Cost-effectiveness analysis of CYP3A5 genotype-guided tacrolimus dosing in solid organ transplantation using real-world data.

The objective of this study was to estimate the cost-effectiveness of CYP3A5 genotype-guided tacrolimus dosing in kidney, liver, heart, and lung transplant recipients relative to standard of care (SOC) tacrolimus dosing, from a US healthcare payer perspective. We developed decision-tree models to compare economic and clinical outcomes between CYP3A5 genotype-guided and SOC tacrolimus therapy in the first six months post-transplant. We derived inputs for CYP3A5 phenotype frequencies and physician use of genotype test results to inform clinical care from literature; tacrolimus exposure [high vs low tacrolimus time in therapeutic range using the Rosendaal algorithm (TAC TTR-Rosendaal)] and outcomes (incidences of acute tacrolimus nephrotoxicity, acute cellular rejection, and death) from real-world data; and costs from the Medicare Fee Schedule and literature. We calculated cost per avoided event and performed sensitivity analyses to evaluate the robustness of the results to changes in inputs. Incremental costs per avoided event for CYP3A5 genotype-guided vs SOC tacrolimus dosing were $176,667 for kidney recipients, $364,000 for liver recipients, $12,982 for heart recipients, and $93,333 for lung recipients. The likelihood of CYP3A5 genotype-guided tacrolimus dosing leading to cost-savings was 19.8% in kidney, 32.3% in liver, 51.8% in heart, and 54.1% in lung transplant recipients. Physician use of genotype results to guide clinical care and the proportion of patients with a high TAC TTR-Rosendaal were key parameters driving the cost-effectiveness of CYP3A5 genotype-guided tacrolimus therapy. Relative to SOC, CYP3A5 genotype-guided tacrolimus dosing resulted in a slightly greater benefit at a higher cost. Further economic evaluations examining intermediary outcomes (e.g., dose modifications) are needed, particularly in populations with higher frequencies of CYP3A5 expressers.

Cost-effectiveness of Intestinal Transplantation Compared to Parenteral Nutrition in Adults.

BACKGROUND: Intestinal transplantation (ITx) is the most expensive abdominal organ transplant. Detailed studies about exact costs and cost-effectiveness compared to home parenteral nutrition (HPN) therapy in chronic intestinal failure are lacking. The aim is to provide an in-depth analysis of ITx costs and evaluate cost-effectiveness compared to HPN. METHODS: To calculate costs before and after ITx, costs were analyzed in 12 adult patients. To calculate the costs of patients with uncomplicated chronic intestinal failure, 28 adults, stable HPN patients were studied. Total costs including surgery, admissions, diagnostics, HPN therapy, medication, and ambulatory care were included. Median (range) costs are given. RESULTS: Costs before ITx were €69 160 (€60 682-90 891) in year 2, and €104 146 (€83 854-186 412) in year 1. After ITx, costs were €172 133 (€122 483-351 407) in the 1st year, €40 619 (€3905-113 154) in the 2nd year, and dropped to €15 743 (€4408-138 906) in the 3rd year. In stable HPN patients, the costs were €83 402 (€35 364-169 146) in the 1st year, €70 945 (€31 955-117 913) in the 2nd year, and stabilized to €60 242 (€29 161-238 136) in the 3rd year. CONCLUSIONS: ITx, although initially very expensive, is cost-effective compared to HPN in adults by year 4, and cost-saving by year 5.

Economic considerations in abdominal transplantation.

Care for end-stage organ failure through transplant is one of the landmark accomplishments of the modern medicine. At the same time, organ transplant is a resource-intensive service that has been under increasing scrutiny in this era of cost containment. A detailed understanding of the economic implications of organ quality, recipient characteristics, and allocation policy is vital for the transplant professionals. Prior studies of kidney transplant economics demonstrate significant cost savings achieved by eliminating the need for long-term dialysis. However, transplant providers are experiencing higher financial costs because of changes in recipient characteristics. Liver transplantation economics are also more challenging because of organ allocation based on the severity of illness. Furthermore, the broader use of marginal organs has been demonstrated to increase costs. Novel strategies are vital to reduce the financial burden faced by the centers that perform transplantations on elevated risk patients and utilize lower quality organs.

Cost-Effectiveness Analysis of Screening for Persistent Hepatitis E Virus Infection in Solid Organ Transplant Patients in the United Kingdom: A Model-Based Economic Evaluation.

