Optimizing Diagnostic and Staging Pathways for Suspected Lung Cancer: A Decision Analysis.

BACKGROUND: The optimal diagnostic and staging strategy for patients with suspected lung cancer is not known. RESEARCH QUESTION: What diagnostic and staging strategies are most cost-effective for lung cancer? STUDY DESIGN AND METHODS: A decision model was developed by using a hypothetical patient with a high probability of lung cancer. Sixteen unique permutations of bronchoscopy with fluoroscopy, radial endobronchial ultrasound, electromagnetic navigation, convex endobronchial ultrasound with or without rapid-onsite evaluation (ROSE), CT-guided biopsy (CTBx), and surgery were evaluated. Outcomes included cost, complications, mortality, time to complete the evaluation, rate of undetected N2-3 disease at surgery, incremental cost-complication ratio, and willingness-to-pay thresholds. Sensitivity analyses were performed on primary outcomes. RESULTS: For a peripheral lung lesion and radiographic N0 disease, the best bronchoscopy strategy costs $1,694 more than the best CTBx strategy but resulted in fewer complications (risk difference, 14%). The additional cost of bronchoscopy to avoid one complication from a CTBx strategy was $12,037. The cost and cumulative complications of bronchoscopy strategies increased compared with CTBx strategies for small lesions. The cost and cumulative complications of bronchoscopy strategies decreased compared with CTBx strategies when a bronchus sign was present, but bronchoscopy remained more costly overall. For a central lesion and/or radiographic N1-3 disease, convex endobronchial ultrasound with ROSE followed by lung biopsy with incremental cost-effectiveness ratio, if required, was more cost-effective than any CTBx strategy across all outcomes. Strategies with ROSE were always more cost-effective than those without, irrespective of scenario. Trade-offs also exist between different bronchoscopy strategies, and optimal choices depend on the value placed on individual outcomes and willingness-to-pay. INTERPRETATION: The most cost-effective strategies depend on nodal stage, lesion location, type of peripheral bronchoscopic biopsy, and the use of ROSE. For most clinical scenarios, many strategies can be eliminated, and trade-offs between the remaining competitive strategies can be quantified.

Cost-effectiveness of laparoscopic disease assessment in patients with newly diagnosed advanced ovarian cancer.

OBJECTIVE: To determine if laparoscopy is a cost-effective way to assess disease resectability in patients with newly diagnosed advanced ovarian cancer. METHODS: A cost-effectiveness analysis from a health care payer perspective was performed comparing two strategies: (1) a standard evaluation strategy, where a conventional approach to treatment planning was used to assign patients to either primary cytoreduction (PCS) or neoadjuvant chemotherapy with interval cytoreduction (NACT), and (2) a laparoscopy strategy, where patients considered candidates for PCS would undergo laparoscopy to triage between PCS or NACT based on the laparoscopy-predicted likelihood of complete gross resection. A microsimulation model was developed that included diagnostic work-up, surgical and adjuvant treatment, perioperative complications, and progression-free survival (PFS). Model parameters were derived from the literature and our published data. Effectiveness was defined in quality-adjusted PFS years. Results were tested with deterministic and probabilistic sensitivity analysis (PSA). The willingness-to-pay (WTP) threshold was set at $50,000 per year of quality-adjusted PFS. RESULTS: The laparoscopy strategy led to additional costs (average additional cost $7034) but was also more effective (average 4.1 months of additional quality-adjusted PFS). The incremental cost-effectiveness ratio (ICER) of laparoscopy was $20,376 per additional year of quality-adjusted PFS. The laparoscopy strategy remained cost-effective even as the cost added by laparoscopy increased. The benefit of laparoscopy was influenced by mitigation of serious complications and their associated costs. The laparoscopy strategy was cost-effective across a range of WTP thresholds. CONCLUSIONS: Performing laparoscopy is a cost-effective way to improve primary treatment planning for patients with untreated advanced ovarian cancer.

Cost-utility analysis of treatment options after initial tumor necrosis factor inhibitor therapy discontinuation in patients with rheumatoid arthritis.

