cost savings associated with rifaximin for diarrhea-predominant irritable bowel syndrome ·...

ABSTRACT

Objectives: To investigate the estimated cost of 2 strategies for management of diarrhea-predominant irritable bowel syndrome (IBS-D): (1) initial treatment with rifaximin and (2) diagnostic testing followed by treatment.

Study Design: Economic evaluation using decision tree analysis.

Methods: The decision-analytic model compared rifaximin treat-ment fi rst with diagnostic testing fi rst in patients suspected to have IBS-D. The primary end point was the expected cost per treatment pathway. Diagnostic tests included celiac screening, colonoscopy, endoscopy, abdominal computed tomography (CT) scan, and thyroid functions. Monte Carlo simulation was used to compute confi dence intervals (CIs) for cost estimates. Retreatment rates, effi cacy param-eters, and cost assumptions were extracted from published literature and public sources. The base case scenario assumed all diagnostic tests were performed. Sensitivity analyses addressed the impact of variation in parameters on expected costs.

Results: A cost savings of $2401 for the rifaximin-fi rst approach in the base case scenario was predicted. When only the celiac disease test was used, the model predicted a cost savings of $261 for the rifaximin-fi rst approach. The mean cost savings with the rifaximin-fi rst approach in the base case with the Monte Carlo simulation trial was $2398 (95% CI $367-$4974). Variables with the greatest impact on overall expected costs were the cost of rifaximin, colonoscopy, a gastroenterology visit, and abdominal/pelvic CT scans.

Conclusions: This decision-analytic model indicates potential incre-mental savings associated with the use of rifaximin in a therapeutic trial model. This approach represents an important paradigm shift for physicians treating patients with IBS-D.

(Am J Pharm Benefi ts. 2012;4(3):e65-e72)

Original R

esearch

Irritable bowel syndrome (IBS) is a common functional

bowel disorder with a prevalence of up to 16% of the US

population.1,2 It is characterized by symptoms of abdom-

inal discomfort associated with changes in stool frequency

and consistency.3 Because of the chronic, episodic nature

of IBS, many patients do not seek prompt medical attention

and there are a signifi cant number of undiagnosed cases.1,4,5

The prevalence of IBS may also vary based on the diagnostic

criteria used to defi ne the disorder.6 The incidence of new

cases of IBS has been estimated to be 1% to 2% of the gen-

eral population.4,5 IBS manifests itself in 3 major forms: diar-

rhea predominant (IBS-D), constipation predominant, and

a mixed form (IBS-M) of the illness.7 The diagnosis of IBS

involves the identifi cation of key symptoms as well as the

exclusion of other possible illnesses.8,9 Although many treat-

ments are used for IBS, very few have demonstrated effi cacy

versus placebo in appropriately designed trials. The more

common therapeutic approaches include diet and lifestyle

modifi cation (eg, stress reduction, moderate exercise), bulk-

ing agents, antispasmodics, antimotility agents, antidepres-

sants, probiotics, and psychological approaches.2,9

Recently, researchers have found evidence that altered gut

fl ora in the small intestine or the colon leads to the develop-

ment of IBS symptoms, suggesting a role for antibiotics as

an additional therapeutic option for some IBS patients.8,10-12

Neomycin, metronidazole, and clarithromycin have been in-

vestigated for the management of IBS, with mixed results.

However, rifaximin (Xifaxan 550 mg, Salix Pharmaceuticals,

Ltd, Raleigh, North Carolina; currently approved for reduc-

tion of risk of overt hepatic encephalopathy recurrence), a

broad-spectrum, nonabsorbable antibiotic, is signifi cantly

more effective than placebo in both phase II and phase III

trials with respect to global IBS symptoms and bloating in

patients with IBS-D.12,13 Based on these trials, rifaximin is 1

of only 2 treatment options (with tricyclic antidepressants)

strongly recommended by the American College of Gastro-

enterology (ACG).8

At a GlancePractical Implications e66

Author Information e71

Web Exclusive www.ajpblive.com

Cost Savings Associated With Rifaximin for Diarrhea-Predominant Irritable Bowel Syndrome

Mark Pimentel, MD; Philip Schoenfeld, MD, MSEd, MSc Epi; Christopher H. Purdy, MA; Colleen Gilbert, PharmD; and Raf Magar, MBA

www.ajpblive.com Vol. 4, No. 3 • The American Journal of Pharmacy Benefi ts e65

P R A C T I C A L I M P L I C A T I O N S

Irritable bowel syndrome (IBS) is associated with excessive diagnostic testing and expense because of the lack of good, specific diagnostic tests; unnecessary surgeries; and poor response to many treatments.

