The cost-effectiveness of germline BRCA testing-guided olaparib treatment in metastatic castration resistant prostate cancer.

BACKGROUND: Olaparib targets the DNA repair pathways and has revolutionized the management of metastatic castration resistant prostate cancer (mCRPC). Treatment with the drug should be guided by genetic testing; however, published economic evaluations did not consider olaparib and genetic testing as codependent technologies. This study aims to assess the cost-effectiveness of BRCA germline testing to inform olaparib treatment in mCRPC. METHODS: We conducted a cost-utility analysis of germline BRCA testing-guided olaparib treatment compared to standard care without testing from an Australian health payer perspective. The analysis applied a decision tree to indicate the germline testing or no testing strategy. A Markov multi-state transition approach was used for patients within each strategy. The model had a time horizon of 5 years. Costs and outcomes were discounted at an annual rate of 5 percent. Decision uncertainty was characterized using probabilistic and scenario analyses. RESULTS: Compared to standard care, BRCA testing-guided olaparib treatment was associated with an incremental cost of AU$7,841 and a gain of 0.06 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was AU$143,613 per QALY. The probability of BRCA testing-guided treatment being cost effective at a willingness-to-pay threshold of AU$100,000 per QALY was around 2 percent; however, the likelihood for cost-effectiveness increased to 66 percent if the price of olaparib was reduced by 30 percent. CONCLUSION: This is the first study to evaluate germline genetic testing and olaparib treatment as codependent technologies in mCRPC. Genetic testing-guided olaparib treatment may be cost-effective with significant discounts on olaparib pricing.

A review of the cost-effectiveness of genetic testing for germline variants in familial cancer.

BACKGROUND: Targeted germline testing is recommended for those with or at risk of breast, ovarian, or colorectal cancer. The affordability of genetic sequencing has improved over the past decade, therefore the cost-effectiveness of testing for these cancers is worthy of reassessment. OBJECTIVE: To systematically review economic evaluations on cost-effectiveness of germline testing in breast, ovarian, or colorectal cancer. METHODS: A search of PubMed and Embase databases for cost-effectiveness studies on germline testing in breast, ovarian, or colorectal cancer, published between 1999 and May 2022. Synthesis of methodology, cost-effectiveness, and reporting (CHEERS checklist) was performed. RESULTS: The incremental cost-effectiveness ratios (ICERs; in 2021-adjusted US$) for germline testing versus the standard care option in hereditary breast or ovarian cancer (HBOC) across target settings were as follows: (1) population-wide testing: 344-2.5 million/QALY; (2) women with high-risk: dominant = 78,118/QALY, 8,337-59,708/LYG; (3) existing breast or ovarian cancer: 3,012-72,566/QALY, 39,835/LYG; and (4) metastatic breast cancer: 158,630/QALY. Likewise, ICERs of germline testing for colorectal cancer across settings were: (1) population-wide testing: 132,200/QALY, 1.1 million/LYG; (2) people with high-risk: 32,322-76,750/QALY, dominant = 353/LYG; and (3) patients with existing colorectal cancer: dominant = 54,122/QALY, 98,790-6.3 million/LYG. Key areas of underreporting were the inclusion of a health economic analysis plan (100% of HBOC and colorectal studies), engagement of patients and stakeholders (95.4% of HBOC, 100% of colorectal studies) and measurement of outcomes (18.2% HBOC, 38.9% of colorectal studies). CONCLUSION: Germline testing for HBOC was likely to be cost-effective across most settings, except when used as a co-dependent technology with the PARP inhibitor, olaparib in metastatic breast cancer. In colorectal cancer studies, testing was cost-effective in those with high-risk, but inconclusive in other settings. Cost-effectiveness was sensitive to the prevalence of tested variants, cost of testing, uptake, and benefits of prophylactic measures. Policy advice on germline testing should emphasize the importance of these factors in their recommendations.

Breast, ovarian, prostate, and colorectal cancers are among the top causes of cancer related deaths. A substantial proportion of people with these cancers have inherited mutations. The identification of these gene abnormalities could provide people with opportunities to utilize preventive risk reduction surgeries or undertake frequent routine testing for these cancers. However, genetic testing requires healthcare resources and money. Previous reviews on the cost-effectiveness of genetic testing in familial cancers have concluded that targeted screening i.e., selective assessment of people at high-risk could justify the costs of testing. Our evaluation of economic studies in breast and ovarian cancer, however, suggests that genetic testing is cost-effective across a wide variety of situations starting from the screening of all healthy women above 30 years to the testing of women with existing breast or ovarian cancer. Testing in metastatic breast cancer to inform treatment with Olaparib, a drug known to selectively improve survival in people with genetic mutations, was the sole exception where testing was not cost-effective. Contrary to findings for breast or ovarian cancer, testing for colorectal cancer was cost-effective in people with high-risk i.e., family history but inconclusive in other situations. Evidence on the cost-effectiveness of testing in prostate cancer is lacking and as a result we were not able to provide advice in this cancer group.

