Lives Saved Through Increasing Adherence to Follow-Up After Abnormal Cervical Cancer Screening Results.

OBJECTIVE: To model the potential number of cancers prevented and life-years saved over a range of adherence rates to cervical cancer screening, surveillance follow-up, and follow-up colposcopy that may result from removing financial barriers to these essential clinical services. METHODS: A previously validated decision-analytic Markov microsimulation model was used to evaluate the increase in adherence to screening, surveillance, and colposcopy after an abnormal cervical cancer screening result. For each incremental increase in adherence, we modeled the number of cervical cancer cases avoided, the stages at which the cancers were detected, the number of cervical cancer deaths avoided, and the number of life-years gained. RESULTS: Compared with current adherence rates, the model estimated that an optimized scenario of perfect screening, surveillance, and colposcopy adherence per 100,000 women currently eligible for screening in the United States was 128 (95% CI, 66-199) fewer cervical cancers detected (23%), 62 (95% CI, 7-120) fewer cervical cancer deaths (20%), and 2,135 (95% CI, 1,363-3,057) more life-years saved. Sensitivity analysis revealed that any increase in adherence led to clinically meaningful health benefits. CONCLUSION: The consequences of not attending routine screening or follow-up after an abnormal cervical cancer screening result are associated with preventable cervical cancer morbidity and premature mortality. Given the potential for the removal of consumer cost sharing to increase the use of necessary follow-up after abnormal screening results and to ultimately reduce cervical cancer morbidity and mortality, public and private payers should remove cost barriers to these essential services.

Temporarily implanted nitinol device versus prostatic urethral lift for minimally invasive surgical treatment of benign prostatic hyperplasia with lower urinary tract symptoms: a matching-adjusted indirect comparison.

INTRODUCTION: To evaluate the safety and efficacy of the temporarily implanted nitinol device (iTind) versus prostatic urethral lift (PUL) for minimally invasive surgical treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia in a matching-adjusted indirect comparison (MAIC). MATERIALS AND METHODS: Seven clinical trials were identified via a systematic literature review. Individual patient data from iTind trials and aggregated data from PUL trials were used in the MAIC. Safety and efficacy outcomes at 12 months post-treatment were compared between the adjusted iTind population and the pooled PUL population. RESULTS: iTind patients were significantly less likely than PUL patients to experience treatment-related adverse events within 3 months (25.0% vs. 79.8%; p < 0.001), including dysuria (17.8% vs. 34.7%; p = 0.001), hematuria (12.0% vs. 25.9%; p = 0.002), and pain (9.5% vs. 18.7%; p = 0.023). Rates of treatment-related adverse events from 3 to 12 months were also significantly lower among iTind than PUL patients (2.6% vs. 24.4%; p < 0.001). iTind and PUL efficacy outcomes were statistically equivalent on changes from baseline to 12 months on the International Prostate Symptom Score, quality of life, Qmax, post-void residual volume, and the Sexual Health Inventory for Men (all p > 0.05). CONCLUSIONS: This MAIC found superior safety and reduced risks of early and later treatment-related adverse events with iTind versus PUL. The 12-month efficacy was equivalent on subjective and objective urinary and sexual health metrics. This study finds that the iTind temporary device provides equivalent efficacy with lower adverse event risks versus the PUL permanent implants for patients with benign prostatic hyperplasia with lower urinary tract symptoms.

Cost-effectiveness of p16/Ki-67 Dual-Stained Cytology Reflex Following Co-testing with hrHPV Genotyping for Cervical Cancer Screening.

The first biomarker-based cervical cancer screening test, p16/Ki-67 dual-stained cytology (DS), has been clinically validated and approved in the United States for triage of women being screened for cervical cancer who test positive for high-risk human papillomavirus (hrHPV). The primary aim of this work is to evaluate the cost-effectiveness of DS triage after co-testing findings of positive non-16/18 HPV types and atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions cytology. A payer-perspective Markov microsimulation model was developed to assess the impact of DS reflex testing. Each comparison simulated 12,250 screening-eligible women through health states defined by hrHPV status and genotype, cervical intraepithelial neoplasia grades 1-3, invasive cervical cancer (ICC) by stage, and cancer-related or non-cancer death. Screening test performance data were from the IMPACT clinical validation trial. Transition probabilities were from population and natural history studies. Costs of baseline medical care, screening visits, tests, procedures, and ICC were included. DS reflex after co-testing was cost-effective with incremental cost-effectiveness ratios per quality-adjusted life-year gained of $15,231 [95% confidence interval (CI), $10,717-$25,400] compared with co-testing with hrHPV pooled primary and genotyped reflex testing, and $23,487 (95% CI, $15,745-$46,175) compared with co-testing with hrHPV genotyping with no reflex test. Screening and medical costs and life-years increased, while ICC costs and risk of ICC death decreased. Incorporating DS reflex into co-testing cervical cancer screening algorithms is projected to be cost-effective. PREVENTION RELEVANCE: The p16/Ki-67 dual-stained cytology (DS) test was recently approved in the United States as a reflex test for cervical cancer screening following positive high-risk human papillomavirus (hrHPV) test results. Adding DS reflex to hrHPV and cervical cytology co-testing strategies in the United States is expected to be cost-effective per life-year or quality-adjusted life-year gained.