BACKGROUND: For patients with rheumatoid arthritis (RA) who discontinued initial treatment with tumor necrosis factor inhibitor (TNFi), 2 approaches are commonly used: cycling to another TNFi or switching to a drug with another mechanism of action. Currently, there is no consensus on which approach to use first. A report from the IBM MarketScan Research administrative claims database showed adalimumab (cycling strategy) and abatacept (switching strategy) were more commonly prescribed after the first TNFi discontinuation. OBJECTIVE: To evaluate the cost-utility of adalimumab versus abatacept in patients with RA whose initial TNFi therapy failed. METHODS: A probabilistic cost-utility microsimulation state-transition model was used. Our target population was commercially insured adults with RA, the time horizon was 10 years, and we used a payer perspective. Patients not responding to adalimumab or abatacept were moved to the next drug in a sequence of 3 and, finally, to conventional synthetic therapy. Incremental cost-utility ratios (2016 USD per quality-adjusted-life-year gained [QALY)] were calculated. Utilities were derived from a formula based on the Health Assessment Questionnaire Disability Index and age-adjusted comorbidity score. RESULTS: Switching to abatacept after the first TNFi showed an incremental cost of just more than $11,300 over 10 years and achieved a QALY benefit of 0.16 compared with adalimumab. The incremental cost-effectiveness ratio was $68,950 per QALY. Scenario analysis produced an incremental cost-effectiveness ratio range of $44,573 per QALY to $148,558 per QALY. Probabilistic sensitivity analysis showed that switching to abatacept after TNFi therapy failure had an 80.6% likelihood of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. CONCLUSIONS: Switching to abatacept is a cost-effective strategy for patients with RA whose discontinue initial therapy with TNFi. DISCLOSURES: Funding for this project was provided by a Rheumatology Research Foundation Investigator Award (principal investigator: Maria A. Lopez-Olivo). Karpes Matusevich's work was supported by a Doctoral Dissertation Research Award from the University of Texas, School of Public Health Office of Research. Lal reports competing interests outside of the submitted work (employed by Optum). Suarez-Almazor reports competing interests outside of the submitted work (consulting fees from Pfizer, AbbVie, Eli Lilly, Agile Therapeutics, Amag Pharmaceuticals, and Gilead). Chan, Swint, and Cantor have nothing to disclose.

Systematic Review of Economic Evaluations of Cycling Versus Swapping Medications in Patients With Rheumatoid Arthritis After Failure to Respond to Tumor Necrosis Factor Inhibitors.

OBJECTIVE: To systematically review the modeling approaches and quality of economic analyses comparing cycling tumor necrosis factor inhibitors (TNFi) to swapping to a therapy with a different mode of action in patients with rheumatoid arthritis whose initial TNFi failed. METHODS: We searched electronic databases, gray literature, and references of included publications until July 2017. Two reviewers independently screened citations. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Data regarding modeling methodology were extracted. RESULTS: We included 7 articles comprising 19 comparisons. Three studies scored ≥16 of 24 on the CHEERS checklist. Most models used a lifetime horizon, took a payer perspective, employed a 6-month cycle length, and measured treatment efficacy in terms of the American College of Rheumatology improvement criteria. We noted possible sources of bias in terms of transparency and study sponsorship. In the cost-utility comparisons, the median incremental cost-effectiveness ratio was US $70,332 per quality-adjusted life-year for swapping versus cycling strategies. Rituximab was more effective and less expensive than TNFi in 7 of 11 comparisons. Abatacept (intravenous) compared to TNFi was less cost-effective than rituximab. Common influential parameters in sensitivity analyses were the rituximab dosing schedule, assumptions regarding disease progression, and the estimation of utilities. CONCLUSION: Differences in the design, key assumptions, and model structure chosen had a major impact on the individual study conclusions. Despite the existence of multiple reporting standards, there continues to be a need for more uniformity in the methodology reported in economic evaluations of cycling versus swapping strategies after TNFi in patients with rheumatoid arthritis.

Cost-Effectiveness Analysis of Hepatitis B Virus Screening and Management in Patients With Hematologic or Solid Malignancies Anticipating Immunosuppressive Cancer Therapy.

PURPOSE: National hepatitis B virus (HBV) screening recommendations for patients with cancer anticipating systemic anticancer therapy range from universal screening to screening based on risk of HBV infection, cancer therapy-specific risk of HBV reactivation, or both. We conducted cost-effectiveness analyses to identify optimal HBV screening strategies. PATIENTS AND METHODS: We constructed decision-analytic models to analyze three strategies (no screening, universal screening, and selective screening based on use of an HBV infection risk tool) for hypothetic cohorts of patients anticipating anticancer therapy at high or lower risk for HBV reactivation. Model parameters were drawn from previously published studies, the SEER-Medicare database, and other online resources. Outcomes included lifetime expected cost, quality-adjusted life expectancy, and incremental cost-effectiveness ratio, measured in US dollars required to gain an additional quality-adjusted life-year (QALY). RESULTS: For patients at high reactivation risk, universal screening dominated (ie, was cheaper and more effective than) the other two strategies. Universal screening was associated with a gain in life expectancy of 0.01 QALY compared with no screening and cost $76.06 less than no screening and $4.34 less than selective screening. For those at lower reactivation risk, universal screening still dominated selective screening; however, the incremental cost-effectiveness ratio of the universal screening strategy compared with no screening was $186,917 per QALY gained. CONCLUSION: Universal HBV screening is cost effective and cheaper for patients receiving anticancer therapy associated with a high reactivation risk. For patients receiving anticancer therapy associated with a lower reactivation risk, universal screening is not cost effective.