n In phase III studies, rifaximin improved global symptoms, bloating, abdominal pain, and stool consistency of subjects with diarrhea-predominant IBS (IBS-D).

n Cost analysis comparing a therapeutic trial of rifaximin with the standard approach of diagnostic testing followed by treatment for patients with symptoms of IBS-D suggests that rifaximin first is a more cost-saving strategy.

e66 The American Journal of Pharmacy Benefits • May/June 2012 www.ajpblive.com

n Pimentel • Schoenfeld • Purdy • Gilbert • Magar

Since gastroenterologists commonly consider IBS to

be a diagnosis of exclusion, they routinely perform a se-

ries of diagnostic tests for patients presenting with IBS

symptoms, including thyroid function tests, abdominal

ultrasound or computed tomography (CT) scan, and en-

doscopy and colonoscopy. However, the likelihood of

finding an alternative cause of the abdominal discomfort

and altered bowel habits (eg, Crohn’s disease) is slight.14

In fact, current guidelines from ACG for the management

of IBS only recommend routine screening for celiac sprue

for IBS-D and IBS-M, and specifically recommend against

the routine performance of multiple diagnostic tests.8

The current literature includes only a modest number

of economic evaluations of IBS therapies.15-20 There are

several challenges when evaluating IBS therapies from an

economic perspective. One of the difficulties involves the

large degree of heterogeneity between studies that have

evaluated therapies for the treatment of IBS.21,22 There is

substantial variation with respect to study size, length of

follow-up, and the inclusion criteria for the patient popu-

lation. Direct IBS-related costs and outcomes are seldom

evaluated within a phase II or phase III clinical trial. Cost-

utility analyses are difficult to perform if the overall quality-

of-life scores are not captured within the study.23 IBS is a

chronic disease and can often affect daily activities, includ-

ing work, in terms of both absenteeism and presenteeism.

These indirect costs add an additional layer of complexity

to the economic evaluation of IBS therapies; however, this

aspect underscores the clinical and economic value of suc-

cessful IBS therapies. Burden-of-illness studies corroborate

the breadth of the economic impact of this illness.24,25

The prevalence of IBS places a significant health and

financial burden on the US population. The chronic and

serious nature of the disease symptoms significantly im-

pacts the sufferers both socially and economically. From

an employer perspective, a previous study has indicated

that employees with IBS cost approximately $1251 more

than matched employees without IBS.1 Estimates for the

direct costs attributable to IBS in the United States vary

from $1.5 billion to $10 billion. Similarly, the overall eco-

nomic burden in the United States for indirect costs is very

significant; estimates for this aspect of the burden of IBS

have been as high as $20 billion.24 Despite the magnitude

of these estimates, they may be an underestimate because

they represent the costs associated with patients who seek

care; many people with IBS do not seek medical care.

This economic evaluation investigates the optimal strat-

egy for the utilization of rifaximin and the minimization

of overall cost expenditures from the payer perspective.

The purpose of this economic evaluation is to compare

2 strategies for the management of patients who present

with the symptoms of IBS-D. We compared a strategy that

treats patients with rifaximin prior to diagnostic testing

with a strategy that initiates a series of diagnostic tests

prior to treatment. The economic model is a decision-

analytic model; the primary end point of the decision

analysis is the expected cost per treatment strategy.

METHODSThe economic model was a 2-arm decision-analytic

model. The model compared 2 differing treatment strate-

gies (Figure 1): (1) treatment of suspected IBS-D patients

with rifaximin prior to diagnostic testing versus (2) initia-

tion of a series of diagnostic tests prior to treatment with

rifaximin. Suspected IBS-D patients were identified ac-

cording to their presenting symptoms including abdomi-

nal pain, abdominal discomfort, and bloating, but without

features that might have indicated a more severe problem

(eg, bleeding from bowels, weight loss). IBS-D patients

would typically characterize many of their stools as ei-

ther loose or watery.13 The considered diagnostic tests in-

cluded a celiac screening test, colonoscopy, endoscopy,

abdominal CT scan, and thyroid function tests (Table 1).

The primary end point of the model was the expected

cost per treatment pathway. Probability variables were

modeled as beta distributions; cost variables were mod-

eled as uniform distributions. Monte Carlo simulation (n

= 100,000 trials) was used to compute confidence inter-

vals (CIs) for expected cost estimates. The time horizon

for the decision-analytic model was 1 year. The software

used for analysis was TreeAge Pro Suite 2009 (TreeAge

Software, Inc, Williamstown, Massachusetts).

