Cost-Effectiveness Analysis of Six Strategies to Treat Recurrent Clostridium difficile Infection.
ABSTRACT: OBJECTIVE:To assess the cost-effectiveness of six treatment strategies for patients diagnosed with recurrent Clostridium difficile infection (CDI) in Canada: 1. oral metronidazole; 2. oral vancomycin; 3.oral fidaxomicin; 4. fecal transplantation by enema; 5. fecal transplantation by nasogastric tube; and 6. fecal transplantation by colonoscopy. PERSPECTIVE:Public insurer for all hospital and physician services. SETTING:Ontario, Canada. METHODS:A decision analytic model was used to model costs and lifetime health effects of each strategy for a typical patient experiencing up to three recurrences, over 18 weeks. Recurrence data and utilities were obtained from published sources. Cost data was obtained from published sources and hospitals in Toronto, Canada. The willingness-to-pay threshold was $50,000/QALY gained. RESULTS:Fecal transplantation by colonoscopy dominated all other strategies in the base case, as it was less costly and more effective than all alternatives. After accounting for uncertainty in all model parameters, there was an 87% probability that fecal transplantation by colonoscopy was the most beneficial strategy. If colonoscopy was not available, fecal transplantation by enema was cost-effective at $1,708 per QALY gained, compared to metronidazole. In addition, fecal transplantation by enema was the preferred strategy if the probability of recurrence following this strategy was below 8.7%. If fecal transplantation by any means was unavailable, fidaxomicin was cost-effective at an additional cost of $25,968 per QALY gained, compared to metronidazole. CONCLUSION:Fecal transplantation by colonoscopy (or enema, if colonoscopy is unavailable) is cost-effective for treating recurrent CDI in Canada. Where fecal transplantation is not available, fidaxomicin is also cost-effective.
Project description:Clostridium difficile infection (CDI) is characterized by high rates of recurrence, resulting in substantial health care costs. The aim of this study was to analyze the cost-effectiveness of treatments for the management of second recurrence of community-onset CDI in France.We developed a decision-analytic simulation model to compare 5 treatments for the management of second recurrence of community-onset CDI: pulsed-tapered vancomycin, fidaxomicin, fecal microbiota transplantation (FMT) via colonoscopy, FMT via duodenal infusion, and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) among the 5 treatments. ICERs were interpreted using a willingness-to-pay threshold of €32,000/QALY. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses.Three strategies were on the efficiency frontier: pulsed-tapered vancomycin, FMT via enema, and FMT via colonoscopy, in order of increasing effectiveness. FMT via duodenal infusion and fidaxomicin were dominated (i.e. less effective and costlier) by FMT via colonoscopy and FMT via enema. FMT via enema compared with pulsed-tapered vancomycin had an ICER of €18,092/QALY. The ICER for FMT via colonoscopy versus FMT via enema was €73,653/QALY. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations showed that FMT via enema was the most cost-effective strategy in 58% of simulations and FMT via colonoscopy was favored in 19% at a willingness-to-pay threshold of €32,000/QALY.FMT via enema is the most cost-effective initial strategy for the management of second recurrence of community-onset CDI at a willingness-to-pay threshold of €32,000/QALY.
Project description:BACKGROUND:In 2018, the Infectious Diseases Society of America (IDSA) published guidelines for diagnosis and treatment of Clostridioides (formerly Clostridium) difficile infection (CDI). However, there is little guidance regarding which treatments are cost-effective. METHODS:We used a Markov model to simulate a cohort of patients presenting with an initial CDI diagnosis. We used the model to estimate the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the recently published 2018 IDSA guidelines. The model includes stratification by the severity of the initial infection, and subsequent likelihood of cure, recurrence, mortality, and outcomes of subsequent recurrences. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS:Use of fidaxomicin for nonsevere initial CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and fecal microbiota transplantation (FMT) for subsequent recurrence (strategy 44) cost an additional $478 for 0.009 QALYs gained per CDI patient, resulting in an ICER of $31 751 per QALY, below the willingness-to-pay threshold of $100 000/QALY. This is the optimal, cost-effective CDI treatment strategy. CONCLUSIONS:Metronidazole is suboptimal for nonsevere CDI as it is less beneficial than alternative strategies. The preferred treatment regimen is fidaxomicin for nonsevere CDI, vancomycin for severe CDI, fidaxomicin for first recurrence, and FMT for subsequent recurrence. The most effective treatments, with highest cure rates, are also cost-effective due to averted mortality, utility loss, and costs of rehospitalization and/or further treatments for recurrent CDI.