Potentially inappropriate medications defined by STOPP criteria in older patients with breast and colorectal cancer.

PURPOSE: Screening for potentially inappropriate medications (PIM) is recommended in older patients with cancer receiving chemotherapy, given the concern for adverse drug reactions, drug-drug interactions and non-adherence. Our objective was to determine the impact of PIM on outcomes in patients with breast and colorectal cancers receiving chemotherapy. METHODS: We used data from the SEER-Medicare database, including patients >/= 66 years old with a diagnosis of Stage II/III breast and colorectal cancer made between 7/1/2007-12/31/2009. We used modified STOPP criteria to define baseline PIM as a dichotomous variable in the 4 months prior to diagnosis. STOPP criteria was used based on its performance as a robust measure of PIM. Outcomes measures included ER visits, hospitalizations, and death within 3 months from the last chemotherapy, and a composite of the three. We used Chi-square or Fisher's exact test to determine associations of PIM with covariates and outcomes, and Cox proportional hazards (PH) model for the time-to-event analysis. RESULTS: Final analysis included 1,595 patients with breast cancer and 1,528 patients with colorectal cancer. Frequency of baseline PIM by STOPP was 31.5% in the breast and 30.9% in the colorectal cohort. In the breast cohort, associations with the composite outcome in the Cox PH model included disease stage, comorbidity, medication number and baseline ER visits/hospitalization. Age, gender, race, comorbidity and baseline ER visits/hospitalization were associated in the colorectal cohort. PIM was not associated with outcomes in either cohort, aside from hospitalization in the breast. CONCLUSIONS: We found no consistent association between pre-chemotherapy PIM defined by STOPP and outcomes.

Cost-effectiveness analysis of smoking cessation interventions using cell phones in a low-income population.

BACKGROUND: The prevalence of cigarette smoking is significantly higher among those living at or below the federal poverty level. Cell phone-based interventions among such populations have the potential to reduce smoking rates and be cost-effective. METHODS: We performed a cost-effectiveness analysis of three smoking cessation interventions: Standard Care (SC) (brief advice to quit, nicotine replacement therapy and self-help written materials), Enhanced Care (EC) (SC plus cell phone-delivered messaging) and Intensive Care (IC) (EC plus cell phone-delivered counselling). Quit rates were obtained from Project ACTION (Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods). We evaluated shorter-term outcomes of cost per quit and long-term outcomes using cost per quality-adjusted life year (QALY). RESULTS: For men, EC cost an additional $541 per quit vs SC; however, IC cost an additional $5232 per quit vs EC. For women, EC was weakly dominated by IC-IC cost an additional $1092 per quit vs SC. Similarly, for men, EC had incremental cost-effectiveness ratio (ICER) of $426 per QALY gained vs SC; however, IC resulted in ICER of $4127 per QALY gained vs EC. For women, EC was weakly dominated; the ICER of IC vs SC was $1251 per QALY gained. The ICER was below maximum acceptable willingness-to-pay threshold of $50 000 per QALY under all alternative modelling assumptions. DISCUSSION: Cell phone interventions for low socioeconomic groups are a cost-effective use of healthcare resources. Intensive Care was the most cost-effective strategy both for men and women. TRIAL REGISTRATION NUMBER: NCT00948129; Results.

Efficacy of Mobile Phone-Delivered Smoking Cessation Interventions for Socioeconomically Disadvantaged Individuals: A Randomized Clinical Trial.