The retreatment rate used in the model was extracted

from a medical chart review that examined 522 charts

and identified 71 patients retreated with rifaximin for

IBS-D at least once. The study reported that the median

www.ajpblive.com Vol. 4, No. 3 • The American Journal of Pharmacy Benefits e67

Rifaximin Cost Savings for IBS-D

retreatment time was at least 4 months.33

Thus, the analytic model assumed an aver-

age of 3 rifaximin treatments per year and a

range of 2 to 4 treatments per year. The addi-

tional treatments could be the same therapy

(ie, rifaximin) or any other alternate therapy

based on the patients’ clinical response. All

treatment types other than rifaximin were

considered to be chronic. The response

rate for treatment with rifaximin was taken

from phase III clinical trial results.13 The cost

parameters were extracted from published

literature and other public sources (Table

1). Other IBS therapy includes commonly

used prescription and nonprescription phar-

macologic treatments. The probabilities

associated with the likelihood of discover-

ing organic gastroenterologic disease via

specified diagnostic tests were drawn from

published literature. As applicable, the same

assumptions were applied to both treatment

strategies in order to ensure an equitable

comparison.

In order to address the variability associ-

ated with the number and type of diagnostic

procedures that may be utilized, the model

Table 1. Model Inputs: Efficacy and Cost

Input Type and Input Estimate Rangea Reference

Clinical efficacy

Rifaximin therapy 0.41 NA 13

Diagnostic outcomes

Celiac screening 0.04 NA 26

Upper endoscopy 0.013 NA 14

Colonoscopy 0.013 NA 14

Abdominal pelvic CT scan 0.0 NA 14

Thyroid function test 0.06 NA 14

Cost

Celiac screening $525b $420-$630 27

Upper endoscopy $820 $656-$984 28

Colonoscopy $2400 $1920-$2880 29

Abdominal pelvic CT scan $2175 $1740-$2610 29

Thyroid function test $220 $176-$264 30

Rifaximinc $784 $627-$941

Other IBS therapyd $155 $10-$300e 26

Gastroenterology visit $295 $216-$374e 31

Outpatient visit $101 $74-$127e 32

CT indicates computed tomography; IBS, irritable bowel syndrome. aRanges were investigated by sensitivity analysis. bPersonal communication with clinical advisor provided a cost estimate of $650 for celiac testing. Model input was $525, which represents the midpoint value between $400 (Wellsphere) and $650 (personal communication). cRifaximin cost was provided by Salix Pharmaceuticals, Ltd, Raleigh, NC. dOther IBS therapy includes all commonly used pharmacologic therapies. eThe median of a given range was imputed as the parameter estimate.

Figure 1. Decision-Analytic Modela

Suspected IBS Patient

Rifaximin

Success Observation Recurrence

Rifaximin (1 Additional Trt)p2

p5

p6

p7

p3

p4

p5

p2

p3

p4

p6

p7

Rifaximin (2 Additional Trt)


Appropriate Trt

IBS Therapy (1 Trt)

IBS Therapy (2 Trt)

IBS Therapy (3 Trt)

Observation Recurrence




IBS Therapy (1 Trt)

IBS Therapy (2 Trt)

IBS Therapy (3 Trt)

Positive

Diag_Success

Negative

#

Success

Rif_Success

Failure#

Failure Diagnostic Testing

Positive Appropriate Treatment

Diag_Success

Rif_Success

Negative

#

#

Rifaximin

Diagnostic Testing

Diag_Success indicates success of diagnostic testing algorithm; IBS, irritable bowel syndrome; Rif_Success, success of rifaximin algorithm; #, binary node (remainder of probability when one rate is known). a The time horizon for the analytic model was 1 year. The comparison was between 2 differing treatment algorithms: (1) a therapeutic trial of rifaximin prior to diagnostic testing versus (2) diagnostic testing prior to medication therapy (beginning with rifaximin therapy).



was run under various scenarios. The base case scenario

assumed that all diagnostic tests were performed; other

scenarios assumed only a subset of these tests were per-

formed (Table 2). The base case scenario assumed that

rifaximin responders would average 3 treatments with

rifaximin per year. The model assumed an equal distri-

bution of 1, 2, or 3 therapies per year for users of other

IBS therapies. The first scenario investigated the model

results when only the celiac test was utilized prior to

rifaximin therapy, which is consistent with the recent

ACG guidelines.8 The additional scenario investigated the

model results when all tests with the exception of the

celiac test were used. The cost savings was defined as the

difference in expected costs between

treatment strategies (Table 2).