Project description:Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI.We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year.At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin.In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.
Project description:BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider. METHODS We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs. RESULTS We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies. CONCLUSIONS The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment. Infect Control Hosp Epidemiol 2018;39:412-424.
Project description:BackgroundClostridioides difficile infection (CDI) is a hospital acquired disease associated with significant morbidity, hospitalisation and mortality. Almost 30% of treated patients experience at least one recurrence after treatment of their first episode. Treatment of recurrent CDI (rCDI) utilises vancomycin or fidaxomicin, however, a newer treatment option is faecal microbial transplantation (FMT) administered by nasogastric tube (NGT) or colonoscopy. It is associated with higher cure and lower recurrence rates than fidaxomicin or vancomycin. The aim of this analysis is to evaluate the cost effectiveness of FMT for rCDI using the latest and best evidence.MethodA cost utility analysis was conducted using a decision model representing the cost per additional Quality Adjusted Life Year (QALY) from a National Health Service (NHS) perspective. A Markov model was constructed to compare FMT NGT and colonoscopy to antibiotic treatment (fidaxomicin or vancomycin). The model was informed by a literature review of clinical evidence, specifically focussing on hospitalised patients with rCDI over 65 years. Both deterministic and probabilistic sensitivity analyses were performed to assess uncertainties around the model inputs and assumptions.FindingsThe base case analysis showed that FMT is a less costly and more effective treatment than either fidaxomicin or vancomycin. FMT colonoscopy was slightly more effective than FMT NGT leading to an additional 0.012 QALYs but more expensive and the incremental cost effectiveness ratio (ICER) was £242,514/QALY. The Probabilistic sensitivity analysis based on 10,000 simulations suggested the probability of FMT NGT being cost effective was almost 78% at £20,000/QALY Willingness–To-Pay (WTP) threshold.InterpretationFMT is both more effective and less costly option than antimicrobial therapy. FMT NGT was the preferred route of administration and is likely to be considered the most cost-effective strategy by decision makers given current acceptable thresholds.
Project description:Colorectal cancer (CRC) screening is underused by minority populations, and patient navigation increases adherence with screening colonoscopy. In this study, the authors estimated the cost-effectiveness of navigation for screening colonoscopy from the perspective of a payer seeking to improve population health.A validated model of CRC screening was informed with inputs from navigation studies in New York City (population: 43% African American, 49% Hispanic, 4% white, 4% other; base-case screening: 40% without navigation, 65% with navigation; navigation costs: $29 per colonoscopy completer, $21 per noncompleter, $3 per non-navigated individual). Two analyses compared: 1) navigation versus no navigation for 1-time screening colonoscopy in unscreened individuals aged ? 50 years; and 2) programs of colonoscopy with versus without navigation versus fecal occult blood testing (FOBT) or fecal immunochemical testing (FIT) for individuals ages 50 to 80 years.In the base case: 1) 1-time navigation gained quality-adjusted life-years (QALYs) and decreased costs; 2) longitudinal navigation cost $9800 per QALY gained versus no navigation, and, assuming comparable uptake rates, it cost $118,700 per QALY gained versus FOBT but was less effective and more costly than FIT. The results were most dependent on screening participation rates and navigation costs: 1) assuming a 5% increase in screening uptake with navigation, and a navigation cost of $150 per completer, 1-time navigation cost $26,400 per QALY gained; and 2) longitudinal navigation with 75% colonoscopy uptake cost <$25,000 per QALY gained versus FIT when FIT uptake was <50%. Probabilistic sensitivity analyses did not alter the conclusions.Navigation for screening colonoscopy appears to be cost-effective, and 1-time navigation may be cost-saving. In emerging health care models that reward outcomes, payers should consider covering the costs of navigation for screening colonoscopy.