Importance: Limited evidence supports mobile phone-delivered cessation interventions for socioeconomically disadvantaged individuals. Objective: To assess the efficacy of mobile phone-delivered cessation interventions targeted to smokers at neighborhood sites serving racial/ethnic minority and socioeconomically disadvantaged individuals. Design, Setting, and Participants: This group-randomized clinical trial with neighborhood site serving as the sampling unit compared smoking cessation interventions that included (1) nicotine replacement therapy (NRT), (2) NRT plus text messaging, and (3) NRT plus text messaging plus proactive counseling via mobile phone. Recruitment took place at churches, public housing complexes, and community centers located throughout the Houston, Texas, area. A total of 624 current cigarette smokers 18 years or older were enrolled at neighborhood sites from August 13, 2011, through December 12, 2014. Final follow-up was completed on June 12, 2015, and data were analyzed from August 17, 2017, through May 10, 2018, based on intention to treat. Interventions: Nicotine replacement therapy consisted of transdermal nicotine patches; NRT plus text messages, transdermal nicotine patches and individually tailored mobile phone text messages; and NRT plus text plus call, transdermal patches, individually tailored mobile phone text messages, and proactive counseling via mobile phone. Main Outcomes and Measures: The primary outcome was smoking abstinence at 6 months, defined as (1) biochemically verified smoking abstinence (calculated among a subgroup of 377 participants) as determined by saliva cotinine level; and (2) self-reported 30-day abstinence (calculated among all 624 participants). Results: The study sample included 624 current cigarette smokers (50.6% female; mean [SD] age, 45.8 [12.8] years). Among the 377 participants eligible for biochemical verification, 127 self-reported 30-day abstinence and were asked to provide saliva samples. Of these, 98 samples were returned (participants who did not return samples were coded as smoking). Biochemically verified abstinence rates were 12.0% for NRT, 12.0% for NRT plus text, and 25.5% for NRT plus text plus call. Participants in the NRT plus text plus call group were 2.11 (95% CI, 1.00-4.48) times more likely to be biochemically verified as abstinent compared with the NRT group. No differences in biochemically verified abstinence between the NRT plus text group and the NRT group were observed. Similar associations were observed with the self-report cessation outcomes. Conclusions and Relevance: Findings indicate that assignment to an intervention consisting of text messaging alone may not increase cessation rates for socioeconomically disadvantaged smokers. However, text messaging plus proactive counseling may be an efficacious option. Trial Registration: ClinicalTrials.gov identifier: NCT00948129.

Three Lymphadenectomy Strategies in Low-Risk Endometrial Carcinoma: A Cost-Effectiveness Analysis.

OBJECTIVE: To evaluate the cost-utility of three lymphadenectomy strategies in the management of low-risk endometrial carcinoma. METHODS: A decision analysis model compared three lymphadenectomy strategies in women undergoing minimally invasive surgery for low-risk endometrial carcinoma: 1) routine lymphadenectomy in all patients, 2) selective lymphadenectomy based on intraoperative frozen section criteria, and 3) sentinel lymph node mapping. Costs and outcomes were obtained from published literature and Medicare reimbursement rates. Costs categories consisted of hospital, physician, operating room, pathology, and lymphedema treatment. Effectiveness was defined as 3-year disease-specific survival adjusted for the effect of lymphedema (utility=0.8) on quality of life. A cost-utility analysis was performed comparing the different strategies. Multiple deterministic sensitivity analyses were done. RESULTS: In the base-case scenario, routine lymphadenectomy had a cost of $18,041 and an effectiveness of 2.79 quality-adjusted life-years (QALYs). Selective lymphadenectomy had a cost of $17,036 and an effectiveness of 2.81 QALYs, whereas sentinel lymph node mapping had a cost of $16,401 and an effectiveness of 2.87 QALYs. With a difference of $1,005 and 0.02 QALYs, selective lymphadenectomy was both less costly and more effective than routine lymphadenectomy, dominating it. However, with the lowest cost and highest effectiveness, sentinel lymph node mapping dominated the other modalities and was the most cost-effective strategy. These findings were robust to multiple sensitivity analyses varying the rates of lymphedema and lymphadenectomy, surgical approach (open or minimally invasive surgery), lymphedema utility, and costs. For the estimated 40,000 women undergoing surgery for low-risk endometrial carcinoma each year in the United States, the annual cost of routine lymphadenectomy, selective lymphadenectomy, and sentinel lymph node mapping would be $722 million, $681 million, and $656 million, respectively. CONCLUSION: Compared with routine and selective lymphadenectomy, sentinel lymph node mapping had the lowest costs and highest quality-adjusted survival, making it the most cost-effective strategy in the management of low-risk endometrial carcinoma.

Potentially inappropriate medication use in older patients with breast and colorectal cancer.