Variation in Functional Status After Hip Fracture: Facility and Regional Influence on Mobility and Self-Care.

BACKGROUND: Recent reports show substantial geographic variation in postacute health care spending. Little is known about variation in functional outcomes after postacute rehabilitation for patients with hip fracture. We examined variation in mobility and self-care after hip fracture rehabilitation across inpatient rehabilitation facilities (IRFs), hospital referral regions (HRRs) and states. METHODS: Retrospective cohort study using data from the Centers for Medicare and Medicaid Services (CMS) from 2006 to 2009. Study sample included 149,258 records from patients 66 years and older at 1,166 IRFs located within 292 HRRs and across 50 states. Hip fracture cases were defined by CMS impairment group codes (08.11, 08.12). Hierarchical generalized linear models were used to assess discharge mobility and self-care functional status, adjusting for individual patient characteristics and the random effect of IRFs, HRRs, and states. RESULTS: Variation in discharge mobility status as assessed by the intraclass correlation percentage (ICC%) was 8.8% across IRFs, 4.0% across HRRs, and 1.8% across states. For self-care, the ICCs were 10.2% across IRFs, 4.8% across HRRs, and 2.4% across states. The range of discharge mobility scores (maximum functional status rating to minimum functional status rating) showed a 9.6-point difference for IRFs, 6.5 for regions, and 2.6 for states. Range of discharge self-care scores were 13.1 for IRFs, 6.8 for HRRs, and 3.4 for states. CONCLUSION: Variation in functional status following postacute hip fracture rehabilitation appears to occur primarily at the level of facilities rather than geographic location.

Geographic and facility variation in inpatient stroke rehabilitation: multilevel analysis of functional status.

OBJECTIVE: To examine geographic and facility variation in cognitive and motor functional outcomes after postacute inpatient rehabilitation in patients with stroke. DESIGN: Retrospective cohort design using Centers for Medicare and Medicaid Services (CMS) claims files. Records from 1209 rehabilitation facilities in 298 hospital referral regions (HRRs) were examined. Patient records were analyzed using linear mixed models. Multilevel models were used to calculate the variation in outcomes attributable to facilities and geographic regions. SETTING: Inpatient rehabilitation units and facilities. PARTICIPANTS: Patients (N=145,460) with stroke discharged from inpatient rehabilitation from 2006 through 2009. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Cognitive and motor functional status at discharge measured by items in the CMS Inpatient Rehabilitation Facility-Patient Assessment Instrument. RESULTS: Variation profiles indicated that 19.1% of rehabilitation facilities were significantly below the mean functional status rating (mean ± SD, 81.58±22.30), with 221 facilities (18.3%) above the mean. Total discharge functional status ratings varied by 3.57 points across regions. Across facilities, functional status values varied by 29.2 points, with a 9.1-point difference between the top and bottom deciles. Variation in discharge motor function attributable to HRR was reduced by 82% after controlling for cluster effects at the facility level. CONCLUSIONS: Our findings suggest that variation in motor and cognitive function at discharge after postacute rehabilitation in patients with stroke is accounted for more by facility than geographic location.

Relationship between body mass index and high cystatin levels among US adults.

High cystatin C levels among patients without clinically recognized chronic kidney disease (CKD) may identify patients who are at preclinical stages of CKD. Higher body mass index (BMI) has been found to be associated with increased risk of CKD. However, the association between BMI and high cystatin C levels is not clear. The authors examined participants older than 20 years from the National Health and Nutrition Examination Survey 1999 to 2002 (N=2583, 50.2% women). BMI was categorized as <25 kg/m(2), 25-29.9 kg/m(2), and ≥30 kg/m(2) . Main outcome was high cystatin C (>1 mg/dL) among patients without clinically recognized CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2) or microalbuminuria). Higher BMI was positively associated with high cystatin C, independent of age, sex, race-ethnicity, education, smoking, alcohol intake, cholesterol, and C-reactive protein levels. Compared with patients with BMI <25 kg/m(2) (referent), the multivariable odds ratio (95% confidence interval) of high cystatin C was 2.53 (1.79-3.58) (P trend <.0001 among patients with BMI ≥30 kg/m(2)). The association between BMI and high cystatin C persisted in subgroup analyses by sex, race-ethnicity, and among those without diabetes or hypertension. Among US adults without clinically recognized CKD, higher BMI levels were independently associated with high cystatin C levels.