Project description:Clostridium difficile infection (CDI) recurs in nearly one-third of patients who develop an initial infection. Recurrent CDI (RCDI) is associated with considerable morbidity, mortality, and cost. Treatment for RCDI has not been not well examined.A systematic review.Sixty-four articles were identified evaluating eight different treatment approaches: metronidazole, vancomycin, fidaxomicin, nitazoxanide, rifampin, immunoglobulins, probiotics, and fecal bacteriotherapy. The meta-analysis found vancomycin to have a similar efficacy to metronidazole, although studies used varying doses and durations of therapy. Fidaxomicin was slightly more efficacious than vancomycin, though the number of studies was small. Good evidence for probiotics was limited. Fecal bacteriotherapy was found to be highly efficacious in a single randomized trial.Metronidazole and vancomycin have good evidence for use in RCDI but heterogeneity in treatment duration and dose precludes robust conclusions. Fidaxomicin may have a role in treatment, but evidence is limited to subgroup analyses. Fecal bacteriotherapy was the most efficacious. Saccharomyces boulardii may have a role as adjunctive treatment.
Project description:BACKGROUND & AIMS:The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this recommendation. METHODS:We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data. RESULTS:Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13-14 CRC cases and 6-7 CRC deaths and gained 27-28 discounted QALYs while saving $163,700-$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50-75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost. CONCLUSIONS:In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons.
Project description:Clostridium difficile infection (CDI) is associated with high management costs, particularly in recurrent cases. Fidaxomicin treatment results in lower recurrence rates than vancomycin and metronidazole, but has higher acquisition costs in Europe and the USA. This systematic literature review summarises economic evaluations (EEs) of fidaxomicin, vancomycin and metronidazole for treatment of CDI.Electronic databases (MEDLINE®, Embase, Cochrane Library) and conference proceedings (ISPOR, ECCMID, ICAAC and IDWeek) were searched for publications reporting EEs of fidaxomicin, vancomycin and/or metronidazole in the treatment of CDI. Reference bibliographies of identified manuscripts were also reviewed. Cost-effectiveness was evaluated according to the overall population of patients with CDI, as well as in subgroups with severe CDI or recurrent CDI, or those at higher risk of recurrence or mortality.Overall, 27 relevant EEs, conducted from the perspective of 12 different countries, were identified. Fidaxomicin was cost-effective versus vancomycin and/or metronidazole in 14 of 24 EEs (58.3%), vancomycin was cost-effective versus fidaxomicin and/or metronidazole in five of 27 EEs (18.5%) and metronidazole was cost-effective versus fidaxomicin and/or vancomycin in two of 13 EEs (15.4%). Fidaxomicin was cost-effective versus vancomycin in most of the EEs evaluating specific patient subgroups. Key cost-effectiveness drivers were cure rate, recurrence rate, time horizon, drug costs and length and cost of hospitalisation.In most EEs, fidaxomicin was demonstrated to be cost-effective versus metronidazole and vancomycin in patients with CDI. These results have relevance to clinical practice, given the high budgetary impact of managing CDI and increasing restrictions on healthcare budgets.This analysis was initiated and funded by Astellas Pharma Inc.
Project description:OBJECTIVES: Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. METHODS: A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20,000/QALY and £30,000/QALY. One-way and probabilistic sensitivity analyses were performed. RESULTS: Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14,515 and £14,344, respectively) and in patients with a first recurrence (£16,535 and £16,926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16,529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30,000/QALY was 60% for severe CDI and 68% in a first recurrence. CONCLUSIONS: Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin.