Transplant physician and surgeon compensation: A sample framework accounting for nonbillable and value-based work.

Work relative value unit (wRVU)-based fee schedules are predominantly used by both the Centers for Medicare & Medicaid Services (CMS) and private payers to determine the payments for physicians' clinical productivity. However, under the Affordable Care Act, CMS is transitioning into a value-based payment structure that rewards patient-oriented outcomes and cost savings. Moreover, in the context of solid organ transplantation, physicians and surgeons conduct many activities that are neither billable nor accounted for in the wRVU models. New compensation models for transplant professionals must (1) justify payments for nonbillable work related to transplant activity/procedures; (2) capture the entire academic, clinical, and relationship-building work effort as part of RVU determination; and (3) move toward a value-based compensation scheme that aligns the incentives for physicians, surgeons, transplant center, payers, and patients. In this review, we provide an example of redesigning RVUs to address these challenges in compensating transplant physicians and surgeons. We define a customized RVU (cRVU) for activities that typically do not generate wRVUs and create an outcome value unit (OVU) measure that incorporates outcomes and cost savings into RVUs to include value-based compensation.

Impact of induction immunosuppression on patient survival in heart transplant recipients treated with tacrolimus and mycophenolic acid in the current allocation era.

BACKGROUND: The practice of induction therapy with either rabbit anti-thymocyte globulin (r-ATG) or interleukin-2 receptor antagonists (IL-2RA) is common among heart transplant recipients. However, its benefits in the setting of contemporary maintenance immunosuppression with tacrolimus/mycophenolic acid (TAC/MPA) are unknown. METHODS: We compared post-transplant mortality among three induction therapy strategies (r-ATG vs IL2-RA vs no induction) in a retrospective cohort analysis of heart transplant recipients maintained on TAC/MPA in the Organ Procurement Transplant Network (OPTN) database between the years 2006 and 2015. We used a multivariable model adjusting for clinically important co-morbidities, and a propensity score analysis using the inverse probability weighted (IPW) method in the final analysis. RESULTS: In multivariable IPW analysis, r-ATG (HR = 1.23; 95% CI = 1.05-1.46, P = 0.01) remained significantly associated with a higher mortality. There was a trend toward having a higher mortality in the IL2-RA (HR = 1.11; 95% CI = 1.00-1.24, P = 0.06) group. Subgroup analyses failed to show a patient survival benefit in using either r-ATG or IL2-RA among any of the subgroups analyzed. CONCLUSION: In this contemporary cohort of heart transplant recipients receiving TAC/MPA, neither r-ATG nor IL2-RA were associated with a survival benefit. On the contrary, adjusted analyses showed a significantly higher mortality in the r-ATG group and a trend toward higher mortality in the IL2-RA group. While caution is needed in interpreting treatment effects in an observational cohort, these data call into question the benefit of induction therapy as a common practice and highlight the need for more studies.

Cost-Effectiveness of Antibody-Based Induction Therapy in Deceased Donor Kidney Transplantation in the United States.

BACKGROUND: Induction therapy in deceased donor kidney transplantation is costly, with wide discrepancy in utilization and a limited evidence base, particularly regarding cost-effectiveness. METHODS: We linked the United States Renal Data System data set to Medicare claims to estimate cumulative costs, graft survival, and incremental cost-effectiveness ratio (ICER - cost per additional year of graft survival) within 3 years of transplantation in 19 450 deceased donor kidney transplantation recipients with Medicare as primary payer from 2000 to 2008. We divided the study cohort into high-risk (age > 60 years, panel-reactive antibody > 20%, African American race, Kidney Donor Profile Index > 50%, cold ischemia time > 24 hours) and low-risk (not having any risk factors, comprising approximately 15% of the cohort). After the elimination of dominated options, we estimated expected ICER among induction categories: no-induction, alemtuzumab, rabbit antithymocyte globulin (r-ATG), and interleukin-2 receptor-antagonist. RESULTS: No-induction was the least effective and most costly option in both risk groups. Depletional antibodies (r-ATG and alemtuzumab) were more cost-effective across all willingness-to-pay thresholds in the low-risk group. For the high-risk group and its subcategories, the ICER was very sensitive to the graft survival; overall both depletional antibodies were more cost-effective, mainly for higher willingness to pay threshold (US $100 000 and US $150 000). Rabbit ATG appears to achieve excellent cost-effectiveness acceptability curves (80% of the recipients) in both risk groups at US $50 000 threshold (except age > 60 years). In addition, only r-ATG was associated with graft survival benefit over no-induction category (hazard ratio, 0.91; 95% confidence interval, 0.84-0.99) in a multivariable Cox regression analysis. CONCLUSIONS: Antibody-based induction appears to offer substantial advantages in both cost and outcome compared with no-induction. Overall, depletional induction (preferably r-ATG) appears to offer the greatest benefits.

SIMULTANEOUS LIVER KIDNEY TRANSPLANTATION IN LIVER TRANSPLANT CANDIDATES WITH RENAL DYSFUNCTION: IMPORTANCE OF CREATININE LEVELS, DIALYSIS, AND ORGAN QUALITY IN SURVIVAL.

BACKGROUND: The survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK transplant survival has not been well described in the literature. METHODS: The Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N=2,700) or SLK (N=1,361) transplantation with moderate renal insufficiency between 2003 and 2013. The study cohort was stratified into four groups based on serum creatinine (Scr< 2 mg/dL versus Scr≥ 2 mg/dL) and dialysis status at listing and at transplant. The patients with end-stage renal disease and requiring acute dialysis more than three months before transplantation were excluded. A propensity score (PS)-matching was performed in each stratified groups to factor out imbalances between the SLK and LTA regarding covariates distribution and to reduce measured confounding. Donor quality was assessed with liver-donor risk index (L-DRI). The primary outcome of interest was post-transplant mortality. RESULTS: On multivariable PS-matched Cox proportional hazard models, SLK led to decrease in post-transplant mortality compared to LTA across all four groups, but only reached statistical significance (HR 0.77; 95% CI, 0.62-0.96) in the recipients not exposed to dialysis and Scr≥ 2 mg/dL at transplant (mortality incidence rate per patient-year 5.7% in SLK vs. 7.6% in LTA, p=0.005). The decrease in mortality was observed among SLK recipients with better quality donors (L-DRI<1.5). CONCLUSIONS: Exposure to pre-transplantation dialysis and donor quality affected overall survival among SLK recipients.

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate.

BACKGROUND AND OBJECTIVES: IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. RESULTS: Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99). CONCLUSIONS: In DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols.

Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance.

BACKGROUND AND OBJECTIVES: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. RESULTS: Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. CONCLUSIONS: Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

Predicting invasive breast cancer versus DCIS in different age groups.

BACKGROUND: Increasing focus on potentially unnecessary diagnosis and treatment of certain breast cancers prompted our investigation of whether clinical and mammographic features predictive of invasive breast cancer versus ductal carcinoma in situ (DCIS) differ by age. METHODS: We analyzed 1,475 malignant breast biopsies, 1,063 invasive and 412 DCIS, from 35,871 prospectively collected consecutive diagnostic mammograms interpreted at University of California, San Francisco between 1/6/1997 and 6/29/2007. We constructed three logistic regression models to predict the probability of invasive cancer versus DCIS for the following groups: women ≥ 65 (older group), women 50-64 (middle age group), and women < 50 (younger group). We identified significant predictors and measured the performance in all models using area under the receiver operating characteristic curve (AUC). RESULTS: The models for older and the middle age groups performed significantly better than the model for younger group (AUC = 0.848 vs, 0.778; p = 0.049 and AUC = 0.851 vs, 0.778; p = 0.022, respectively). Palpability and principal mammographic finding were significant predictors in distinguishing invasive from DCIS in all age groups. Family history of breast cancer, mass shape and mass margins were significant positive predictors of invasive cancer in the older group whereas calcification distribution was a negative predictor of invasive cancer (i.e. predicted DCIS). In the middle age group--mass margins, and in the younger group--mass size were positive predictors of invasive cancer. CONCLUSIONS: Clinical and mammographic finding features predict invasive breast cancer versus DCIS better in older women than younger women. Specific predictive variables differ based on age.

A comprehensive methodology for determining the most informative mammographic features.