Reoperation Rates and Disease Costs for Primary Open-Angle Glaucoma Patients in the United States Treated with Incisional Glaucoma Surgery.

PURPOSE: To evaluate the claims-based 5-year economic and reintervention burden for patients with primary open-angle glaucoma (POAG) after incisional glaucoma surgery in the United States. DESIGN: Retrospective Medicare claims analysis. PARTICIPANTS: One thousand nine hundred forty-five Medicare fee-for-service patients with POAG treated with trabeculectomy, tube shunt, or EX-PRESS shunt procedures from 2010 through 2011. METHODS: Patients with POAG treated with incisional glaucoma surgery (trabeculectomy, tube shunt, or EX-PRESS shunt) from 2010 through 2011 were identified in the Medicare 5% Standard Analytical Files. Ten years of claims data for each patient (2005-2016) were evaluated for prior incisional surgeries and downstream procedures in the treated eye within 5 years of index. Patients' characteristics, downstream procedures, and POAG-related costs were evaluated. Proportions of patients with downstream procedures in the index eye indicating failure of the index surgery, glaucoma reoperations, nonfailure complications, interventions, or cataract surgery were assessed over 5 years of follow-up. MAIN OUTCOME MEASURES: Cumulative rates of index surgery failure and glaucoma reoperations over 5 years after incisional glaucoma surgery. RESULTS: Of 1945 patients, 223 underwent EX-PRESS shunt, 551 underwent tube shunt, and 1171 underwent trabeculectomy at index. Rates of failure, glaucoma reoperations, or nonfailure complications rose over 5 years after index for all patient subgroups. At 1 year, 15.1% of EX-PRESS shunt patients, 11.6% of tube shunt patients, and 8.8% of trabeculectomy patients had experienced failure based on postindex procedures. By 5 years follow-up, these rates were 31.5% of EX-PRESS shunt patients, 27.1% of tube shunt patients, and 23.5% of trabeculectomy patients. Five-year rates of glaucoma reoperations were 18.3%, 14.0%, and 15.1%, respectively. Among tube shunt and trabeculectomy patients with prior incisional surgery, the 5-year failure rates were 32.5% and 32.6%, and reoperations rates were 12.0% and 26.1%, respectively. CONCLUSIONS: More than one-fourth of patients with POAG treated with incisional surgery underwent additional procedures to address index surgery failure within 5 years. Of these, more than half underwent additional incisional glaucoma surgery. These outcomes from clinical practice settings demonstrate that patients with POAG who require incisional surgery continue to need additional safe and effective surgical treatment options to manage their glaucoma.

Cost-effectiveness of adding Endocuff® to standard colonoscopies for interval colorectal cancer screening.

Background and aims: Higher screening colonoscopy adenoma detection rates (ADRs) correlate with reduced risk of interval colorectal cancer (CRC). The Endocuff® device has been shown to improve ADRs compared to standard colonoscopy (SC). This cost-effectiveness analysis compared interval CRC screening using Endocuff®-assisted colonoscopy (EC) vs SC. Methods: A decision-analytic Markov model followed patients through screening, CRC diagnosis, progression, remission, and death. ADRs, CRC progression, and utilities were from literature. CRC incidence, stage distribution, and mortality were from the Surveillance, Epidemiology, and End Results (SEER) and SEER-Medicare linked databases. Screening and annual patient costs were from public databases and literature. Endocuff® device average sales price was applied. Lifetime device and medical costs were evaluated separately for device purchaser, health plan, and accountable care organization (ACO) perspectives. Results: Consistent use of EC instead of SC was expected to reduce lifetime risks of interval CRC and related death by 0.98% and 0.19%, respectively, preventing one case per 102 patients and one death per 526 patients. Survival and quality-of-life (QoL) improved by 0.025 life-years and 0.011 quality-adjusted life-years (QALYs) per patient on average. EC instead of SC led to incremental cost-effectiveness ratios to the device purchaser of $4,421 per life-year gained and $9,843 per QALY gained, and $199 or $87 average cost-savings per patient to the health plan or ACO, respectively. Conclusion: Endocuff® for screening colonoscopies was expected to reduce interval CRC incidence and death, improve QoL, and be cost-effective to the device purchaser and cost-saving to a health plan or ACO.

