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Research Protocol – Dec. 14, 2010

Comparative Effectiveness of Bariatric Surgery and Nonsurgical Therapy in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m²

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Table of Contents

Background and Objectives for the Systematic Review

Bariatric surgery, also known as weight-loss surgery, is a group of surgical procedures usually performed on people who are morbidly obese—either with a body mass index (BMI) >40 kg/m² or a BMI ≥35 kg/m² with comorbidities such as diabetes—for the purpose of losing weight and preventing future comorbidity. Types of bariatric surgery include laparoscopic adjustable gastric banding (LAGB), which reduces the size of the stomach with an implanted medical device; Roux-en-y gastric bypass (RYGB), which reroutes the small intestine to a small stomach pouch; biliopancreatic diversion with duodenal switch (BPD/DS), which redirects the pancreatic/biliary content flow and constructs a small stomach tube; and sleeve gastrectomy, which removes a portion of the stomach and leaves a narrowed portion in continuity.

Studies show that these procedures cause significant loss of weight. In addition, bariatric surgery such as LAGB and RYGB have been found to be far more effective than conventional nonsurgical therapy at improving diabetes in the short term, especially among patients who are morbidly obese.1-4 While both techniques are now routinely performed laparoscopically and have demonstrated reduced obesity-related morbidity and mortality, malabsorptive procedures (e.g., RYGB) appear to be superior over restrictive procedures (e.g., LAGB) for obtaining weight loss and improvement in diabetes-related outcomes in patients who are morbidly obese.5 A literature search also suggests that LAGB is a less complex procedure, when compared to RYGB, and produces weight loss; however, LAGB may not have as large an effect on diabetes as other bariatric procedures.6,7

Some investigators have postulated that the surgical stapling and exclusion of a portion of the stomach involved in both RYGB and the gastric sleeve may alter neuropeptide levels that play a role in metabolism. Bariatric surgery is costly, however; and as with any surgical procedure, it may be associated with various adverse effects. Furthermore, there have been reports that within 3 to 5 years after laparoscopic gastric banding, as many as one-third of patients are not able to maintain weight loss because of noncompliance with a prescribed diet and other issues.8 LAGB in particular is associated with a number of complications that result in band removal rates as high as 20 to 30 percent.9,10 Some patients even undergo RYGB. The benefits-to-risks ratio in the long term is also a concern: effectiveness and safety data are very limited to support any claims of long-term benefits or risks.

National Institutes of Health (NIH) guidelines from 1991 established the following criteria for patients considering bariatric surgery: individuals with a BMI >40 kg/m² or ≥35 kg/m² with significant comorbidities (following physician-supervised attempts at weight loss).11 The Center for Medicare and Medicaid Services (CMS) has also made a decision to cover bariatric surgery for treatment of comorbidities associated with morbid obesity (BMI ≥35 kg/m²) for a variety of procedure types.12 However, some preliminary studies have shown that patients whose BMI falls below these criteria may also experience similar weight loss and its associated benefits.13 Despite the potential harms associated with bariatric surgery, there is increased advocacy for the coverage of bariatric surgery such as LAGB for metabolic conditions (e.g., type 2 diabetes), even in settings where its use is not fully supported. Several experts have suggested that the minimum BMI requirement for patients with type 2 diabetes undergoing bariatric surgery be lowered (e.g., <35 kg/m²). Nevertheless, CMS has recently decided that it will not cover bariatric surgery for beneficiaries who have type 2 diabetes and a BMI <35 kg/m², specifically for open and laparoscopic RYGB, LAGB, and open and laparoscopic BPD/DS.14

Given the uncertainties (the minimum BMI requirement, comparative effectiveness especially in the long term, potential adverse effects, etc.) pertaining to the bariatric surgical procedures, a review of the relative benefits and harms of the alternative approaches to treatment of metabolic conditions such as diabetes (e.g., LAGB, RYGB, and other new procedures) and traditional medical management of those conditions is needed for patients whose BMI is <35 kg/m². This review should help 1) better understand long-term benefits and harms associated with different treatment approaches; 2) clarify the types of studies that should be done to determine/establish long-term patient benefits; and 3) develop guideline revisions. In the event that data are lacking, an assessment should be made to determine which key variables influence the long-term net benefits when compared to harms to inform the design of future research studies. This assessment could include postsurgical complications, elective removal of the gastric band, and weight maintenance.

