anemia, and miscellaneous. Miscellaneous indications consisted of weight loss, celiac disease, chronic diarrhea, and familial adenomatous polyposis. Patients with obscure gastrointestinal bleeding represented 66% of the sample. The mean age of participants was 55.7 years, with the majority of patients being women (59%). Study results indicated that capsule endoscopy had a diagnostic yield of 69% in the group, with a diagnostic yield of 52.8% in patients with obscure gastrointestinal bleeding. Angiodysplasias (41%) were the most common finding in patients with obscure overt gastrointestinal bleeding, followed by small bowel ulcers (13%). Approximately one-third of patients with obscure gastrointestinal bleeding had positive outcomes, with 37% and

16 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 16 32% in the overt and occult groups, respectively. Capsule retention occurred in six (4%) patients who were evaluated for abdominal pain, Crohn's disease, and anemia. Three patients underwent surgical removal of the capsule. Surgical intervention confirmed patient diagnosis of either Crohn's disease, eosinophilic, or radiation enteritis. Limitations of the study were not identified, however, it was documented that follow-up data was not available for 25 study participants. In this study, capsule endoscopy influenced subsequent management because 61% of patients with positive findings underwent intervention based on findings. There was a statistically significant association between capsule endoscopy findings and positive clinical outcomes. The researchers concluded that the high diagnostic yield generated by capsule endoscopy significantly impacts clinical outcomes. They further confirmed that capsule endoscopy plays a key role, not only diagnostically but with decision making as well. Christodoulou et al. (2007) performed a prospective study to evaluate the reproducibility of capsule endoscopy findings with push endoscopy. Ten patients diagnosed with obscure gastrointestinal bleeding participated in the study. Capsule endoscopy was performed on two consecutive days, and the patients underwent push endoscopy on the third day. The patients completed a survey the day following push endoscopy that assessed discomfort during these procedures and which procedure was preferable. The results of the study showed that a source of bleeding was identified in 60% of the patients with both capsule and push endoscopy. Arteriovenous malformations were found in 40% of the patients. The second capsule endoscopy performed identified one more arteriovenous malformation than the first study. Capsule endoscopy detected an irregular area of small bowel in one patient that was identified as a small bowel tumor on computed tomography. Arteriovenous malformations identified with capsule endoscopy were treated with coagulation with push endoscopy. However, capsule endoscopy

17 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 17 found more lesions (n=18) than were noted with push endoscopy (n=8). The patient survey confirmed that capsule endoscopy was better tolerated than push endoscopy. The researchers concluded that capsule endoscopy findings were highly reproducible on consecutive exams. They further implied that capsule endoscopy should initially be performed after negative upper and lower endoscopy due to the ease, consistency, and reproducibility of this innovative tool (Christodoulou et al., 2007). However, because the researchers did not identify any limitations of the study, the credibility of the research findings could be questionable. Sheibani, Levesque, Friedland, Roost, and Gerson (2009) conducted a retrospective study to evaluate the long-term outcomes following capsule endoscopy in patients diagnosed with iron deficiency anemia compared to those with obscure overt gastrointestinal bleeding. Medical records of patients who underwent capsule endoscopy at the Standford University Hospital and the VA Palo Alto Health Care System was reviewed. One hundred fifty three patients with documented obscure overt gastrointestinal bleeding or iron deficiency anemia with previous negative upper and lower endoscopy were eligible for the study. Of these, 89 agreed to participate and an additional seven were eliminated due to either lack of follow-up, capsule malfunction, or a previously documented source of bleeding. Data was retrospectively collected included the indication for capsule endoscopy, initial hemoglobin and number of blood transfusions, as well as endoscopic and radiological tests performed before and after capsule endoscopy. In addition, the patients were contacted by telephone to determine current health condition and anemia status (Sheibani, Levaesque, Friedland, Roost, & Gerson, 2009). Results of the study showed that capsule endoscopy detected positive findings in 60% of the patients with iron deficiency anemia and 60% in those with overt gastrointestinal bleeding. The most common lesion found was arteriovenous malformations, seen in patients with both iron