This study aims to determine the most informative mammographic features for breast cancer diagnosis using mutual information (MI) analysis. Our Health Insurance Portability and Accountability Act-approved database consists of 44,397 consecutive structured mammography reports for 20,375 patients collected from 2005 to 2008. The reports include demographic risk factors (age, family and personal history of breast cancer, and use of hormone therapy) and mammographic features from the Breast Imaging Reporting and Data System lexicon. We calculated MI using Shannon's entropy measure for each feature with respect to the outcome (benign/malignant using a cancer registry match as reference standard). In order to evaluate the validity of the MI rankings of features, we trained and tested naïve Bayes classifiers on the feature with tenfold cross-validation, and measured the predictive ability using area under the ROC curve (AUC). We used a bootstrapping approach to assess the distributional properties of our estimates, and the DeLong method to compare AUC. Based on MI, we found that mass margins and mass shape were the most informative features for breast cancer diagnosis. Calcification morphology, mass density, and calcification distribution provided predictive information for distinguishing benign and malignant breast findings. Breast composition, associated findings, and special cases provided little information in this task. We also found that the rankings of mammographic features with MI and AUC were generally consistent. MI analysis provides a framework to determine the value of different mammographic features in the pursuit of optimal (i.e., accurate and efficient) breast cancer diagnosis.

Cost-effectiveness of adjuvant FOLFOX and 5FU/LV chemotherapy for patients with stage II colon cancer.

PURPOSE: We evaluated the cost-effectiveness of adjuvant chemotherapy using 5-fluorouracil, leucovorin (5FU/LV), and oxaliplatin (FOLFOX) compared with 5FU/LV alone and 5FU/LV compared with observation alone for patients who had resected stage II colon cancer. METHODS: We developed 2 Markov models to represent the adjuvant chemotherapy and follow-up periods and a single Markov model to represent the observation group. We used calibration to estimate the transition probabilities among different toxicity levels. The base case considered 60-year-old patients who had undergone an uncomplicated hemicolectomy for stage II colon cancer and were medically fit to receive 6 months of adjuvant chemotherapy. We measured health outcomes in quality-adjusted life-years (QALYs) and estimated costs using 2007 US dollars. RESULTS: In the base case, adjuvant chemotherapy of the FOLFOX regimen had an incremental cost-effectiveness ratio (ICER) of $54,359/QALY compared with the 5FU/LV regimen, and the 5FU/LV regimen had an ICER of $14,584/QALY compared with the observation group from the third-party payer perspective. The ICER values were most sensitive to 5-year relapse probability, cost of adjuvant chemotherapy, and the discount rate for the FOLFOX arm, whereas the ICER value of 5FU/LV was most sensitive to the 5-year relapse probability, 5-year survival probability, and the relapse cost. The probabilistic sensitivity analysis indicates that the ICER of 5FU/LV is less than $50,000/QALY with a probability of 99.62%, and the ICER of FOLFOX as compared with 5FU/LV is less than $50,000/QALY and $100,000/QALY with a probability of 44.48% and 97.24%, respectively. CONCLUSION: Although adjuvant chemotherapy with 5FU/LV is cost-effective at all ages for patients who have undergone an uncomplicated hemicolectomy for stage II colon cancer, FOLFOX is not likely to be cost-effective as compared with 5FU/LV.

The Effect of Budgetary Restrictions on Breast Cancer Diagnostic Decisions.

We develop a finite-horizon discrete-time constrained Markov decision process (MDP) to model diagnostic decisions after mammography where we maximize the total expected quality-adjusted life years (QALYs) of a patient under resource constraints. We use clinical data to estimate the parameters of the MDP model and solve it as a mixed-integer program. By repeating optimization for a sequence of budget levels, we calculate incremental cost-effectiveness ratios attributable to consecutive levels of funding and compare actual clinical practice with optimal decisions. We prove that the optimal value function is concave in the allocated budget. Comparing to actual clinical practice, using optimal thresholds for decision making may result in approximately 22% cost savings without sacrificing QALYs. Our analysis indicates short-term follow-ups are the immediate target for elimination when budget becomes a concern. Policy change is more drastic in the older age group with the increasing budget, yet the gains in total expected QALYs related to larger budgets are predominantly seen in younger women along with modest gains for older women.