The Key Questions

Question 1

  1. What does the evidence show regarding the comparative effectiveness of bariatric surgery for treating adult patients with a BMI of 30.0 to 34.9 kg/m² and metabolic conditions, including diabetes?
  2. Are certain surgical procedures more effective than others (LAGB, gastric bypass, or sleeve gastrectomy)?

Population(s):

 Adults (age 18+) with a BMI of 30.0 to 34.9 kg/m² and metabolic conditions such as diabetes.

Interventions:

Bariatric surgery: LAGB, RYGB, BPD/DS, and sleeve gastrectomy, and associated devices approved by the United States Food and Drug Administration (FDA).  A list of different devices, their manufacturers, and FDA-approved indications is presented in Appendix A.

Comparators:

 Within-group comparisons will be made to address this key question (KQ). The comparators that will be used are alternative surgical procedures including LAGB, RYGB, BPD/DS, and sleeve gastrectomy.

Outcomes:

  • Primary outcomes: 
    • Short-term:
      • Fasting glucose level
      • Hemoglobin A1c (HbA1c)
      • Triglycerides
      • Blood pressure (mm Hg)
    • Long-term:
      • Percentage of patients with sleep apnea
      • Percentage of patients with gastroesophageal reflux disease (GERD)
      • Percentage of patients with resolution/improvement of diabetes
      • Percentage of patients who discontinued antidiabetic medications
      • Percentage of patients who are euglycemic
      • Time to diabetes resolution
      • Weight loss outcomes (change in BMI, percentage of excess weight loss).
    • Secondary outcomes:
      • Health care utilization/economics
      • Quality-of-life measures
    • Adverse events: 
      • Short-term:
        • Mortality
      • Long-term:
        • Mortality
        • Corrective surgery (i.e., band removal, band-to-RYGB conversion)
        • Gastric surgery adverse events: bowel obstruction, incisional hernia
        • RYGB-specific adverse events: anastomosis complications (i.e., staple-line disruption or ulcer), nutritional deficiencies
        • LAGB-specific adverse events: band-related complications (i.e., slippage or leakage), port/tubing complications, gastric complications (i.e., pouch dilatation or erosion)

Timing: 

  • No minimum duration of follow-up for surgical studies
  • Short-term outcomes: 1 year or best available postsurgical intervention 
  • Long-term outcomes: 5 years or best available postsurgical intervention
 

Settings:

 Any setting in which bariatric surgery takes place.

Question 2

What does the evidence show regarding the comparative effectiveness of bariatric surgery vs. conventional nonsurgical therapies for treating adult patients with a BMI of 30.0 to 34.9 kg/m² and metabolic conditions?

Population(s): as described for KQ1

Interventions: as described for KQ1

Comparators: 

Cross-group comparisons will be made to address this KQ. The comparators to be used are conventional nonsurgical therapies (diet, exercise, pharmaceuticals).  A list of different FDA-approved pharmacologic agents, their manufacturers, and FDA-approved indications is presented in Appendix B.

Outcomes:

  • All outcomes for surgical procedures: as described for KQ1
  • The outcomes for nonsurgical therapies include:
    • Primary outcomes: as described for KQ1
    • Secondary outcomes: as described for KQ1
    • Adverse events:
      • Short-term:
        • mortality
        • systemic medical complications (i.e. myocardial infarction, stroke)
        • Long-term:
        • mortality
          • adverse effects of medications
 

Timing: 

  • Minimum duration of follow-up: as described for KQ1
  • Short-term outcomes: 1 year or best available postsurgical or medical intervention 
  • Long-term outcomes: 5 years or best available postsurgical or medical intervention
 

Settings:

Any setting in which bariatric surgery or other weight-loss programs take place.

Question 3

What are the potential short-term adverse effects and/or complications associated with bariatric surgery for treating adult patients with a BMI of 30.0 to 34.9 kg/m² who have metabolic conditions?

Population(s): as described for KQ1

Interventions: as described for KQ1

Comparators: not applicable 

Outcomes:

  • Short-term adverse events:
    • Mortality
    • Other
 

Timing: 

1 year or best available postsurgical intervention

Settings: as described for KQ1

Question 4

  1. Does the evidence show racial and demographic disparities with regard to potential benefits and harms associated with bariatric surgery for treating adult patients with a BMI of 30.0 to 34.9 kg/m² and metabolic conditions?
  2. What other patient factors (social support, counseling, preoperative weight loss, compliance with recommended treatment ) are related to successful outcomes?
 