18 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 18 deficiency anemia (37%) and overt bleeding (40%). Double balloon endoscopy was documented as the most common, subsequent procedure in 34% of the patients with iron deficiency and in 20% of the overt bleeding group. Patients with iron deficiency anemia that had negative capsule endoscopy findings were noted not to be anemic after 36 months regardless of treatment intervention. The researchers identified limitations, which included the fact that information was not available regarding the onset of bleeding, timing of the capsule endoscopy, medications, and inaccessible prior endoscopy reports. Furthermore, the small sample size restricted statistical analysis and selection bias was precipitated due to the unequal groups. The researchers concluded that conservative therapy may be an appropriate course of action in the majority of patients with iron deficiency anemia (Sheibani, Levaesque, Friedland, Roost, & Gerson, 2009). Laine, Sahota, and Shah (2010) conducted a randomized control trial to evaluate whether capsule endoscopy affected the management and improves the outcomes of patients with obscure GI bleeding. The researchers hypothesized that the improved diagnostic yield of capsule endoscopy would lead to improved outcomes based on a primary endpoint of further bleeding. The study was performed over a period of 5 years in the Los Angeles County and Southern California Medical Center (Laine, Sahota, & Shah, 2010). A total of 136 patients diagnosed with obscure gastrointestinal bleeding (with negative EGD, colonoscopy, and push enteroscopy) were included in the study. Of these, 54 exhibited overt bleeding, and 82 had documented occult bleeding. Patients were randomly assigned to capsule endoscopy (66 patients) or small bowel contrast radiography (53 patients). Results showed a higher diagnostic yield with capsule endoscopy (30%) than with small bowel radiography (7%); however, this did not translate into improvements in overall clinical outcomes. Further bleeding was observed in 30% (20 patients) for those that had capsule endoscopy and 24% (17 patients) for small bowel radiography. The

19 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 19 authors implied that there were no significant improvements in clinical outcomes due to the inability of the capsule to acquire samples and perform therapy. They also postulated that the majority of patients with obscure gastrointestinal bleeding have good outcomes regardless of identifiable abnormalities (Laine, Sahota, & Shah, 2010). Cost- effectiveness. Marmo et al. (2007) conducted a retrospective cohort study comparing the cost effectiveness of capsule endoscopy to other diagnostic procedures. This was the first published cost analysis of capsule endoscopy in patients diagnosed with obscure GI bleeding. Data from January 2003 to October 2005 was collected from nine Italian academic and community hospitals. A total of 369 patients with obscure gastrointestinal bleeding were included in the study. The results compared the ability of capsule endoscopy to detect small bowel pathology to other diagnostic tools, including push enteroscopy, small bowel series, EGD, colonoscopy, angiography, magnetic resonance imaging, ultrasonography, and intraoperative enteroscopy. The primary outcome measure was "effectiveness," characterized as the ability to identify the source of bleeding. The safety of the procedure was the secondary end point. A cost analysis was performed using an incremental cost-effectiveness ratio (Marmo et al., 2007). The source of GI bleeding was found in 58.4% of patients who underwent capsule endoscopy versus 28.0% of patients with other diagnostic procedures (Marmo et. al., 2007). Capsule endoscopy detected angiodysplasias (40.1%), ulcerations and erosions (31.2%), Crohn's disease (10.8%), neoplasias (7.2%), polypoid lesions (7.2%), bleeding with negative findings (2.4%), and colon cancer (0.6%). The mean cost for capsule endoscopy was significantly lower than other diagnostic procedures. The mean cost for a positive diagnosis with capsule endoscopy was $2, compared to $3, for other procedures with a difference of $1, A bootstrap (nonparametric) analysis confirmed that capsule endoscopy was less expensive for

20 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 20 patients undergoing both initial and multiple investigations. The retrospective nature of the study was identified as the major limitation in this study. Other limitations included the potential for inconsistencies among patients and center practices. Patient age and/or presence of comorbidities may have influenced the diagnostic approach, and providers at the different hospitals may have been more or less proficient at performing endoscopic procedures. In addition, the patients included in this study may not have had a definitive diagnosis after undergoing other procedures before capsule endoscopy was performed. It was also considered that patients who were correctly diagnosed were not included in the study, which could yield a lower number of diagnoses with other imaging procedures. Regardless of these limitations, capsule endoscopy was found to be superior over other diagnostic modalities for both diagnostic efficacy and cost effectiveness. The researchers concluded that capsule endoscopy should be employed after a negative EGD and colonoscopy, and the sooner it is performed the better the overall cost and outcome. Gerson and Kamal (2008) performed a decision analysis to estimate the costeffectiveness of capsule endoscopy compared to other diagnostic approaches for obscure gastrointestinal bleeding. A base-case patient and probabilities from previous clinical trials were utilized for this study. A decision tree was created by the use of TreeAge decision analysis software comparing no therapy, push enteroscopy, intraoperative enteroscopy, angiography, initial anterograde double balloon endoscopy, and capsule endoscopy. The cost analysis was calculated based on United States reimbursement rates and according to third-party payers perspectives over a one year time frame. Quality adjusted life years were the primary focus of the analysis. The results of the study showed that double balloon endoscopy was most effective but more expensive than no therapy with an incremental cost effective ratio of $20,833 per