Multiple Biomarker Testing Tissue Consumption and Completion Rates With Single-gene Tests and Investigational Use of Oncomine Dx Target Test for Advanced Non-Small-cell Lung Cancer: A Single-center Analysis.

INTRODUCTION: First-line targeted therapies have been developed for advanced non-small-cell lung cancer (NSCLC). However, small biopsy samples pose a challenge to testing all relevant biomarkers. The present study characterized clinician-ordered single-gene lung cancer testing and evaluated tissue stewardship and the ability to successfully determine mutation status with single-gene testing or investigational use of the Oncomine Dx Target Test. MATERIALS AND METHODS: Clinician-submitted orders for 3659 single-gene tests (EGFR, ALK, ROS1, BRAF, KRAS, ERBB2, MET, RET, FGFR1) across 1402 samples at a large US-based commercial reference laboratory and 169 investigational Oncomine Dx Target Tests were retrospectively evaluated. The testing success rates and tissue consumption were evaluated by sample type, test type, and number of single-gene tests per sample. RESULTS: The large majority of lung tissue samples submitted for clinical testing were small (70.5% core needle biopsies; 10.0% fine needle aspirations). With single-gene testing, mutation status was successfully reported for ≥ 1 biomarker for 88.4% of the clinical samples. The success rates decreased and tissue consumption increased with testing of additional biomarkers. Investigational Oncomine Dx Target Tests were permitted 1 tissue slide each and demonstrated success rates similar to single-gene testing for ≥ 5 biomarkers on core needle biopsies, ≥ 4 biomarkers on fine needle aspirations, and ≥ 2 biomarkers on surgical resection specimens. CONCLUSION: Tissue stewardship is important to enable successful completion of genetic testing and informed NSCLC treatment decisions. Preliminary assessment of the investigational Oncomine Dx Target Test suggests it could facilitate access to multiple biomarker testing using small tissue samples to support therapy decisions for patients with advanced NSCLC.

Budget Impact of Next-Generation Sequencing for Molecular Assessment of Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Genetic testing for nonsquamous advanced non-small cell lung cancer (aNSCLC) is recommended to guide first-line therapy. Activating mutations can be identified via single-gene testing or next-generation sequencing (NGS). OBJECTIVES: To evaluate the budget impact of NGS instead of single-gene testing for tissue-based molecular assessment of aNSCLC from the US health care payer perspective. METHODS: An annual cohort of newly diagnosed patients with nonsquamous aNSCLC in a hypothetical 1-million-member health care plan was evaluated using a Markov model over 5 years. Epidemiology and testing rates (EGFR, ALK, ROS1, BRAF, MET, HER2, and RET) were from the literature. Treatments were determined by available genetic information. Safety, progression, and survival with targeted therapy or chemotherapy were from randomized clinical trials. Single-gene testing and first-line and maintenance treatment costs were from RED BOOK and Medicare fee schedules; NGS testing, adverse event, and progression costs to payers were from the literature. RESULTS: Three hundred sixteen testing-eligible patients with aNSCLC were expected annually, of whom 179 undergo genetic testing. Of 57 patients expected to have activating mutations, single-gene testing identified 35, whereas NGS identified 54. NGS, instead of single-gene testing, decreased expected testing procedure-related costs to the health plan payer by $24,651. First-line and maintenance treatment costs increased by $842,205, offset by a $385,000 decrease in second-line treatment and palliative care costs. Over 5 years, total budget impact was $432,554 ($0.0072 per member per month). CONCLUSIONS: NGS is expected to identify more patients with activating mutations, thereby better enabling selection for targeted therapy and clinical trial enrollment. The budget impact to US payers is expected to be minimally cost-additive.

Cost-comparison of two trabecular micro-bypass stents versus selective laser trabeculoplasty or medications only for intraocular pressure control for patients with open-angle glaucoma.