Population(s):

Demographic subsets of the populations described for KQ1.  Demographic subsets include different racial/ethnic groups, different age groups, and different genders.

Interventions: as described for KQ1

Comparators: not applicable 

Outcomes:

  • Efficacy and effectiveness outcomes: as described for KQ1
  • Outcome measures for harms or adverse events: as described for KQ3 and KQ5 below
 

Timing: as described for KQ1

Settings: as described for KQ1

Question 5

  1. What does the evidence show regarding long-term benefits and harms of bariatric surgery for treating adult patients with a BMI of 30.0 to 34.9 kg/m² and who have metabolic conditions?
  2. How do the long-term benefits and harms of bariatric surgery compare to short-term outcomes (within 1 year after surgery)?

 
Population(s): as described for KQ1

Interventions: as described for KQ1

Comparators: not applicable

Outcomes: as described for KQ1

Timing: as described for KQ1

Settings: as described for KQ1

Analytic Framework

Figure 1 presents the analytic framework for this comparative effectiveness review (CER), with the five key questions depicted within the context described in the previous sections.

First, by using data from clinical trials and large cohort studies, evidence of the benefits and harms of different types of bariatric surgeries and conventional nonsurgical therapies in treating targeted patients (those with metabolic conditions and a BMI of 30.0 to 34.9 kg/m²) will be documented. Both short- and long-term outcomes are included. Two sets of effectiveness comparisons will be conducted: 1) within-group comparisons of LAGB, RYGB, sleeve gastrectomy, and other surgical procedures to answer KQ1, and 2) cross-group comparisons of surgical procedures to conventional nonsurgical therapies (diet, exercise, pharmaceuticals, etc.) to answerKQ2.

Documented short- and long-term benefits and harms of surgical procedures will also be compared to answer KQ3 and KQ5.

Benefits and harms for specific subpopulations (by gender, age, and race/ethnicity) and other patient factors (social support, counseling, preoperative weight loss, compliance with recommended treatment) will be examined and summarized. This will answer key question four.

Methods

A. Criteria for Inclusion/Exclusion of Studies in the Review

Studies will be included that address the populations, interventions, comparators, and outcomes described above. The following study design types will be included: case series, cohort, case control, controlled trail, and other designs. Minimum sample size of the study is two (i.e., individual case report will not be reviewed). Non-English language studies, as long as they meet the inclusion criteria and a proper translator can be identified, will be included in the review. Relevant grey literature will be included. We will not limit the publication date of studies. If considered necessary, study authors will be contacted for additional data.

The following studies will be excluded: 1) studies that did not report any outcomes of efficacy, effectiveness, or safety/adverse events; 2) non-surgical studies with less than 1 year follow-up; 3) background articles; and 4) single case reports.

B. Searching for the Evidence: Literature Search Strategies for Identification of Relevant Studies To Answer the Key Questions.

A librarian has performed the initial literature search. Two trained reviewers—a psychiatrist and a health researcher —will scan the titles/abstracts of the list compiled by the librarian and select studies for full-text screen. For each of the selected studies, reviewers will perform additional reference mining by scanning titles listed in the reference section to identify additional articles to be considered for inclusion. Reviewers will reconcile their selections and make joint decisions according to the inclusion/exclusion criteria outlined above.

Based on discussions among team members (project leader, surgeon, librarian, etc.), the following databases were identified to possibly include relevant studies of interest and thus were selected to perform the initial literature search.

Databases

  • DARE (Database of Abstracts of Reviews of Effects)
  • Cochrane library of systematic reviews
  • CENTRAL (Cochrane Central Register of Controlled Trials)
  • PubMed (National Library of Medicine, includes MEDLINE)
  • EMBASE (Biomedical and pharmacological bibliographic database)
  • CINAHL (Cumulative Index to Nursing and Allied Health Literature)


Other sources

  • Clinicaltrials.gov
  • References of included studies
  • References of relevant reviews
  • Personal files from projects with related topics

Our literature search will focus on identifying controlled trials and large observational studies. Other sources of literature include comments from public and peer reviews and recommendations from our Technical Expert Panel. All the information we gather will be discussed in weekly project meetings in a timely manner. Revisions of search terms and strategies will be updated according to the decisions made at the meetings. Additional studies will be included if they meet the inclusion criteria illustrated above; in rare case when the inclusion/exclusion criteria need to be modified, AHRQ and Technical Expert Panel will be consulted.