The sensitivity analyses addressed

the impact of variation of individual

variables on the overall outcome of

expected cost (Table 3). The sensi-

tivity analyses investigated cost vari-

ables for a range of ±20%, except

where otherwise noted. If the value

of the cost variable was extracted as

a range, the midpoint of the limits

of the range was imputed. The sen-

sitivity analyses indicate the relative

impact of each variable within the

context of the entire set of cost vari-

able sensitivity analyses.

The following assumptions were

applied to the decision-analytic mod-

el (Figure 1). The comparison was

explicitly between the therapeutic

trials of rifaximin prior to diagnostic

testing and a diagnostic-testing-first

approach. In the rifaximin-first ap-

proach, if the patient responded to

the medication therapy, diagnostic

testing was avoided. If the patient did

not respond to rifaximin, and subse-

quent diagnostic tests did not reveal

organic gastrointestinal (GI) disease,

the patient proceeded to other IBS

therapies. For the diagnostic-testing-

first approach, a series of diagnostic

tests were performed prior to rifaxi-

min therapy. If no organic GI disease

was diagnosed, the patient proceed-

ed to rifaximin therapy. If rifaximin

therapy failed, it was not utilized

again. A gastroenterology visit was assigned each time

a test was performed or a treatment was prescribed. A

lower cost for outpatient visits was imputed for follow-up

visits not requiring additional treatments or tests.

RESULTSThe result of the decision-analytic model indicated in-

cremental cost savings for IBS-D patients using the thera-

peutic trial of rifaximin. For the base case, the tree model

predicted a cost savings of $2401 for patients who were

initially treated with a therapeutic trial of rifaximin. Two

key alternate scenarios were investigated; the first scenario

investigated the cost implications when only the celiac

Table 2. Scenario Testinga

Type and Arm Coursesb Expected Cost Cost Savingsc

Base case

Therapeutic trial 2 $5846 $2456

Standard care 2 $8302

Base case



Base case



Celiac only



Celiac only



Celiac only



Diagnosticd



Diagnosticd



Diagnosticd



aAll amounts are expressed in US dollars. Expected costs were computed based on values listed in Table 1; no sensi-tivity analysis was performed for the cost of rifaximin. bThe average number of courses of rifaximin assumed per patient. cDefined as cost (cost of standard care minus cost of therapeutic trial). dThis scenario included all tests except the celiac screening test (ie, upper endoscopy, colonoscopy, abdominal pelvic computed tomography scan, thyroid function test).



disease test was used. This scenario predicted a cost sav-

ings of $261 for the rifaximin-first treatment approach. The

other scenario investigated the cost implications when all

tests other than the celiac test were used; the therapeutic

trial of rifaximin predicted a cost savings of $2262 in this

situation (Table 2). Other scenarios were investigated for

more or fewer trials of rifaximin per year (ie, 2 or 4).

Monte Carlo simulation was used to provide a distribu-

tion for the incremental outcomes (Figure 2). The mean

value of the simulation trial was $2398 (ie, expected cost

of the standard-of-care approach minus the cost of a ther-

apeutic trial of rifaximin). The 95% CI for the incremental

outcome was $367-$4974 in the base case, indicating that

cost savings with a therapeutic trial of rifaximin is highly

likely (>95%).

Sensitivity analyses were performed to assess the im-

pact of variation in cost variable inputs on the overall

outcome. The variables with the greatest impact on over-

all expected costs were the cost of rifaximin (23.93% im-

pact), the cost of colonoscopy (23.50% impact), the cost

of a gastroenterology visit (22.61% impact), the cost of an

abdominal pelvic CT scan (19.30% impact), and the cost

of other IBS therapies (6.56% impact). The impact of all

other cost variables on the overall outcome of cost was

less than 3% (Table 3 and Figure 3).

DISCUSSIONThis decision-analytic model indicates incremental

savings associated with the use of rifaximin in a therapeu-

tic trial. All scenarios tested were consistent with respect

to the cost savings predicted by this treatment approach.

The cost savings result from the avoidance of diagnostic

tests, which often are not necessary. The Monte Carlo

simulation results indicate a high degree of confidence

that the cost saving is positive for a therapeutic trial of

rifaximin (for the base case scenario).