BACKGROUND: Despite potentially severe and fatal outcomes, recent studies of solid organ transplant (SOT) recipients in Europe suggest that hepatitis E virus (HEV) infection is underdiagnosed, with a prevalence of active infection of up to 4.4%. OBJECTIVES: To determine the cost-effectiveness of introducing routine screening for HEV infection in SOT recipients in the UK. METHODS: A Markov cohort model was developed to evaluate the cost-utility of 4 HEV screening options over the lifetime of 1000 SOT recipients. The current baseline of nonsystematic testing was compared with annual screening of all patients by polymerase chain reaction (PCR; strategy A) or HEV-antigen (HEV-Ag) detection (strategy B) and selective screening of patients who have a raised alanine aminotransferase (ALT) value by PCR (strategy C) or HEV-Ag (strategy D). The primary outcome was the incremental cost per quality-adjusted life-year (QALY). We adopted the National Health Service (NHS) perspective and discounted future costs and benefits at 3.5%. RESULTS: At a willingness-to-pay of £20 000/QALY gained, systematic screening of SOT patients by any method (strategy A-D) had a high probability (77.9%) of being cost-effective. Among screening strategies, strategy D is optimal and expected to be cost-saving to the NHS; if only PCR testing strategies are considered, then strategy C becomes cost-effective (£660/QALY). These findings were robust against a wide range of sensitivity and scenario analyses. CONCLUSIONS: Our model showed that routine screening for HEV in SOT patients is very likely to be cost-effective in the UK, particularly in patients presenting with an abnormal alanine aminotransferase.

Evolving ethical issues with advances in uterus transplantation.

While uterus transplantation was once considered only a theoretical possibility for patients with uterine factor infertility, researchers have now developed methods of transplantation that have led to successful pregnancies with multiple children born to date. Because of the unique and significant nature of this type of research, it has been undertaken with collaboration not only with scientists and physicians but also with bioethicists, who paved the initial path for research of uterus transplantation to take place. As the science of uterus transplantation continues to advance, so too must the public dialogue among obstetrician/gynecologists, transplant surgeons, bioethicists, and other key stakeholders in defining the continued direction of research in addition to planning for the clinical implementation of uterus transplantation as a therapeutic option. Given the rapid advances in this field, the time has come to revisit the fundamental questions raised at the inception of uterus transplantation and, looking forward, determine the future of this approach given emerging data on the procedure's impact on individuals, families, and society.

Pure Altruistic Gift and the Ethics of Transplant Medicine.

The article argues that altruistic giving based on anonymity, which is expected to promote social solidarity and block trade in human body parts, is conceptually defective and practically unproductive. It needs to be replaced by a more adequate notion which responds to the human practices of giving and receiving. The argument starts with identification of the main characteristics of the anonymous altruistic donation: social separation of the organ donor (or donor family) from the recipient, their mutual replaceability, non-obligatoriness of donation, and non-obligatoriness of reciprocation on the recipient's part. Since these characteristics are also central to typical market relations, anonymous altruistic donation not only cannot promote solidarity but may encourage proposals for (regulated) markets of transplantable organs. Thus, transplant ethics needs to be reframed. It needs to be rooted in, rather than promote, the practices of giving and receiving known to human societies. As the basis for such reframing, the idea of sharing in another's misfortune is proposed. It relies on the human practices of giving and receiving and, with appropriate regulatory safeguards, can provide a better conceptual basis for blocking commercial exchanges of human body parts.

Best practices to optimize utilization of the National Living Donor Assistance Center for the financial assistance of living organ donors.

Living organ donors face direct costs when donating an organ, including transportation, lodging, meals, and lost wages. For those most in need, the National Living Donor Assistance Center (NLDAC) provides reimbursement to defray travel and subsistence costs associated with living donor evaluation, surgery, and follow-up. While this program currently supports 9% of all US living donors, there is tremendous variability in its utilization across US transplant centers, which may limit patient access to living donor transplantation. Based on feedback from the transplant community, NLDAC convened a Best Practices Workshop on August 2, 2018, in Arlington, VA, to identify strategies to optimize transplant program utilization of this valuable resource. Attendees included team members from transplant centers that are high NLDAC users; the NLDAC program team; and Advisory Group members. After a robust review of NLDAC data and engagement in group discussions, the workgroup identified concrete best practices for administrative and transplant center leadership involvement; for individuals filing NLDAC applications at transplant centers; and to improve patient education about potential financial barriers to living organ donation. Multiple opportunities were identified for intervention to increase transplant programs' NLDAC utilization and reduce financial burdens inhibiting expansion of living donor transplantation in the United States.

