Fecal Microbiota Transplantation

1 Fecal Microbiota Transplantation Final evidence report September 30, 2016 Health Technology Assessment Program (HTA) Washington State Health Care Authority PO Box 42712 Olympia, WA 98504-2712 (360) 725-5126 Fecal Microbiota Transplantation Provided by: Spectrum Research, Inc. Prepared by: Robin Hashimoto, PhD Andrea C. Skelly, PhD, MPH Erika Brodt, BS September 30, 2016 With assistance from: Krystle Pagarigan, BS Eric Schnell, BS Mark Junge, BS Erin Anthony-Fick, BS Elena Dodge, BSWA Health Technology Assessment September 30, 2016 Fecal Microbiota Transplantation : Final evidence report i This technology assessment report is based on research conducted by a contracted technology assessment center, with updates as contracted by the Washington State Health Care Authority.

2 This report is an independent assessment of the technology question(s) described based on accepted methodological principles. The findings and conclusions contained herein are those of the investigators and authors who are responsible for the content. These findings and conclusions may not necessarily represent the views of the HCA/Agency and thus, no statement in this report shall be construed as an official position or policy of the HCA/Agency. The information in this assessment is intended to assist health care decision makers, clinicians, patients and policy makers in making sound evidence-based decisions that may improve the quality and cost-effectiveness of health care services.

3 Information in this report is not a substitute for sound clinical judgment. Those making decisions regarding the provision of health care services should consider this report in a manner similar to any other medical reference, integrating the information with all other pertinent information to make decisions within the context of individual patient circumstances and resource availability. WA Health Technology Assessment September 30, 2016 Fecal Microbiota Transplantation : Final evidence report ii TABLE OF CONTENTS EXECUTIVE SUMMARY ..1 1. APPRAISAL .. 25 BACKGROUND AND RATIONALE .. 25 KEY QUESTIONS .. 26 OUTCOMES ASSESSED .. 28 WASHINGTON STATE UTILIZATION AND COST DATA.

4 32 2. BACKGROUND .. 33 EPIDEMIOLOGY AND BURDEN OF DISEASE .. 33 CONDITIONS OF INTEREST .. 33 C. difficile infection (CDI) .. 33 Inflammatory Bowel Disease .. 34 TECHNOLOGY: Fecal Microbiota Transplantation (FMT) .. 35 Indications .. 35 Donor Selection .. 35 FMT Procedure .. 36 Proposed Benefits .. 37 Consequences and Adverse Events .. 37 FDA 37 COMPARATOR TREATMENTS .. 38 Treatment Alternatives for CDI .. 38 Treatment Alternatives for IBD .. 38 CLINICAL GUIDELINES .. 39 PREVIOUS SYSTEMATIC REVIEWS/TECHNOLOGY ASSESSMENTS .. 44 MEDICARE AND REPRESENTATIVE PRIVATE INSURER COVERAGE POLICIES .. 61 3. THE EVIDENCE .. 66 METHODS OF THE SYSTEMATIC LITERATURE REVIEW.

5 66 Objectives .. 66 Key Questions .. 66 Inclusion/exclusion criteria .. 66 Data sources and search strategy .. 68 Data extraction .. 70 Quality assessment: Overall Strength of evidence (SoE), Risk of Bias, and QHES evaluation .. 70 Analysis .. 71 4. RESULTS .. 72 Number of studies retained .. 72 KEY QUESTION 1: EFFICACY AND EFFECTIVENESS OF FMT COMPARED WITH ALTERNATIVE TREATMENTS .. 72 Clostridium difficile Infection (CDI) .. 72 FMT vs. Antibiotics for CDI .. 72 FMT vs. Placebo for CDI .. 80 FMT for CDI: Case 83 Inflammatory Bowel Disease (IBD).. 84 FMT vs. Placebo for IBD .. 84 WA Health Technology Assessment September 30, 2016 Fecal Microbiota Transplantation : Final evidence report iii FMT for IBD: Case Series.

6 90 KEY QUESTION 2: EFFICACY AND EFFECTIVENESS OF FMT ACCORDING TO ROUTE OF ADMINISTRATION, TIMING OF ADMINISTRATION, OR TYPE OF PREPARATION .. 91 Number of studies retained .. 91 Clostridium difficile Infection (CDI) .. 91 Route of FMT Administration for Recurrent CDI .. 91 Timing of FMT Administration for Recurrent CDI .. 94 Type of Feces Preparation used in FMT for Recurrent CDI .. 95 KEY QUESTION 3: SAFETY .. 101 Number of studies retained .. 101 Clostridium difficile Infection (CDI) .. 101 FMT vs. Antibiotics for recurrent CDI .. 101 FMT vs. Placebo for recurrent CDI .. 103 Route of FMT Administration for recurrent CDI .. 104 Timing of FMT Administration for Recurrent CDI.

7 104 Type of Feces Preparation used in FMT for Recurrent CDI .. 105 FMT for recurrent CDI .. 105 Inflammatory Bowel Disease (IBD).. 106 FMT vs. Placebo for IBD (UC) .. 106 FMT for IBD .. 108 KEY QUESTION 4: DIFFERENTIAL EFFICACY AND HARMS IN SUBPOPULATIONS .. 109 Number of studies retained .. 109 Clostridium difficile Infection (CDI) .. 109 Type of Preparation: Fresh versus Frozen Feces for FMT .. 109 KEY QUESTION 5: COST EFFECTIVENESS .. 110 Number of studies retained .. 110 Cost Effectiveness of FMT for 110 5. CONCLUSIONS AND STRENGTH OF EVIDENCE (SOE) SUMMARY TABLES .. 118 STRENGTH OF EVIDENCE SUMMARY: FMT VERSUS VANCOMYCIN FOR RECURRENT CDI.

8 120 STRENGTH OF EVIDENCE SUMMARY: FMT VERSUS PLACEBO FOR RECURRENT 122 STRENGTH OF EVIDENCE SUMMARY: FMT VERSUS PLACEBO FOR IBD (UC) .. 123 STRENGTH OF EVIDENCE SUMMARY: COMPARISONS OF FMT ADMINISTRATION ROUTES .. 125 STRENGTH OF EVIDENCE SUMMARY: COMPARISONS OF TIMING OF FMT ADMINISTRATION .. 127 STRENGTH OF EVIDENCE SUMMARY: COMPARISONS OF Fecal PREPARATIONS .. 128 STRENGTH OF EVIDENCE SUMMARY: SAFETY OF FMT FOR CDI .. 129 STRENGTH OF EVIDENCE SUMMARY: SAFETY OF FMT FOR IBD .. 136 STRENGTH OF EVIDENCE SUMMARY: DIFFERENTIAL EFFICACY AND SAFETY RESULTS .. 139 STRENGTH OF EVIDENCE SUMMARY: COST EFFECTIVENESS .. 142 REFERENCES .. 143 WA Health Technology Assessment September 30, 2016 Fecal Microbiota Transplantation : Final evidence report iv TABLES Table 1.

9 Outcome measures used in included 28 Table 2. Summary of Clinical Guidelines .. 40 Table 3. Previous Health Technology Assessments .. 45 Table 4. Selected Previous Systematic Reviews .. 47 Table 5. Overview of payer technology assessments and policies .. 62 Table 6. Summary of inclusion and exclusion criteria .. 67 Table 7. Number of studies included.. 72 Table 8. CDI RCTs comparing FMT to Antibiotics: Study and Patient Characteristics .. 74 Table 9. CDI RCTs comparing FMT to Antibiotics: Additional FMT procedure for CDI recurrence .. 77 Table 10. CDI Cohort Study comparing FMT to Antibiotics: All outcomes .. 80 Table 11. CDI RCTs comparing FMT using Donor versus Autologous (Placebo) Feces: Study and Patient Characteristics.

10 81 Table 12. CDI RCTs comparing Colonoscopic to NG Tube FMT: All outcomes (Lee 2016) .. 82 Table 13. FMT Case Series for patients with CDI: Cure .. 83 Table 14. Ulcerative colitis RCTs comparing FMT to Placebo: Study and Patient Characteristics .. 86 Table 15. FMT vs. Placebo for Active Ulcerative Colitis: Clinical remission and response rates .. 88 Table 16. FMT vs. Placebo for Active Ulcerative Colitis: Symptom improvement and quality of life outcomes (Moayyedi 2015) .. 89 Table 17. CDI RCTs comparing Colonoscopic to NG Tube FMT: Study and Patient Characteristics .. 92 Table 18. CDI RCTs comparing Colonoscopic to NG Tube FMT: All outcomes .. 93 Table 19. CDI Cohort Study comparing FMT after 2 versus 3 recurrences: All outcomes.