There are other potential benefits of the rifaximin-

therapeutic-trial approach. While current studies did not

include quality-of-life measures, it is reasonable to pos-

tulate that a more rapid improvement in IBS symptoms

might improve a patient’s health-related quality of life. A

number of studies have confirmed the detrimental effect

of IBS on health-related quality of life, particularly with

increasing severity of IBS symptoms.34,35 An improvement

in symptom severity is therefore likely to make patients

more comfortable in vulnerable situations and generally

improve their sense of well-being.

There are also direct and indirect cost savings advan-

tages for the healthcare payer when expensive diagnostic

tests are avoided. Although the use of many diagnostic

tests is known to yield a low detection rate for other GI

diseases, it is clear that these tests consume a large pro-

portion of healthcare resources by patients with IBS.36,37

For example, approximately one-fourth of all colonosco-

pies performed in patients under 50 years old are ordered

for patients with symptoms of IBS.38

While this cost analysis focused on diagnostic test-

ing as the main expense, patients with IBS often have

other expenses that are not incorporated; thus, the cost

for a non-rifaximin approach may be underestimated. For

example, patients with IBS often undergo unnecessary

surgical procedures due to their symptoms. These surger-

ies include cholecystectomy, appendectomy, and back

surgery.39 A strategy leading to earlier effective treatment

of IBS could help patients avoid unnecessary surgical

procedures.

Additionally, studies have consistently shown that IBS

is associated with significant indirect costs related to the

Table 3. Sensitivity Analyses

Variable Input (Low), $ Input (High), $ EV (Low), $a EV (High), $a Impact, %b

Rifaximin 627 941 6002 6574 23.93

Colonoscopy 1920 2880 6005 6571 23.50

Gastroenterology visit 216 374 6010 6566 22.61

Abdominal pelvic CT scan 1740 2610 6031 6545 19.30

IBS therapy 10 300 6138 6438 6.56

Endoscopy 656 984 6191 6385 2.74

Celiac screening test 420 630 6226 6350 1.12

Thyroid function test 176 264 6262 6314 0.20

Outpatient visit 74 127 6277 6299 0.03

CT indicates computed tomography; EV, expected value; IBS, irritable bowel syndrome. aEV (low) and EV (high) are the low and high values of the expected costs per treatment arm (ie, rifaximin therapeutic trial arm). The sensitivity analyses used the base case of 3 treat-ments with rifaximin per year. bImpact is an indicator of the variable’s impact on the overall expected cost and was calculated (as a percentage) using the formula: Impact = [EV(High) – EV(Low)]2 / ∑[EV(High) – EV(Low)]2.



high proportion of patients in the workforce.14,24,25 These

patients are prone to high rates of absenteeism (3% to

5% of the work week) and decreased work productiv-

ity (presenteeism; 26% to 31% of the work week).40-42

A cost-benefit analysis of IBS treatment with tegaserod

included absenteeism and presenteeism in the model and

showed a substantial reduction in lost productivity per

patient treated.17 Thus, another potential indirect benefit

for many patients using a rifaximin-treatment-first strat-

egy (which confirms a diagnosis more quickly) may be

an increase in work productivity that occurs sooner than

otherwise expected.

A shift in the treatment paradigm of IBS-D toward a

rifaximin-treatment-first approach will require time and

education, particularly focused on the practicing physi-

cian. Further research confirming the low likelihood of

organic GI disease (eg, colon cancer, Crohn’s disease,

celiac disease) in patients presenting with IBS symptoms

will likely assist in this paradigm shift. While there may

be a concern regarding the potential delay in diagnosis

of organic GI disease, it is unlikely that a delay of up to

3 months would alter the disease prognosis. In fact some

GI diseases are benign and require little treatment, yet

the tendency may be to pursue other costly therapies.

Figure 2. Distribution of Incremental Outcomesa

Figure 3. Tornado Diagrama

0.12

0.10

0.08

0.06

0.04

0.02

0–500 –100 300 700 1100 1500 1900 2300 2700 3100 3500 3900 4300 4700 5100 5500 5900 6300 6700 7100

Incremental Outcome, $

Prob

abili

ty

Probability10/50/90

a This model represents the distribution of incremental outcomes (ie, expected cost [standard of care] minus expected cost [therapeutic trial model]). The mean value of the Monte Carlo simulation was $2398 (95% confidence interval $367-$4974). This simulation represented 100,000 trials.

CT indicates computed tomography; GI, gastroenterology; IBS, irritable bowel syndrome. aImpact of changes in the values of individual variables on the overall expected cost. The decision-analytic model favored the therapeutic trial of rifaximin; hence, the expected values are presented for the rifaximin arm.