21 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 21 quality-adjusted life year gained. Bleeding cessation was achieved in 86% of the double balloon group, 76% in the capsule endoscopy group, and 59% for no-therapy. The researchers identified limitations, including that probabilities were derived from earlier clinical trials and the short time frame of one year. They also addressed that analysis did not include indirect costs related to the patient, and that quality of life information was lacking in patients with chronic GI bleeding. Interestingly, though researchers confirmed that double balloon endoscopy would be the most cost effective approach due to the capability of detecting and treating lesions during the same session; they reported that the cost for this procedure was unknown. The authors asserted that initial investigation with double balloon endoscopy would increase the work load of gastroenterologists and also pose a higher risk of complications than capsule endoscopy. The researchers further concluded that initial evaluation with capsule endoscopy can reduce the number of unnecessary double balloon procedures and is a cost effective approach compared to other tools when double balloon is not available. Albert et al. (2008) conducted a retrospective analysis to determine the cost effectiveness between capsule endoscopy and double balloon endoscopy. This study had two branches: (a) cost model comparing capsule endoscopy and double balloon endoscopy in diagnosing the source of bleeding and (b) application of the cost model to a group of patients evaluated for obscure gastrointestinal bleeding with these diagnostic tools. A cost minimizing model was used that compared reimbursement costs with overall procedural costs from a facility/practitioner point of view. German diagnostic related groups were used to calculate costs. Cost of equipment and human resources were included in the calculations. The retrospective analysis included 187 patients; 163 patients (87%) initially underwent capsule endoscopy and 24 (13%) had double balloon endoscopy. Capsule endoscopy demonstrated a high diagnostic yield with

22 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY patients (68.1%) having a positive finding, with angiodysplasias (82 or 43.9%) being the most common finding. Of these, 33 patients (40%) subsequently had double balloon endoscopy for coagulation. A source of bleeding was detected in 18 (75%) of those who initially underwent double balloon endoscopy and 14 (77.8%) were treated during the same session. Five of the six patients (83%) with a negative double balloon endoscopy had a subsequent capsule endoscopy that was also negative. The cost model analysis indicated that the break-even point occurred at 100 capsule endoscopies and 79 double balloon procedures. These findings imply that double balloon endoscopy is more cost effective from a provider or hospital standpoint. When applied to the cohort from the retrospective analysis, capsule endoscopy was more cost effective than double balloon endoscopy in obtaining a diagnosis. The researchers identified the major limitations were the retrospective nature of this analysis but acknowledged that a prospective study would have been difficult to conduct due to ethical issues. The researchers concluded that provider costs, procedures per annum, and need for therapeutic intervention with endoscopy significantly influenced procedural cost when comparing these two approaches. They further confirmed that prolonging these investigations can also contribute to increased costs. Overall, the scarcity and lack of specificity of information derived from the literature review justifies the need for further research evaluating the cost-effectiveness of initial investigation with capsule endoscopy in evaluating obscure gastrointestinal bleeding. Research has consistently documented the high diagnostic yield of this tool, but evidence regarding its cost-effectiveness is limited. Current literature suggests that double balloon enteroscopy is more cost-effective compared to capsule endoscopy, as lesions can be identified and treated simultaneously (Albert et al., 2008; Gerson & Kamal, 2008). Double balloon enteroscopy allows