AIM: Patients with open-angle glaucoma (OAG) whose intraocular pressure is not adequately controlled by one medication have several treatment options in the US. This analysis evaluated direct costs of unilateral eye treatment with two trabecular micro-bypass stents (two iStents) compared to selective laser trabeculoplasty (SLT) or medications only. MATERIALS AND METHODS: A population-based, annual state-transition, probabilistic, cost-of-care model was used to assess OAG-related costs over 5 years. Patients were modeled to initiate treatment in year zero with two iStents, SLT, or medications only. In years 1-5, patients could remain on initial treatment or move to another treatment option(s), or filtration surgery. Treatment strategy change probabilities were identified by a clinician panel. Direct costs were included for drugs, procedures, and complications. RESULTS: The projected average cumulative cost at 5 years was lower in the two-stent treatment arm ($4,420) compared to the SLT arm ($4,730) or medications-only arm ($6,217). Initial year-zero costs were higher with two iStents ($2,810) than with SLT ($842) or medications only ($996). Average marginal annual costs in years 1-5 were $322 for two iStents, $777 for SLT, and $1,044 for medications only. The cumulative cost differences between two iStents vs SLT or medications only decreased over time, with breakeven by 5 or 3 years post-initiation, respectively. By year 5, cumulative savings with two iStents over SLT or medications only was $309 or $1,797, respectively. LIMITATIONS: This analysis relies on clinical expert panel opinion and would benefit from real-world evidence on use of multiple procedures and treatment switching after two-stent treatment, SLT, or polypharmaceutical initial approaches. CONCLUSIONS: Despite higher costs in year zero, annual costs thereafter were lowest in the two-stent treatment arm. Two-stent treatment may reduce OAG-related health resource use, leading to direct savings, especially over medications only or at longer time horizons.

Comparative economics of a 12-gene assay for predicting risk of recurrence in stage II colon cancer.

BACKGROUND: Prior economic analysis that compared the 12-gene assay to published patterns of care predicted the assay would improve outcomes while lowering medical costs for stage II, T3, mismatch-repair-proficient (MMR-P) colon cancer patients. This study assessed the validity of those findings with real-world adjuvant chemotherapy (aCT) recommendations from the US third-party payer perspective. METHODS: Costs and quality-adjusted life-years (QALYs) were estimated for stage II, T3, MMR-P colon cancer patients using guideline-compliant, state-transition probability estimation methods in a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium provided aCT recommendations before and after knowledge of the 12-gene assay results. Progression and adverse events data with aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2014 Medicare Fee Schedule. Sensitivity analyses evaluated the drivers and robustness of the primary outcomes. RESULTS: After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22 %; fluoropyrimidine monotherapy and FOLFOX recommendations each declined 11 %. Average per-patient drugs, administration, and adverse events costs decreased $US2,339, $US733, and $US3,211, respectively. Average total direct medical costs decreased $US991. Average patient well-being improved by 0.114 QALYs. Savings are expected to persist even if the cost of oxaliplatin drops by >75 % due to generic substitution. CONCLUSIONS: This study provides evidence that real-world changes in aCT recommendations due to the 12-gene assay are likely to reduce direct medical costs and improve well-being for stage II, T3, MMR-P colon cancer patients.

Clinical validity/utility, change in practice patterns, and economic implications of risk stratifiers to predict outcomes for early-stage breast cancer: a systematic review.

BACKGROUND: At least 14 stratifiers exist to assess recurrence risk, chemotherapy response, and overall survival (OS) in women with early-stage breast cancer (ESBC). These stratifiers have not been compared using a recently developed rigorous framework. We performed a systematic review of the literature on clinical validity/utility, change in clinical practice, and economic implications of ESBC stratifiers. METHODS: A systematic literature search was performed using PubMed, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Database of Systematic Reviews, and bibliographies of relevant studies. Data were extracted by two investigators and graded using a previously published framework. The Level-of-Evidence determination for each study was summarized, and the studies that provide evidence on change in clinical practice and economic implications are reported. RESULTS: Fifty-six articles published original evidence addressing the 21-gene recurrence score (n = 31), 70-gene signature (n = 14), Adjuvant! Online (n = 12), 5-antibody immunohistochemistry panel (n = 3), 5-gene expression index (n = 1), and 14-gene signature (n = 1). The 21-gene recurrence score satisfied Level I evidence (the highest level of evidence among five levels) for estimating distant recurrence risk (DRR), OS, and response to adjuvant chemotherapy, and Level II for estimating local recurrence risk. The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS. Adjuvant! Online satisfied Level II evidence for estimating DRR, OS, and chemotherapy response. The 5-gene expression index satisfied Level III evidence for predicting DRR. The 14-gene signature satisfied Level III evidence for predicting DRR and OS. Ten studies reported changes in clinical practice patterns; seven studies reported economic implications. CONCLUSION: The available evidence on the ability of stratifiers to predict risks of recurrence and response to chemotherapy in ESBC is growing. Level-of-Evidence determinations using the newer framework provide a solid scientific foundation for clinical recommendations.