Stakeholder perspectives of the clinical utility of pharmacogenomic testing in solid organ transplantation.

Aims: To assess stakeholder perspectives regarding the clinical utility of pharmacogenomic (PGx) testing following kidney, liver, and heart transplantation. Methods: We conducted individual semi-structured interviews and focus groups with kidney, liver, and heart transplantation patients and providers. We analyzed the qualitative data to identify salient themes. Results: The study enrolled 36 patients and 24 providers. Patients lacked an understanding about PGx, but expressed interest in PGx testing. Providers expressed willingness to use PGx testing, but reported barriers to implementation, such as lack of knowledge, lack of evidence demonstrating clinical utility, and patient healthcare burden. Conclusion: Patient and provider educational efforts, including foundational knowledge, clinical evidence, and applications to patient care beyond just immunosuppression, may be useful to facilitate the use of PGx testing in transplant medicine.

Survey for the Opinion of Medical Students and Medical Staff on a Financial Incentive System for Deceased Organ Donation in an Asian Country.

BACKGROUND: Financial incentives for deceased organ donation are associated with many controversial ethical issues. This study examines the perspectives of medical students and staff members on financial incentives for the families of brain-dead organ donors. METHODOLOGY: A structured survey form was used between December 7, 2017 and January 28, 2018 to elicit opinions on financial incentives for the families of brain-dead organ donors. Forty-three medical staff members and 81 medical students participated in the survey voluntarily. The opinions on the financial incentive system and the relationship between willingness to give information about organ donation to families and a financial incentive system were assessed. RESULTS: The majority of the participants (81.4%) had positive thoughts on organ donation. More than half of the participants (60.5%) thought that the financial incentive system did not erode the ethical purity of organ donation. As charge doctors, most respondents (84.6%) were willing to give information about organ donation to family members in the presence of financial incentives. However, the percentage decreased significantly to 60.5% when financial incentive was no longer factored into consideration (P < .001). LIMITATION: The study population is small, and the participants are not representative of the general population. CONCLUSION: The opinions of medical students and medical staff on financial incentives for deceased organ donation were generally positive. Financial incentives proved to be a potential influencing factor as an option of organ donation to be given to families.

What constitutes a reasonable compensation for non-commercial oocyte donors: an analogy with living organ donation and medical research participation.

There is a growing consensus that the offer of a reasonable compensation for oocyte donation for reproductive treatment is acceptable if it does not compromise voluntary and altruistically motivated donation. However, how to translate this 'reasonable compensation' in practice remains unclear as compensation rates offered to oocyte donors between different European Union countries vary significantly. Clinics involved in oocyte donation, as well as those in other medical contexts, might be encouraged in calculating a more consistent and transparent compensation for donors if the elements that constitute a reasonable compensation are explicated. In doing so, lessons can be learnt from living organ donation and medical research participation. Practices in which the elements of a reasonable compensation for the individuals involved have already been more defined in the literature. By means of analogical reasoning, we will outline the different components of a reasonable compensation and subsequently apply these to the context of oocyte donation. We will argue that oocyte donors should first of all be reasonably reimbursed direct expenses related to the donation, without standard remuneration of lost wages. Second, donating oocytes requests a serious time investment, therefore donors are entitled to suitable compensation for their time spent and efforts made. Finally, we will explain that a reasonable compensation consisting of these two components allows for altruism to remain the key value of oocyte donation for reproductive treatment. However, if we acknowledge that donors' motives are more complex and often include reasons from self-interest, the reasonable compensation may be complemented with modest (non)monetary benefits.

Will more organs save more lives? Cost-effectiveness and the ethics of expanding organ procurement.