23 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 23 complete visualization of the small intestines using a 200 cm enteroscope with an overtube that measures 140 cm. The endoscopist can maneuver through the small bowel by inflating the over tube balloon and further advancing the endoscope (AGA, 2007). Because patients must be sedated during this procedure, however, double balloon enteroscopy poses a higher risk of complications such as bowel perforation (AGA, 2007). Currently, double balloon endoscopy equipment is not available at the gastrointestinal clinic that is the site for this study or the surrounding area, which provides support for the need to examine early intervention with capsule endoscopy. Population and Sample The study was conducted in a private gastroenterology practice in the southern United States. This practice serves as a primary source for endoscopic services and specialty care for adults with gastrointestinal disorders located in a metropolitan area with a population of 350,471 (United States Census Bureau, 2011). Of these, 44,093 residents are 65 years of age and older (United States Census Bureau, 2011). The practice has performed approximately one thousand capsule endoscopies since FDA approval in A quota sampling method was used for the two independent samples in this project. An effect size of 0.5 was chosen for use in the calculations of the power analysis. Setting a moderate effect size facilitates the detection of the smallest possible effect that will be clinically significant (Cohen, 1992). It is also assumed that this effect size is reasonable, in the sense that an effect of this magnitude could be anticipated in this field of research. Based on a 2-tailed test with a power of 0.8, an effect size of 0.5, and a significance level (alpha) of 0.05, the appropriate sample size for each group was 64. A total of 128 patients were needed for this study. This sample size supports chi square and Mann-Whitney U analyses (Cohen, 1992).

24 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 24 Patients evaluated for iron deficiency anemia from January 2005 to December 2010 were identified in the electronic medical record. Inclusion criteria included men and women ages 50 to 81 diagnosed with iron deficiency and obscure gastrointestinal bleeding. Patients with history of gastric bypass, cases involving obscure overt gastrointestinal bleeding, and those with contraindications for capsule endoscopy were excluded. Premenopausal women with documentation of abnormal menstrual bleeding were eliminated from the study. The intervention group was defined as patients diagnosed with iron deficiency anemia who underwent capsule endoscopy within 6 months of initial EGD and colonoscopy. The conventional group was defined as patients diagnosed with iron deficiency anemia that did not have capsule endoscopy following normal EGD and colonoscopy (Appendix C). Implementation Project Objectives The goal of this clinical inquiry was to evaluate the efficacy of early intervention on cost effectiveness and clinical outcomes in patients with iron deficiency anemia related to obscure gastrointestinal bleeding. Objectives included: (a) evaluating the cost effectiveness of capsule endoscopy; (b) assessing clinical outcomes based on capsule endoscopy findings and resolution of anemia; (c) developing a timely and cost effective practice protocol for the management of patients with iron deficiency anemia; (d) and increasing available evidence to support the development of a clinical practice guideline. Timeline The study was projected to last approximately six months (Appendix C). An expedited application was submitted to the Texas Woman's University (TWU) Institutional Review Board

25 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 25 (IRB) on October 12, The application was approved by the IRB on November 3, Data collection began in December 6, Project Requirements The study site granted permission to conduct the proposed clinical inquiry project based on TWU IRB approval (Appendix D). Approval was obtained from TWU IRB on November 3, 2010 (Appendix E). The primary investigator was assisted by the study site s health information manager to obtain the sample from the electronic medical record. An authorized data collector assisted the primary investigator with data collection. Instrumentation Data collection tools (Appendix F) developed by the researcher were used to collect anonymous data from the patients' electronic medical records. Raw data was collected and documented on these forms. Data was coded as it is entered into Statistical Package of the Social Sciences (SPSS). A SPSS code book was created for this purpose (Appendix G). Data Collection A retrospective chart review of patients diagnosed with iron deficiency anemia was conducted in order to answer the research questions posed. Data collection tools (Appendix F) developed by the researcher were used to collect anonymous data from the patients' medical records. Demographics and pre-procedure hemoglobin, mean corpuscular volume, serum iron, and, total iron binding capacity were recorded for both groups. Results of fecal occult blood testing and prior blood transfusions were documented, if available. Information regarding use of non-steroidal anti-inflammatory (NSAIDs) drugs, antiplatelets, and anticoagulants were obtained for both groups.