C. Data Abstraction and Data Management

Data will be independently abstracted by two researchers trained in the critical assessment of evidence. The following data will be abstracted from included studies: trial name (if applicable), setting, population characteristics (including sex, age, ethnicity, and diagnosis), eligibility and exclusion criteria, interventions (including dose for medications, frequency for exercise programs, and duration of exercise), any cointerventions, other allowed medication, comparisons, and results for each outcome. Intent-to-treat results will be recorded if available.

A statistician will extract data for efficacy/effectiveness outcomes. A surgeon will choose which outcomes are most appropriate to pool for the surgery studies, while a physician expert in weight loss will choose outcomes for the nonsurgical studies. Poolability of data across studies is also important; the physicians, the statistician, and the project team will jointly make the selection based on their professional knowledge and by considering the frequency of an outcome measure as reported for each trial. A minimum of three studies is required for meta-analysis. For each intervention evaluated within a trial, the sample size, mean outcome, and standard deviation will be extracted. If a study does not report a followup mean or if a followup mean cannot be calculated from the given data, the study will be excluded from analysis. For those trials that do not report a followup standard deviation, we will impute one by assigning the average standard deviation from other trials that report the standard deviation for the same outcome. If fewer than two trials with standard deviations are available, then we will impute the followup standard deviation by taking one-fourth of the theoretical range of the scale.

D. Assessment of Methodological Quality of Individual Studies

To assess internal validity of controlled trials, we will abstract data on the adequacy of the randomization method; the adequacy of allocation concealment; maintenance of blinding; similarity of compared groups at baseline and the authors’ explanation of the effect of any between-group differences in important confounders or prognostic characteristics; specification of eligibility criteria; maintenance of comparable groups (i.e., reporting of dropouts, attrition, crossover, adherence, and contamination); the overall proportion of subjects lost to follow-up; important differences between treatments; use of intent-to-treat analysis; postrandomization exclusions; and source of funding. We will define loss to followup as the number of patients excluded from efficacy analyses, expressed as a proportion of the number of patients randomized.

To assess external validity, we will record the number of subjects screened, eligible, and enrolled; the use of run-in and washout periods or highly selective criteria; the use of standard care in the control group; and overall relevance. Funding source will also be abstracted.

To arrive at a quantitative measure for controlled trials, we will use the Jadad scale, which was developed for drug trials. 15 This method measures quality on a scale that ranges from 0–5, assigning points for randomization and blinding and accounting for withdrawals and dropouts. (Across a broad array of meta-analyses, an evaluation of the scale found that trials scoring from 0–2 report exaggerated results when compared with trials scoring from 3–5. 16 The latter scores indicate studies of “good” quality and the former indicate those of “poor” quality.)

For any disagreement that may arise during the quality assessment, issues will be discussed in the project meeting, and group decisions will be made by the research team.

E. Data Synthesis

Our a priori analytic plan is to summarize the evidence for efficacy and effectiveness of surgical procedures for obesity (LAGB, RYGB, sleeve gastrectomy, etc.), firstly making comparisons among the surgical procedures, and then comparing surgical procedures with conventional nonsurgical therapies. The evidence of risks (adverse events) will be summarized for each surgical procedure and nonsurgical therapy.

For the efficacy and comparative effectiveness analyses, we will focus on studies that report outcomes 1) without a minimum length of followup after surgical procedures, and 2) with at least a 1-year follow-up for nonsurgical therapies. Effect sizes will be calculated for each comparison. If all studies within a subgroup use the same scale, then the effect size does not need to be standardized and a mean difference will be calculated. For subgroups where pooling of data is done across several scales, we will calculate an unbiased estimate by using the Hedges’ g for effect size analysis. Because most of the scales used as outcome measures in the pooled analyses are scored so that patients who have severe symptoms have higher scores, a negative effect size indicates that the surgical procedure has greater efficacy than does the nonsurgical therapy.

For trials that are judged sufficiently clinically similar to warrant meta-analysis, we will estimate a pooled random-effects of the overall mean difference in outcome measure. The individual trial mean differences are weighted by both within-study variation and between-study variation in this synthesis.

We will also assess publication bias. Tests will be conducted by using the Begg adjusted rank correlation test,17 and the Egger regression asymmetry test. 18

All meta-analyses will be conducted with Stata statistical software, version 8.2 (Stata Corp., College Station, TX).
For groups of trials not judged sufficiently clinically similar to support meta-analysis, we will perform a narrative synthesis. Major outcomes and findings of the studies will also be presented in tables to compare different interventions.