The assumption that procuring more organs will save more lives has inspired increasingly forceful calls to increase organ procurement. This project, in contrast, directly questions the premise that more organ transplantation means more lives saved. Its argument begins with the fact that resources are limited and medical procedures have opportunity costs. Because many other lifesaving interventions are more cost-effective than transplantation and compete with transplantation for a limited budget, spending on organ transplantation consumes resources that could have been used to save a greater number of other lives. This argument has not yet been advanced in debates over expanded procurement and could buttress existing concerns about expanded procurement. To support this argument, I review existing empirical data on the cost-effectiveness of transplantation and compare them to data on interventions for other illnesses. These data should motivate utilitarians and others whose primary goal is maximizing population-wide health benefits to doubt the merits of expanding organ procurement. I then consider two major objections: one makes the case that transplant candidates have a special claim to medical resources, and the other challenges the use of cost-effectiveness to set priorities. I argue that there is no reason to conclude that transplant candidates' medical interests should receive special priority, and that giving some consideration to cost-effectiveness in priority setting requires neither sweeping changes to overall health priorities nor the adoption of any specific, controversial metric for assessing cost-effectiveness. Before searching for more organs, we should first ensure the provision of cost-effective care.

Secular Trends in the Cost of Immunosuppressants after Solid Organ Transplantation in the United States.

BACKGROUND AND OBJECTIVES: Immunosuppressive medications are critical for maintenance of graft function in transplant recipients but can represent a substantial financial burden to patients and their insurance carriers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To determine whether availability of generic immunosuppressive medications starting in 2009 may have alleviated some of that burden, we used Medicare Part D prescription drug events between 2008 and 2013 to estimate the average annualized per-patient payments made by patients and Medicare in a large national sample of kidney, liver, and heart transplant recipients. Repeated measures linear regression was used to determine changes in payments over the study period. RESULTS: Medicare Part D payments for two commonly used immunosuppressive medications, tacrolimus and mycophenolic acid (including mycophenolate mofetil and mycophenolate sodium), decreased overall by 48%-67% across organs and drugs from 2008 to 2013, reflecting decreasing payments for brand and generic tacrolimus (21%-54%), and generic mycophenolate (72%-74%). Low-income subsidy payments, which are additional payments made under Medicare Part D, also decreased during the study period. Out-of-pocket payments by patients who did not receive the low-income subsidy decreased by more than those who did receive the low-income subsidy (63%-79% versus 24%-44%). CONCLUSIONS: The decline in payments by Medicare Part D and by transplant recipients for tacrolimus and mycophenolate between 2008 and 2013 suggests that the introduction of generic immunosuppressants during this period has resulted in substantial cost savings to Medicare and to patients, largely reflecting the transition from brand to generic products.

Expanding analytic possibilities in pediatric solid organ transplantation through linkage of administrative and clinical registry databases.

Database linkage is a common strategy to expand analytic possibilities. Our group recently completed a linkage between the SRTR and PHIS databases for pediatric heart transplant recipients. The aim of this project was to expand the linkage between SRTR and PHIS to include liver, kidney, lung, heart-lung, and small bowel transplants. All patients (<21 years) who underwent liver, kidney, lung, heart-lung, or small bowel transplant were identified from the PHIS database using APR-DRG codes (2002-2018). Linkage was performed in a stepwise approach using indirect identifiers. Hospital costs were estimated based on hospital charges and cost-to-charge ratios, inflated to 2018 dollars and described by transplant type. A total of 14 061 patients overlapped between databases. Of these, 13 388 (95.2%) were uniquely linked. Linkage success ranged from 92.6% to 97.8% by organ system. A total of 12 940 (92%) patients had complete cost data. Hospitalization costs were greatest for patients undergoing small bowel transplantation with a median cost of $734 454 (IQR $336 174 - $1 504 167), followed by heart $565 386 (IQR $352 813 - $999 216), heart-lung $471 573 (IQR $328 523 - 992 438), lung $303 536 (IQR $215 383 - $612 749), liver $200 448 (IQR $130 880 - $357 897), and kidney transplant $94 796 (IQR $73 157 -$131 040). We report a robust linkage between the SRTR and PHIS databases, providing an invaluable tool to assess resource utilization in solid organ transplant recipients. Our analysis provides contemporary cost data for pediatric solid organ transplantation from the largest US sample reported to date. It also provides a platform for expanded analyses in the pediatric transplant population.

Financial compensation for organ donors.