BACKGROUND: The objective of this study was to determine patient characteristics associated with potentially inappropriate medication (PIM) use and its impact on outcomes for patients with breast or colorectal cancer receiving adjuvant chemotherapy. METHODS: The Surveillance, Epidemiology, and End Results database, linked to Medicare claims, was used. The cohort included patients who were 66 years old or older and were diagnosed with stage II or III breast or colorectal cancer between July 1, 2007, and December 31, 2009. The Drugs to Avoid in the Elderly (DAE) list and the Beers criteria were used to identify PIM use. Univariate/multivariate logistic regression determined the association of baseline PIMs with covariates. Event-free survival (EFS) was defined as the time from chemotherapy initiation to the first emergency room (ER) visit, hospitalization, death, or a composite until 3 months after chemotherapy. Cox proportional hazards modeling determined the association of PIMs with EFS. RESULTS: The analysis included 1595 patients with breast cancer and 1528 patients with colorectal cancer. The baseline PIM frequencies were 22.2% (according to the DAE list) and 27.6% (according to the Beers criteria) in the breast cohort and 15.5% (according to the DAE list) and 24.8% (according to the Beers criteria) in the colorectal cohort. Among patients with breast cancer, 37.5% had at least 1 adverse outcome; associations included the use of ≥5 medications, an advanced stage, higher comorbidity, and prior ER visits/hospitalizations. Baseline PIM use according to the DAE list was associated with an increased risk of death in patients with breast cancer. Among patients with colorectal cancer, 45% had at least 1 adverse outcome, and associations included the use of ≥5 medications, older age, female sex, and higher comorbidity. A time-to-event analysis revealed no association between baseline PIM use and most outcomes. CONCLUSIONS: These findings require further prospective confirmation, but they support a correlation between polypharmacy and adverse outcomes for cancer patients and call into question the association with PIMs. Cancer 2018;124:3000-7. © 2018 American Cancer Society.

Total Lifetime and Cancer-related Costs for Elderly Patients Diagnosed With Anal Cancer in the United States.

OBJECTIVE: To determine the lifetime and phase-specific cost of anal cancer management and the economic burden of anal cancer care in elderly (66 y and older) patients in the United States. PATIENTS AND METHODS: For this study, we used Surveillance Epidemiology and End Results-Medicare linked database (1992 to 2009). We matched newly diagnosed anal cancer patients (by age and sex) to noncancer controls. We estimated survival time from the date of diagnosis until death. Lifetime and average annual cost by stage and age at diagnosis were estimated by combining survival data with Medicare claims. The average lifetime cost, proportion of patients who were elderly, and the number of incident cases were used to estimate the economic burden. RESULTS: The average lifetime cost for patients with anal cancer was US$50,150 (N=2227) (2014 US dollars). The average annual cost in men and women was US$8025 and US$5124, respectively. The overall survival after the diagnosis of cancer was 8.42 years. As the age and stage at diagnosis increased, so did the cost of cancer-related care. The anal cancer-related lifetime economic burden in Medicare patients in the United States was US$112 million. CONCLUSIONS: Although the prevalence of anal cancer among the elderly in the United States is small, its economic burden is considerable.

Clinical and Economic Evaluation of Treatment Strategies for T1N0 Anal Canal Cancer.

OBJECTIVE: A comparative assessment of treatment alternatives for T1N0 anal canal cancer has never been conducted. We compared the outcomes associated with the treatment alternatives-chemoradiotherapy (CRT), radiotherapy (RT), and surgery or ablation techniques (surgery/ablation)-for T1N0 anal canal cancer. MATERIALS AND METHODS: This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) registries linked with Medicare longitudinal data (SEER-Medicare database). Analysis included 190 patients who were treated for T1N0 anal canal cancer using surgery/ablation (n=44), RT (n=50), or CRT (n=96). The outcomes were reported in terms of survival and hazards ratios using Kaplan-Meier and Cox proportional hazards modeling, respectively; lifetime costs; and cost-effectiveness measured in terms of incremental cost-effectiveness ratio, that is, the ratio of the difference in costs between the 2 alternatives to the difference in effectiveness between the same 2 alternatives. RESULTS: There was no significant difference in the survival duration between the treatment groups as predicted by the Kaplan-Meier curves. After adjusting for patient characteristics and propensity score, the hazard ratio of death for the patients who received CRT compared with surgery/ablation was 1.742 (95% confidence interval, 0.793-3.829) and RT was 2.170 (95% confidence interval, 0.923-5.101); however, the relationship did not reach statistical significance. Surgery/ablation resulted in lower lifetime cost than RT or CRT. The incremental cost-effectiveness ratio associated with CRT compared with surgery/ablation was $142,883 per life year gained. CONCLUSIONS: There was no statistically significant difference in survival among the treatment alternatives for T1N0 anal canal cancer. Given that surgery/ablation costs less than RT or CRT and might be cost-effective compared with RT and CRT, it is crucial to explore this finding further in this era of limited health care resources.