$6000 $6200 $6400

Expected Value$6600

Rifaximin: $627-$941

Colonoscopy: $1920-$2880

GI visit: $216-$374

Abdominal pelvic CT scan: $1740-$2610

Other IBS therapy: $10-$300

Endoscopy: $656-$984

Celiac test: $420-$630

Thyroid function test: $176-$264

Follow-up visit: $74-$127



Additionally, there is some risk inherent in performing

unnecessary tests.

As more data become available on the effectiveness

of rifaximin for patients with IBS-D, the adoption of

this treatment-first approach by the medical community

will likely rise. Ad hoc reports by practicing physicians

currently using this approach will also bolster the case

for a therapeutic trial of rifaximin for suspected IBS-D

patients.43

LimitationsThis economic evaluation has some limitations. First,

the efficacy information was drawn from 2 large phase

III clinical trials; and although they are a very robust data

source, resource utilization and cost information was not

available for enrolled patients.13 Also, follow-up data with

respect to the utilization of rifaximin over time are only

beginning to be better understood; additional research is

under way. A recent retrospective study reviewed more

than 500 patients treated with rifaximin, including 71

patients retreated with rifaximin at least 1 time over a

4-year period.26 Some patients had as many as 5 retreat-

ments with no decrease in benefit or duration of effect.

Because rifaximin is a nonabsorbed antibiotic, it has been

postulated that it is unlikely to lead to resistance; this

initial retreatment study lends credence to this hypoth-

esis. The risk for rare adverse events or the potential

for patients to develop pathogens resistant to rifaximin

after long-term therapy cannot be estimated from cur-

rently available data. Likewise, the long-term detriments

of other therapies for IBS (eg, tricyclic antidepressants)

are also unpublished. However, compared with any other

IBS therapy, rifaximin has a superior short-term safety

profile. A recent meta-analysis of treatment options for

IBS-D found that the risk for harm is much greater with

alternatives to rifaximin (1 in 2.3 patients receiving tricy-

clic antidepressants, 1 in 2.6 patients receiving alosetron,

and 1 in 897 patients receiving rifaximin).44

The base case scenario of this model assumed that

all of the possible diagnostic tests would be run when

a patient was referred to a gastroenterologist; thus, this

scenario represented the most extreme case versus the

minimal case of ordering only the celiac test. While phy-

sicians may order only a portion of the diagnostic tests

included in the base case scenario, it is difficult to predict

what proportion of tests would be used on average for

this patient population and it is likely that many patients

do undergo the full battery of tests. It should be noted

that cost assumptions for the diagnostic tests were esti-

mated conservatively, and actual costs may be higher in

many places. Perhaps most important, while there is sig-

nificant evidence to suggest that many of the diagnostic

tests performed on patients presenting with IBS are not

necessary, encouraging a paradigm shift is a difficult and

lengthy process.12

CONCLUSIONSAnalysis of expected cost using a unique decision

tree model of 2 approaches to the initial assessment and

treatment of IBS-D shows that implementation of a rifax-

imin-treatment-first strategy is less costly than the current

standard approach of diagnostic testing followed by treat-

ment. This approach represents an important paradigm

shift for physicians treating patients with GI disorders.

Thus, it will require a lengthy process of personal experi-

ence, peer-to-peer communication, and further confirma-

tory research.

Author Affiliations: From the Gastrointestinal Motility Program and Laboratory, Cedars-Sinai Medical Center (MP), Los Angeles, CA; Division of Gastroenterology, University of Michigan School of Medicine (PS), Ann Arbor MI; Applied Healthcare Resource Management, Inc (CHP, CG, RM), Buffalo, NY.

Funding Source: The study was funded by Salix Pharmaceuticals, Ltd, which markets rifaximin in the United States under license from Alfa Wassermann S.p.A. Medical writing services from Applied Healthcare Resource Management, Inc, were funded by Salix Pharmaceuticals, Ltd.

Author Disclosures: Dr Pimentel reports employment with Cedars-Sinai, which has a licensing agreement with Salix Pharmaceuticals, the funder of this study. He also reports receiving consultancies and grants from Salix Pharmaceuticals, Ltd. Mr Purdy, Dr Gilbert, and Mr Magar all report employment with Applied Healthcare Resource Management, Inc, which received consulting fees from Salix Pharmaceuticals, Ltd to develop this manuscript.