26 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 26 For the early intervention group, capsule endoscopy date, findings, and recommendations were recorded. Follow-up laboratory data and clinical outcomes were recorded. For the later intervention group, the length of time from negative EGD and colonoscopy to date of capsule endoscopy were recorded. The number of endoscopic procedures including EGD, colonoscopy, enteroscopy were collected. A positive outcome was defined as identification of the source of bleeding and/or resolution of anemia. A negative outcome was defined as retained capsule, persistent anemia, and/or no definite source of bleeding identified on capsule endoscopy. End Products The results of the study were discussed with the health care providers and personnel at the gastroenterology practice. These findings will aid in the development of a timely and cost effective practice protocol for the management of patients with iron deficiency anemia. A copy of the written documents was provided to the practice partners by the researcher. Findings from this study will increase available evidence to support the development of clinical practice guidelines for the practice. Benefits of placement of capsule endoscopy immediately after conventional endoscopic evaluation in diagnostic algorithms for iron deficiency anemia were determined for all stakeholders. Early placement can reduce losses in productivity and quality of life for patients as evidenced by decreasing time off from work for unwarranted testing and preparation for endoscopic procedures. Providers can benefit by improved diagnostic precision and enhance patient satisfaction in care provided. Project Evaluation Sample Characteristics A retrospective chart review of 425 patients that received capsule endoscopy between January 2005, to December 2010, was performed. Of these, 132 patients met the inclusion

27 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 27 criteria. A total of 293 charts were excluded due to age, history of gastric bypass, gastrectomy, or known Crohn's disease. Cases with evidence of peptic ulcer disease or angiodysplasias noted on previous endoscopy and those involving obscure overt gastrointestinal bleeding with clinical evidence of melena or hematochezia were also excluded. Patients were divided into two groups: (1) patients initially evaluated with capsule endoscopy following negative EGD and colonoscopy (interventional group, n=99), and (2) patients who were previously evaluated for iron deficiency and did not have capsule endoscopy performed during initial evaluation (conventional group/later intervention, n=33). Clinical features of the sample are outlined in Table J1. The intervention group consisted of 99 patients with a mean age of 65.2 and a standard deviation of 6.2 years. Of these patients, 46 were men and 53 were women. The conventional group consisted of 33 patients with a mean age of 66.7 and a standard deviation of 8.3 years. Of these patients, 12 were men and 21 were women. The majority (80.3%) of patients in both groups were Caucasian. The overall mean hemoglobin was 9.9 g/dl with a standard deviation of The majority of patients (65.3%) were on medications that posed an increased risk of bleeding. Antiplatelet agents (30.5%) were among the most frequently documented medications, followed by non-steroidal anti-inflammatory drugs (NSAIDs, 28%) and anticoagulants (6.8%). Capsule endoscopy findings. Overall, capsule endoscopy detected a positive finding (source of bleeding) in 53 (40%) cases. The most frequent lesions identified were angiodysplasias (28%), followed by small bowel ulcerations (6.8%), and erosions (3%). A small bowel stricture (0.8%) was found in one patient who was eventually diagnosed with Crohn's disease. Fresh blood (0.8%) and superficial red mucosa (0.8%) were each noted in one patient without a definitive source of bleeding noted. Non-pathological findings included a submucosal nodule, phlebectasia, and lymphangiectasias (Table J2).

28 EARLY IMPLEMENTATION OF CAPSULE ENDOSCOPY 28 Complications. The majority of patients (97%) did not experience any complications from the procedure. The capsule was retained in two patients (1.5%) and they were referred for surgical removal of the capsule. One of the patients was diagnosed with Crohn's disease after undergoing surgical removal and small bowel resection of the strictured area of small bowel. This was proven to be the cause of the iron deficiency anemia. Capsule failure (0.8%) occurred in one patient, and poor preparation (0.8%) was noted in another which limited the ability to visualized the small bowel. Recommendations. Hematology consultation (23.5%), monitoring laboratory data (22%), and iron supplementation (17.4%) were the most frequently documented advice following capsule endoscopy. Repeating upper endoscopy was recommended in eight cases (6.1%) due to the severity of anemia with no small bowel pathology noted on capsule endoscopy. Surgery was recommended in three cases (2.3%) due to retained capsule in two patients. The other patient had a stricture, but the capsule was not retained in that case. Capsule endoscopy was repeated in one patient due to a failed capsule (Table J3). Clinical outcomes. Clinical outcomes were evaluated to determine whether capsule endoscopy made a positive or negative impact on clinical outcomes. The numbers of positive and negative clinical outcomes were almost equal. Nearly 51% of the clinical outcomes were perceived as negative, whereas, 49.2% were positive (Table J4). Patients in the conventional group were required to repeat upper and lower endoscopy prior to evaluation with capsule endoscopy. The mean difference in time between initial evaluation and capsule endoscopy in this group of patients was months with a standard deviation of Due to this criterion, 42 EGDs, 31 colonoscopies, and one enteroscopy