PURPOSE OF REVIEW: With an increasing demand for donor organs, strategies to increase the number of available donor organs have become more focused. Compensating donors for donation is one strategy proposed to increase the availability of organs for transplant. This has been implemented in several systems internationally, but debate continues in the United States with respect to appropriate strategies. The National Organ Transplant Act (NOTA) currently prohibits the transfer of any human organ 'for valuable consideration' for transplantation, but allows for the removal of financial disincentives. RECENT FINDINGS: Several proposals currently exist for compensating patients for living donation. Recent data have focused on studying and creating mechanisms for reimbursement of costs incurred as part of the donation process, which is related to the removal of disincentives to living donation. Others have advocated for the provision of actual incentives to patients for the act of donating, in an attempt to further expand living donation. The current debate focuses on what measures can reasonably be taken to increase donation, and whether additional incentives will encourage more donation or reduce the motivation for altruistic donation. SUMMARY: Currently, the transplant community broadly supports the removal of disincentives for living donors, including reimbursement of expenses for travel, housing and lost wages incurred during evaluation, surgery and after care. Others have advocated for financial incentives to further increase the number of donor organs available for transplant. Although the removal of disincentives is currently allowed under the existing legal structure of NOTA, providing financial incentives for living donation would require further evaluation of the economics, law, ethics and public readiness for a significant policy shift.

The effects of a multidisciplinary high-throughput skin clinic on healthcare costs of organ transplant recipients.

BACKGROUND: A long-term complication among organ transplant recipients (OTRs) is skin malignancies which are associated with level and duration of immunosuppressive treatment, sun exposure and age. Dermatological surveillance is recommended for OTRs at high risk of skin malignancies, but evidence is lacking on the benefits of such services. OBJECTIVE: To examine the economic impact on patients and on the hospital service of a multidisciplinary high-throughput skin cancer clinic in Brisbane, Australia, dedicated to dermatological and surgical care of high-risk OTRs. METHODS: In a pre/postdesign, hospital admission and cost data were obtained for 101 consecutively enrolled study participants from 12 months prior to the introduction of the clinic (to February 2016), the 3-month 'run-in' period (March to May 2016) and 12 months subsequent (to June 2017). Differences between pre- and post-clinic hospital costs were tested using non-parametric bootstrapping and interrupted time series analysis. A survey of patient out-of-pocket costs and perceived financial burden was also undertaken during the clinic. RESULTS: Overall hospital costs were higher after the clinic but 3-monthly hospital costs for skin procedures trended downwards. Despite 3-monthly mean, hospital visits increasing from 85 to 314, mean 3-monthly costs reduced by AU$1491 (P < 0.001) indicating greater cost efficiency. Total patient out-of-pocket costs were AU$18 377 over 3 months. CONCLUSION: Clinical costing data revealed higher, more rapid throughput and significantly lower per patient costs pre- and postestablishment of a multidisciplinary skin cancer clinic for OTRs.

Uterus transplants and the insufficient value of gestation.

Uterus transplants provide another treatment for infertility. Some might think that we should embrace such transplants as one more way to assist people to have children. However, in this paper I argue that uterus transplants are not something that we ought to fund, nor something that we should make easy to access. First, I argue that any justification of providing uterus transplants must be based on the value of the experience of gestation, rather than on claims of meeting medical need or promoting normal functioning. Second, I demonstrate that such a justification has limited prospects of success. The value of experiencing gestation is unlikely to be sufficient to justify state funding of uterus transplants and, further, we have reason to refrain from enabling such transplants.

Financing uterus transplants: The United States context.

The first baby has successfully been born by uterus transplantation (UTx) in the United States and the procedure is swiftly becoming a viable clinical option for patients with uterine factor infertility (UFI). This raises a practical ethical question: should health insurers finance UTx and what issues should they consider in coming to this decision? The article lays forth some of the factors that shape the decision over whether to finance UTx in the United States, including what procedures must be covered, whether UTx is more like organ transplantation or infertility treatment (which are treated differently in the United States), and the benefits and alternatives of the procedure. Then, the article explores arguments around why UTx should be financed, or at least considered along with other important medical needs. The paper argues that UTx ought to be considered along with other competing claims for healthcare services. In countries that generously cover other infertility services, it may logically follow that medical services that enable gestation should be insured when the healthcare system covers services to conceive. In the United States, however, many groups have long suffered inadequate access to medical care, in the context of infertility and more broadly. U.S. healthcare may need to be made more widely equitable, before covering UTx is seen as financially or politically possible.