Authorship Information: Concept and design (MP, RM); acquisi-tion of data (CHP); analysis and interpretation of data (MP, CHP); draft-ing of the manuscript (CHP, CG); critical revision of the manuscript for important intellectual content (MP, CG); statistical analysis (CHP); obtain-ing funding (RM); administration, technical, or logistic support (CG); and supervision (RM).

Address correspondence to: Christopher H. Purdy, MA, Applied Healthcare Resource Management, Inc, 701 Ellicott St, Buffalo, NY 14203. E-mail: [email protected].

REFERENCES1. Hungin AP, Chang L, Locke GR, Dennis EH, Barghout V. Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Aliment Pharmacol Ther. 2005;21(11):1365-1375.2. Camilleri M, Andresen V. Current and novel therapeutic options for irritable bowel syndrome management. Dig Liver Dis. 2009;41(12):854-862.3. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders [published correction appears in Gastroenterology. 2006; 131(2):688]. Gastroenterology. 2006;130(5):1480-1491.4. Lehrer JK. Irritable bowel syndrome. http://emedicine.medscape.com/article/ 180389-overview. Accessed December 28, 2010.5. Hungin AP, Whorwell PJ, Tack J, Mearin F. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther. 2003;17(5):643-650.6. Hillilä MT, Färkkilä MA. Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non-selected adult population. Aliment Pharmacol Ther. 2004; 20(3):339-345.



7. Low K, Hwang L, Hua J, Zhu A, Morales W, Pimentel M. A combination of rifaxi-min and neomycin is most effective in treating irritable bowel syndrome patients with methane on lactulose breath test. J Clin Gastroenterol. 2010;44(8):547-550.8. American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, Chey WD, Foxx-Orenstein AE, et al. An evidence-based systematic review on the management of irritable bowel syndrome. Am J Gastroenterol. 2009; 104(suppl 1):S1-S35.9. Dalrymple J, Bullock I. Diagnosis and management of irritable bowel syndrome in adults in primary care: summary of NICE guidance. Br Med J. 2008;336(7643): 556-558.10. Pimentel M, Chatterjee S, Chow EJ, Park S, Kong Y. Neomycin improves constipation-predominant irritable bowel syndrome in a fashion that is dependent on the presence of methane gas: subanalysis of a double-blind randomized con-trolled study. Dig Dis Sci. 2006;51(8):1297-1301.11. Lembo A, Zakko SF, Ferreira NL, et al. Rifaximin for treatment of diarrhea-associated irritable bowel syndrome: short-term treatment leading to long-term sustained response [abstract]. Gastroenterology. 2008;134:A-545. 12. Pimentel M, Park S, Mirocha J, Kane SV, Kong S. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome. Ann Intern Med. 2006;145(8):557-563.13. Pimentel M, Lembo A, Chey WD, et al; TARGET Study Group. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011; 364(1):22-32.14. Cash BD, Schoenfeld P, Chey WD. The utility of diagnostic tests in irritable bowel syndrome patients: a systematic review. Am J Gastroenterol. 2002;97(11): 2812-2819.15. Bracco A, Jönsson B, Ricci JF, Drummond M, Nyhlin H. Economic evaluation of tegaserod vs. placebo in the treatment of patients with irritable bowel syndrome: an analysis of the TENOR study. Value Health. 2007;10(4):238-246.16. McCrone P, Knapp M, Kennedy T, et al. Cost-effectiveness of cognitive behaviour therapy in addition to mebeverine for irritable bowel syndrome. Eur J Gastroenterol Hepatol. 2008;20(4):255-263.17. Smith DG, Barghout V, Kahler KH. Tegaserod treatment for IBS: a model of indirect costs. Am J Manag Care. 2005;11(1)(suppl):S43-S50.18. Ladabaum U. Safety, efficacy and costs of pharmacotherapy for functional gastrointestinal disorders: the case of alosetron and its implications. Aliment Pharmacol Ther. 2003;17(8):1021-1030.19. Creed F, Fernandes L, Guthrie E, et al; North of England IBS Research Group. The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology. 2003;124(2):303-317.20. Martin R, Barron JJ, Zacker C. Irritable bowel syndrome: toward a cost-effective management approach. Am J Manag Care. 2001;7(8)(suppl):S268-S275. 21. Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P. Efficacy of anti-depressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut. 2009;58(3):367-378.22. Rahimi R, Nikfar S, Rezaie A, Abdollahi M. Efficacy of tricyclic antidepressants in irritable bowel syndrome: a meta-analysis. World J Gastroenterol. 2009;15(13): 1548-1553.23. Agency for Healthcare Research and Quality. U.S. Valuation of the EuroQol EQ-5D™ Health States. http://www.ahrq.gov/rice/EQ5Dproj.htm. Published December 2005. Accessed April 14, 2011.24. Cash B, Sullivan S, Barghout V. Total costs of IBS: employer and managed care perspective. Am J Manag Care. 2005;11(1)(suppl):S7-S16.25. Leong SA, Barghout V, Birnbaum HG, et al. The economic consequences of ir-ritable bowel syndrome: a US employer perspective. Arch Intern Med. 2003;163(8): 929-935.