Cost-effectiveness Analysis Comparing Conventional, Hypofractionated, and Intraoperative Radiotherapy for Early-Stage Breast Cancer.

Background: Early-stage breast cancer is among the most prevalent and costly malignancies treated in the American health care system. Adjuvant radiotherapy after lumpectomy represents a substantial portion of breast cancer expenditures. The relative value of novel radiotherapeutic approaches such as intraoperative radiotherapy (IORT) and hypofractionated whole breast irradiation (HF-WBI) compared with conventionally fractionated whole breast irradiation (CF-WBI) is unknown. Therefore, we used prospectively collected outcomes from randomized clinical trials (RCTs) to compare the cost-effectiveness of these approaches. Methods: We constructed a decision-analytic model that followed women who were treated with lumpectomy for early-stage breast cancer. Recurrence, mortality, complication rates, and utilities (five-year radiation-associated quality of life scores), were extracted from RCTs. Costs were based on Medicare reimbursement rates. Cost-effectiveness from societal and health care sector perspectives was estimated considering two scenarios-the first assumes that radiation-associated disutility persists five years after treatment, and the second assumes that disutility discontinues. Lifetime outcomes were summarized using incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses evaluated the robustness of the results. Results: HF-WBI dominated CF-WBI (ie, resulted in higher quality-adjusted life-years [QALYs] and lower cost) in all scenarios. HF-WBI also had a greater likelihood of cost-effectiveness compared with IORT; under a societal perspective that assumes that radiation-associated disutility persists, HF-WBI results in an ICER of $17 024 per QALY compared with IORT with a probability of cost-effectiveness of 80% at the $100 000 per QALY willingness-to-pay threshold. If radiation-associated disutility is assumed to discontinue, the ICER is lower ($11 461/QALY), resulting in an even higher (83%) probability of relative cost-effectiveness. The ICER was most sensitive to the probability of metastasis and treatment cost. Conclusions: For women with early-stage breast cancer requiring adjuvant radiotherapy, HF-WBI is cost-effective compared with CF-WBI and IORT.

Management of precancerous anal intraepithelial lesions in human immunodeficiency virus-positive men who have sex with men: Clinical effectiveness and cost-effectiveness.

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at disproportionately high risk for anal cancer. There is no definitive approach to the management of high-grade squamous intraepithelial lesions (HSIL), which are precursors of anal cancer, and evidence suggests that posttreatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves HSIL treatment effectiveness. The objectives of this study were to evaluate the optimal HSIL management strategy with respect to clinical effectiveness and cost-effectiveness and to identify the optimal age for initiating HSIL management. METHODS: A decision analytic model of the natural history of anal carcinoma and HSIL management strategies was constructed for HIV-positive MSM who were 27 years old or older. The model was informed by the Surveillance, Epidemiology, and End Results-Medicare database and published studies. Outcomes included the lifetime cost, life expectancy, quality-adjusted life expectancy, cumulative risk of cancer and cancer-related deaths, and cost-effectiveness from a societal perspective. RESULTS: Active monitoring was the most effective approach in patients 29 years or younger; thereafter, HSIL treatment plus adjuvant qHPV vaccination became most effective. When cost-effectiveness was considered (ie, an incremental cost-effectiveness ratio [ICER] < $100,000/quality-adjusted life-year), do nothing was cost-effective until the age of 38 years, and HSIL treatment plus adjuvant qHPV vaccination was cost-effective beyond the age of 38 years (95% confidence interval, 34-43 years). The ICER decreased as the age at HSIL management increased. Outcomes were sensitive to the rate of HSIL regression or progression and the cost of high-resolution anoscopy and biopsy. CONCLUSIONS: The management of HSIL in HIV-positive MSM who are 38 years old or older with treatment plus adjuvant qHPV vaccination is likely to be cost-effective. The conservative approach of no treatment is likely to be cost-effective in younger patients. Cancer 2017;123:4709-4719. © 2017 American Cancer Society.

Adjuvant HPV vaccination for anal cancer prevention in HIV-positive men who have sex with men: The time is now.