In both meta-analysis and narrative descriptions, diabetes-related outcomes (e.g., blood glucose) will be the most important outcomes to report. We will also seek input from key informants and Technical Expert Panel by holding conference calls to prioritize relevant outcomes.

F. Grading the Evidence for Each Key Question

We will assess the overall strength of evidence for intervention effectiveness by using guidance suggested by the U.S. Agency for Healthcare Research and Quality (AHRQ) for its Effective Health Care Program.19,20 This method is based loosely on one developed by the Grade Working Group,21 and classifies the grade of evidence according to the following criteria:

High = High confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence on the estimate of effect.

Moderate = Moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of effect and may change the estimate.

Low = Low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the estimate of effect and is likely to change the estimate.

The evidence grade is based on four primary (required) domains and four optional domains. The required domains are risk of bias, consistency, directness, and precision; the additional domains are dose-response, plausible confounders that would decrease the observed effect, strength of association, and publication bias. For this review, we will use both this explicit scoring scheme and the global implicit judgment about “confidence” in the result. Where the two disagree, we use the lower classification.

References

  1. Shekelle PG. Morton SC, Maglione MA, et al. Pharmacological and Surgical Treatment of Obesity, Evidence Report/Technology Assessment No. 103 (Prepared by Southern California–RAND Evidence-based Practice Center under Contract No. 290-02-0003). Rockville, MD: Agency for Healthcare Research and Quality; July 2004. AHRQ Publication No. 04-E028-2.
  2. Neale T. ASMBS: bariatric surgery found superior to drugs in controlling diabetes. Medpage Today 2008 June 18. Available at: http://www.medpagetoday.com/Endocrinology/Diabetes/9866. Accessed December 2, 2010. Exit Disclaimer
  3. Levy P, Fried M, Santini F, et al. The comparative effects of bariatric surgery on weight and type 2 diabetes. Obes Surg 2007;17:1248-56.
  4. Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA 299:316-23.
  5. Angrisani L, Lorenzo M, Borrelli V, et al. Laparoscopic Adjustable Gastric Banding versus Laparoscopic Roux-en-Y Gastric Bypass: 5 years results of a prospective randomized trial. Surg Obes Relat Dis 2007;2:127-32.
  6. Tice JA, Karliner L, Walsh J, et al. Gastric banding or bypass? A systematic review comparing the two most popular bariatric procedures. Am J Med 2008;121:885-93.
  7. Bowne WB, Julliard K, Castro AE, et al. Laparoscopic gastric bypass is superior to adjustable gastric band in super morbidly obese patients: a prospective, comparative analysis. Arch Surg 2006;141:683-9.
  8. Suter M, Calmes JM, Paroz A, et al. A 10-year experience with laparoscopic gastric banding for morbid obesity: high long-term complication and failure rates. Obes Surg 2006;16:829-35.
  9. DeMaria EJ, Sugerman HJ, Meador JG, et al. High failure rate after laparoscopic adjustable silicone gastric banding for treatment of morbid obesity. Ann Surg 2001;233:809-18.
  10. Launay-Savary MV, Slim K, Brugère C, et al. Band and port-related morbidity after bariatric surgery: an underestimated problem. Obes Surg 2008;18:1406-10.
  11. National Institutes of Health. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Washington, DC: US Department of Health and Human Services; September 1998. NIH Publication No. 98-4083.
  12. Centers for Medicare & Medicaid Services. Medicare National Coverage Determinations Manual, Chapter 1, Part 2, Section 100.14. Available at: https://www.cms.gov/manuals/downloads/ncd103c1_Part2.pdf. Accessed December 7, 2010.
  13. Choi J, DiGiorgi M, Milone L, et al. Outcomes of laparoscopic adjustable gastric banding in low BMI patients. Surg Obes Relat Dis 2010;6:367-71.
  14. Centers for Medicare & Medicaid Services Web site. Decision Memo for Surgery for Diabetes (CAG-00497N). February 12, 2009. November 17, 2008. Updated January 14, 2010. Available at: http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?from2=viewdecisionmemo.asp&id=219&. Accessed December 2, 2010.
  15. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996 Feb;17(1):1-12.
  16. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet. 1998 Aug 22;352(9128):609-13.
  17. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994 Dec;50(4):1088-101.
  18. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997 Sep13;315(7109):629-34.
  19. Agency for Healthcare Research and Quality. Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews, Version 1.0. Rockville, MD: Agency for Healthcare Research and Quality; Draft Posted October 2007. Available at: http://effectivehealthcare.ahrq.gov/repFiles/2007_10DraftMethodsGuide.pdf.
  20. Owens DK, Lohr KN, Atkins D, et al. AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—Agency for Healthcare Research and Quality and the Effective Health-Care Program. J Clin Epidemiol 2010;63:513-23.
  21. Atkins D, Best D, Briss PA, et al, for the GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004; 328:1490.