26. Spiegel B, DeRosa VP, Gralnek IM, Wang V, Dulai GS. Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost-effectiveness analy-sis. Gastroenterology 2004;126(7):1721-1732.

27. Wellsphere. Useful resources: at home celiac DNA tests. http://www.wellsphere.com/celiac-disease-article/useful-resources-at-home-celiac-dna-tests/769278. Published August 13, 2009. Accessed April 12, 2011.

28. Cook Medical. Code 44360. 2010 GI Endoscopy Coding and Reimbursement Guide. Effective January 1, 2010–February 28, 2010. http://www.cookmedical.com/esc/content/mmedia/ESC_10USW_RCPT_EN_201001.pdf. Accessed January 3, 2011.

29. New Choice Health website. http://newchoicehealth.com. Accessed January 3, 2011.

30. http://www.hypothyroidism-healing-options.com/thyroid-tests.html. Accessed January 4, 2011.

31. Harvard Pilgrim HealthCare. Massachusetts medical cost data. https://www .harvardpilgrim.org/portal/page?_pageid=253,192924&_dad=portal&_schema= PORTAL. Accessed January 4, 2011.

32. HealthPlans. A Harvard Pilgrim Company. Typical medical costs—Maine (outpatient only). https://www.healthplansinc.com/members/TypicalMedCostsME .aspx. Accessed January 4, 2011.

33. Pimentel M, Morales W, Chua K, et al. Effects of rifaximin treatment and re-treatment in nonconstipated IBS subjects. Dig Dis Sci. 2011;56(7):2067-2072.

34. El-Serag HB, Olden K , Bjorkman D. Health-related quality of life among persons with irritable bowel syndrome: a systematic review. Aliment Pharmacol Ther. 2002; 16(6):1171-1185.

35. Gralnek IM, Hays RD, Kilbourne A, Naliboff B, Mayer EA. The impact of irritable bowel syndrome on health-related quality of life. Gastroenterology. 2000;119(3): 654-660.

36. Talley NJ, Gabriel SE, Harmsen WS, Zinsmeister AR, Evans RW. Medical costs in community subjects with irritable bowel syndrome. Gastroenterology. 1995;109(6): 1736-1741.

37. Longstreth GF, Wilson A, Knight K, et al. Irritable bowel syndrome, health care use, and costs: a US managed care perspective. Am J Gastroenterol. 2003;98(3): 600-607.

38. Lieberman DA, Holub J, Eisen G, et al. Utilization of colonoscopy in the United States: results from a national consortium. Gastrointest Endosc. 2005;62(6): 875-883.

39. Longstreth GF, Yao JF. Irritable bowel syndrome and surgery: a multivariate analysis. Gastroenterology. 2004;126(7):1665-1673.

40. Paré P, Gray J, Lam S, et al. Health-related quality of life, work productivity, and health care resource utilization of subjects with irritable bowel syndrome: baseline results from LOGIC (Longitudinal Outcomes Study of Gastrointestinal Symptoms in Canada), a naturalistic study. Clin Ther. 2006;28(10):1726-1735.

41. Dean BB, Aquilar D, Barghout V, et al. Impairment in work productivity and health-related quality of life in patients with IBS . Am J Manag Care. 2005;11(1)(suppl):S17-S26.

42. Spiegel BMR, Harris L, Lucak S, et al. Predictors of work productivity in irritable bowel syndrome (IBS): results from the PROOF cohort. Gastroenterology. 2008;134(4, suppl 1):A-28.

43. Pimentel M. A New IBS Solution. Los Angeles, CA: Health Point Press; 2005.

44. Pimentel M, Shah E, Kim S, Chong K, Lembo A. Understanding harm in the pharmacotherapy of irritable bowel syndrome with diarrhea. Abstract P1172. http://www.eventscribe.com/2011/acg/PostersPresenters.asp#. Accessed October 28, 2011.

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