IMPORTANCE: Outcomes of treating high-grade squamous intraepithelial lesions (HSIL), a precursor to anal cancer, remain uncertain. Emerging evidence shows that post HSIL treatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves the effectiveness of treatment. However, no recommendations exist regarding the use of qHPV vaccine as an adjuvant form of therapy. Our objective was to determine whether post-treatment adjuvant vaccination should be adopted in HIV-infected MSM (individuals at highest risk for anal cancer) on the basis of cost-effectiveness determined using existing evidence or whether future research is needed. METHODS: We developed a Markov (state-transition) cohort model to assess the cost-effectiveness of post-treatment adjuvant HPV vaccination of 27years or older HIV-infected MSM. We first estimated cost-effectiveness and then performed value-of-information (VOI) analysis to determine whether future research is required by estimating the expected value of perfect information (EVPI). We also estimated expected value of partial perfect information (EVPPI) to determine what new evidences should have highest priority. RESULTS: With the incremental cost-effectiveness ratio (ICER) of $71,937/QALY, "treatment plus vaccination" was the most cost-effective HSIL management strategy using the willingness-to-pay threshold of 100,000/QALY. We found that population-level EVPI for conducting future clinical research evaluating HSIL management approaches was US$12 million (range $6-$20 million). The EVPPI associated with adjuvant qHPV vaccination efficacy estimated in terms of hazards of decreasing HSIL recurrence was $0 implying that additional data from a future study evaluating efficacy of adjuvant qHPV vaccination will not change our policy conclusion that "treatment plus vaccination" was cost-effective. Both the ICER and EVPI were sensitive to HSIL treatment compliance. CONCLUSION: Post-treatment adjuvant qHPV vaccination in HIV-infected MSM aged 27 or above is likely to be cost-effective. Use of adjuvant qHPV vaccination could be considered as a potential strategy to reduce rising anal cancer burden among these high-risk individuals.

Decision analysis to define the optimal management of athletes with anomalous aortic origin of a coronary artery.

OBJECTIVES: The goal of this study was to use decision analysis to evaluate the impact of varying uncertainties on the outcomes of patients with anomalous aortic origin of a coronary artery. METHODS: Two separate decision analysis models were created: one for anomalous left coronary artery (ALCA) and one for anomalous right coronary artery (ARCA). Three strategies were compared: observation, exercise restriction, and surgery. Probabilities and health utilities were estimated on the basis of existing literature. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Surgery was the optimal management strategy for patients <30 years of age with ALCA. As age increased, observation became an equivalent strategy and eventually surpassed surgery as the treatment of choice. The advantage on life expectancy for surgery over observation ranged from 2.6 ± 1.7 years for a 10-year-old patient to -0.03 ± 0.1 for a 65-year old patient. In patients with ARCA, observation was the optimal strategy for most patients with a life expectancy advantage over surgery of 0.1 ± 0.1 years to 0.2 ± 0.4 years, depending on age. Surgery was the preferred strategy only for patients <25 years of age when the perceived risk of sudden cardiac death was high and the perioperative mortality was low. Exercise restriction was a suboptimal strategy for both ALCA and ARCA in all scenarios. CONCLUSIONS: The optimal management in anomalous aortic origin of a coronary artery depends on multiple factors, including individual patient characteristics. Decision analysis provides a tool to understand how these characteristics affect the outcomes with each management strategy and thus may aid in the decision making process for a particular patient.

Outcomes of contralateral prophylactic mastectomy in relation to familial history: a decision analysis (BRCR-D-16-00033).

BACKGROUND: Family history of breast cancer is associated with an increased risk of contralateral breast cancer (CBC) even in the absence of mutations in the breast cancer susceptibility genes BRCA1/2. We compared quality-adjusted survival after contralateral prophylactic mastectomy (CPM) with surveillance only (no CPM) among women with breast cancer incorporating the degree of family history. METHODS: We created a microsimulation model for women with first-degree, second-degree, and no family history treated for a stage I, II, or III estrogen receptor (ER)-positive or ER-negative breast cancer at the ages of 40, 50, 60, and 70. The model incorporated a 10-year posttreatment period for risk of developing CBC and/or dying of the primary cancer or CBC. For each patient profile, we used 100,000 microsimulation trials to estimate quality-adjusted life expectancy for the clinical strategies CPM and no CPM. RESULTS: CPM showed minimal improvement on quality-adjusted life expectancy among women age 50-60 with no or a unilateral first-degree or second-degree family history (decreasing from 0.31 to -0.06 quality-adjusted life-years (QALYs)) and was unfavorable for most subgroups of women age 70 with stage III breast cancer regardless of degree of family history (range -0.08 to -0.02 QALYs). Sensitivity analysis showed that the highest predicted benefit of CPM assuming 95 % risk reduction in CBC was 0.57 QALYs for a 40-year-old woman with stage I breast cancer who had a first-degree relative with bilateral breast cancer. CONCLUSIONS: Women age 40 with stage I breast cancer and a first-degree relative with bilateral breast cancer have a QALY benefit from CPM similar to that reported for BRCA1/2 mutation carriers. For most subgroups of women, CPM has a minimal to no effect on quality-adjusted life expectancy, irrespective of family history of breast cancer.