Definition of Terms

  1. Bariatric surgery: Surgery on the stomach and/or intestines to help a person with severe obesity lose weight.
  2. Body mass index (BMI): An individual’s weight in kilograms divided by his or her height in meters squared. It is used to define normal weight, overweight, and obesity.
  3. Gastric bypass: A surgical weight-loss procedure that involves the creation of a small stomach pouch to restrict food intake and construction of bypasses of the duodenum and other segments of the small intestine to cause malabsorption (decreased ability to absorb nutrients from food).
  4. Gastroesophageal reflux disease (GERD): A condition commonly referred to as acid reflux, in which the liquid content of the stomach regurgitates (backs up or refluxes) into the esophagus.
  5. Laparoscopic adjustable gastric banding: A surgical weight-loss procedure that involves the placement of an adjustable belt around the upper portion of the stomach, restricting the size of the stomach and the amount of food it can hold.
  6. Metabolic condition: A constellation of syndromes including impaired fasting glucose (prediabetes) and diabetes mellitus that increase the risk of cardiovascular disease.
  7. Sleep apnea: A disorder characterized by a reduction or pause of breathing (airflow) during sleep.
  8. Sleeve gastrectomy: A surgical weight-loss procedure in which the stomach is reduced to about 15 percent of its original size by surgical removal of a large portion of the stomach.

Summary of Protocol Amendments

In the event of protocol amendments, the date of each amendment will be accompanied by a description of the change and the rationale.

NOTE: The following protocol elements are standard procedures for all protocols.

  1. Review of Key Questions
    For all EPC reviews, key questions were reviewed and refined as needed by the EPC with input from Key Informants and the Technical Expert Panel (TEP) to assure that the questions are specific and explicit about what information is being reviewed. In addition, for Comparative Effectiveness reviews, the key questions were posted for public comment and finalized by the EPC after review of the comments.
  2. Key Informants
    Key Informants are the end users of research, including patients and caregivers, practicing clinicians, relevant professional and consumer organizations, purchasers of health care, and others with experience in making health care decisions. Within the EPC program, the Key Informant role is to provide input into identifying the Key Questions for research that will inform healthcare decisions. The EPC solicits input from Key Informants when developing questions for systematic review or when identifying high priority research gaps and needed new research. Key Informants are not involved in analyzing the evidence or writing the report and have not reviewed the report, except as given the opportunity to do so through the peer or public review mechanism.

    Key Informants must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Because of their role as end-users, individuals are invited to serve as Key Informants and those who present with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any potential conflicts of interest identified.
  3. Technical Experts
    Technical Experts comprise a multi-disciplinary group of clinical, content, and methodologic experts who provide input in defining populations, interventions, comparisons, or outcomes as well as identifying particular studies or databases to search. They are selected to provide broad expertise and perspectives specific to the topic under development. Divergent and conflicted opinions are common and perceived as health scientific discourse that results in a thoughtful, relevant systematic review. Therefore study questions, design and/or methodological approaches do not necessarily represent the views of individual technical and content experts. Technical Experts provide information to the EPC to identify literature search strategies and recommend approaches to specific issues as requested by the EPC. Technical Experts do not do analysis of any kind nor contribute to the writing of the report and have not reviewed the report, except as given the opportunity to do so through the peer or public review mechanism.

    Technical Experts must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Because of their unique clinical or content expertise, individuals are invited to serve as Technical Experts and those who present with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any potential conflicts of interest identified.
  4. Peer Reviewers
    Peer reviewers are invited to provide written comments on the draft report based on their clinical, content, or methodologic expertise. Peer review comments on the preliminary draft of the report are considered by the EPC in preparation of the final draft of the report. Peer reviewers do not participate in writing or editing of the final report or other products. The synthesis of the scientific literature presented in the final report does not necessarily represent the views of individual reviewers. The dispositions of the peer review comments are documented and will, for CERs and Technical briefs, be published three months after the publication of the Evidence report.

    Potential Reviewers must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Invited Peer Reviewers may not have any financial conflict of interest greater than $10,000. Peer reviewers who disclose potential business or professional conflicts of interest may submit comments on draft reports through the public comment mechanism.

Appendix A

Appendix A: List of bariatric surgery devices, manufacturers, and FDA-approved indications
Device Manufacturer FDA Approved Indication(s)
a Only FDA-approved devices will be included in the review.

b The device is not available in the United States. If it used in a research study, the study will be excluded from the review.
Lap-Band Allergan Inc. Weight reduction for severely obese patients who have a body mass index (BMI) of at least 40 kg/m² or a BMI of at least 35 kg/m² with one or more severe comorbid conditions, or patients who are 100 lbs. or more over their estimated ideal weight. Only for severely obese adult patients for whom more conservative weight-reduction alternatives, such as supervised diet, exercise, and behavior modification programs have been ineffective.
Realize (Swedish) Adjustable Gastric Band Ethicon Endo-Surgery, Inc. (part of Johnson & Johnson) Weight reduction for morbidly obese patients with a body mass index (BMI) of at least 40 kg/m² or a BMI of at least 35 kg/m² with one or more severe comorbid conditions. Only for morbidly obese adult patients for whom more conservative weight-reduction alternatives, such as supervised diet, exercise, and behavior modification programs have been ineffective.
Midband Médical Innovation Développement Not approved.b
Heliogast band Helioscopie Not approved.b
A.M.I Soft Gastric Band Austrian Agency for Medical Innovations Ltd. Not approved.b
BIORING Cousin Biotech Not approved. b

Appendix B

Appendix B: List of pharmacologic agents, generic (name brand), manufacturers, and FDA-approved indications
Pharmacologic Class Generic (Name brand) Manufacturer FDA-Approved Indication(s)a
a Only FDA-approved pharmacologic agents will be included in the review.
GLP-1 receptor agonist Liraglutide (Victoza) Novo Nordisk Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Incretin Mimetic Exenatide (Byetta)
  • Amylin Pharmaceuticals
  • Eli Lilly and Company
Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
DPP-4 inhibitor Sitagliptin (Januvia) Vildagliptin (Galvus) Merck & Co Novartis Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Lipase inhibitor Orlistat (Xenical, Alli)
  • Hoffmann La Roche
  • Glaxosmithkline Cons
  • Obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet; to reduce the risk for weight regain after prior weight loss; indicated for obese patients with initial body mass index (BMI) ≥30 kg/m² or ≥27 kg/m² in the presence of other risk factors (e.g., hypertension, diabetes, dyslipidemia).
  • Weight loss in overweight adults, 18 years and older, when used along with a reduced-calorie and low-fat diet.
Norepinephrine, serotonin, and dopamine reuptake inhibitor Sibutramine (Meridia) Abbott Management of obesity including weight loss and maintenance of weight loss in conjunction with a reduced calorie diet; recommended for obese patients with initial body mass index ≥30 kg/m² or ≥27 kg/m² in the presence of other risk factors (e.g., diabetes, dyslipidemia, controlled hypertension).
Sympatho-mimetic amine Diethylpropion (Tenuate) Watson Pharmaceuticals Corepharma Management of exogenous obesity as a short-term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction inn patients with an initial body mass index (BMI) of 30 kg/m² or higher and who have not responded to an appropriate weight-reducing regimen (diet and/or exercise) alone.

Figure 1.

Figure 1. Provisional analytic framework for evaluating the effectiveness and safety of alternative approaches to treatment of metabolic conditions among patients with a BMI of 30.0 to 34.9 kg/m²

The analytic framework for this project begins with the patient whose BMI is between 30 and 34.9 and who has diabetes or other metabolic conditions such as impaired glucose tolerance, and includes assessment of patient-specific factors such as age, gender, social support, BMI, etc.  The patient has treatment options including bariatric surgery (and within this category several different types of bariatric surgery) and medical management (and within this category several different types of medical management).  There are short term benefits and harms of bariatric surgery, each of which is addressed in a separate key question, and these include benefits such as a reduction in diabetes medications needed, improved diabetic control, improved blood pressure control, etc., and short term harms including mortality from the operation and peri-operative complications.  All treatment options have long term benefits and harms.  Key questions assess each of these.

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