Effect of Body Mass Index and Psychosocial Traits on Total Knee Replacement Costs in Patients with Osteoarthritis.

OBJECTIVE: Clinical and psychosocial attributes are associated with clinical outcomes after total knee replacement (TKR) surgery in patients with osteoarthritis (OA), but their relationship with TKR-related costs is less clear. Our objective was to evaluate the effect of clinical and psychosocial attributes on TKR costs. METHODS: We conducted a 6-month prospective cohort study of patients with knee OA who underwent TKR. We examined baseline demographic, clinical [body mass index (BMI) and comorbidities], and psychosocial attributes (social support, locus of control, coping, depression, anxiety, stress, and self-efficacy); baseline and 6-month OA clinical outcomes [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function]; and 6-month direct and indirect TKR-related costs. Multiple regression was performed to identify determinants of TKR-related costs. RESULTS: We included 212 patients; 66% were women, 71% were white, and the mean age was 65.2 years. The mean baseline WOMAC pain score was 55 (SD 19) and WOMAC function score was 54 (SD 20). Mean total TKR-related costs were US$30,831 (SD $9893). Multivariate regression analyses showed that increasing BMI and anxiety levels and decreasing levels of positive social interactions were associated with increased costs. A lower cost scenario with a lower range of normal BMI (19.5), highest positive social interaction, and no anxiety predicted TKR costs to be $22,247. Predicted costs in obese patients (BMI 36) with lowest positive social interaction and highest anxiety were $58,447. CONCLUSION: Increased baseline BMI, anxiety, and poor social support lead to higher TKR-related costs in patients with knee OA. Preoperative interventions targeting these factors may reduce TKR-related costs, and therefore be cost-effective.

Overtreatment and Cost-Effectiveness of the See-and-Treat Strategy for Managing Cervical Precancer.

BACKGROUND: See-and-treat using loop electrosurgical excision procedure (LEEP) has been recommended as an alternative in managing high-grade cervical squamous intraepithelial lesions, but existing literature lacks evidence of the strategy's cost-effectiveness. We evaluated the overtreatment and cost-effectiveness of the see-and-treat strategy compared with usual care. METHODS: We modeled a hypothetical cohort of 40-year-old females who had not been screened for cervical cancer and followed them through their lifetimes using a Markov model. From a U.S. health-system perspective, the analysis was conducted in 2012 dollars and measured effectiveness in quality-adjusted life-years (QALY). We estimated incremental cost-effectiveness ratios (ICER) using a willingness-to-pay threshold of $50,000/QALY. The robustness of the see-and-treat strategy's cost-effectiveness and its overtreatment rates were further examined in various sensitivity analyses. RESULTS: In the base-case, the see-and-treat strategy yielded an ICER of $70,774/QALY compared with usual care. For most scenarios in the deterministic sensitivity analysis, this strategy had ICERs larger than $50,000/QALY, and its cost-effectiveness was sensitive to the disutility of LEEP treatment and biopsy-directed treatment adherence under usual care. Probabilistic sensitivity analysis showed that the see-and-treat strategy had a 50.1% chance to be cost-effective. It had an average overtreatment rate of 7.1% and a 78.8% chance to have its overtreatment rate lower than the 10% threshold. CONCLUSION: The see-and-treat strategy induced an acceptable overtreatment rate. Its cost-effectiveness, compared with usual care, was indiscriminating at the chosen willingness-to-pay threshold but much improved when the threshold increased. IMPACT: The see-and-treat strategy was reasonable for particular settings, that is, those with low treatment adherence. Cancer Epidemiol Biomarkers Prev; 25(5); 807-14. ©2016 AACR.

2013 HIPAA Changes Provide Opportunities and Challenges for Researchers: Perspectives from a Cancer Center.

In 2013, the U.S. Department of Health and Human Services modified the Health Insurance Portability and Accountability Act Privacy Rule to "strengthen privacy and security protections" while "improving workability and effectiveness to increase flexibility for and decrease burden on regulated entities." In this article, we attempt to translate these generalized goals into the real-world implications of these changes. Under the new rules, researchers can obtain participants' permission to use their protected health information for more research activities with a single, upfront authorization (thereby reducing paperwork for participants, researchers, and institutional review boards) while providing potential participants with more information upon which to base their decisions about participation. The combined authorizations can be used in clinical trials and their optional substudies and in stand-alone biospecimen-banking research that includes authorization to permit future research use. We also suggest best practices for taking advantage of the flexibility offered by the new rules while maintaining strong privacy protections for human subjects.