Cost estimation alongside a multi-regional, multi-country randomized trial of antenatal ultrasound in five low-and-middle-income countries.

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).

Challenges in the value assessment, pricing and funding of targeted combination therapies in oncology.

BACKGROUND: The use of targeted combination therapy (TCT) is becoming the standard of care in oncology as cancers are attacked through multiple inhibition mechanisms. TCTs pose a budget challenge to health systems and an economic return challenge for companies developing them. METHODS: We conducted a systematic literature review to identify challenges specific to TCTs and reviewed publicly available reports by health technology assessment and pricing and reimbursement bodies. We synthesized our findings into a problem map. RESULTS AND DISCUSSION: Challenges and policy solutions linked to TCTs remain almost fully unexplored; we identified few resources that explicitly addressed TCTs. Contributors to the budget challenge are found at different layers; they and include static willingness-to-pay (WTP) for TCTs and inefficiencies in managing prices of backbone therapies. Economic return challenges are related to payer-imposed restrictions, peculiarities of TCT development, and conflicting incentives of pharmaceutical companies that own constituent therapies. Consequences are delayed or restricted patient access to TCTs, disincentives for research and development, and fewer life years gained. CONCLUSIONS: Multiple issues will lead to the unsustainability of funding systems and possible conflict between stakeholders around access to TCTs. To manage these, new value assessment and attribution methodologies, modified trial designs and differentiated WTP thresholds can be considered in ways that are customized to the characteristics of different health systems.

The effects of exenatide bid on metabolic control, medication use and hospitalization in patients with type 2 diabetes mellitus in clinical practice: a systematic review.

The objective of this systematic review was to assess the published literature on the effectiveness of exenatide twice daily (exenatide) in clinical practice, specifically its effects on haemoglobin A1c (A1C), fasting glucose (FG), weight, systolic blood pressure (SBP), medication use, hospitalization and cardiovascular disease (CVD) outcomes. A systematic literature search using the MEDLINE database of English language literature published between January 2005 and May 2011 was performed. The review included retrospective or prospective observational studies that included 100 or more patients per treatment group. A total of 15 studies meeting the inclusion criteria were identified. The studies revealed significant reductions of -0.4 to -0.9% in A1C, -10 mg/dl in FG, -2 to -11 kg in body weight and -2 to -11 mmHg in SBP. Statistically significant reductions in the use or dosage of either oral glucose-lowering medications or insulin after initiating exenatide treatment were found in every observational study that assessed medication changes, including reductions in dosage of up to 75% in sulphonylureas dosages, 22% in metformin, 66% in thiazolidinediones (TZD) or TZD combination therapy and 75% in prandial insulin. Exenatide-treated patients experienced significantly lower rates of all-cause and CVD-related hospitalization and CVD events than patients treated with other therapies overall. In this review of observational studies, exenatide initiation was associated with significant reductions in clinically relevant outcomes. Improvements in A1C, FG, weight and SBP in the observational studies in this review were consistent with improvements observed in controlled clinical trials.

Can modeling of health outcomes facilitate regulatory decision making? The benefit-risk tradeoff for rosiglitazone in 1999 vs. 2007.

Rosiglitazone was initially approved for type 2 diabetes monotherapy. We tested health-outcomes modeling as an aid to regulatory decision making by quantifying the incremental net benefit (INB) value of rosiglitazone (relative to a comparator), both at the time of first approval (1999) and at the FDA advisory committee review (2007). Using 1999 data, rosiglitazone was projected to provide an additional 0.639 years of life (0.373 quality-adjusted life years (QALYs)) relative to placebo but a loss of 0.312 years (0.173 QALYs) relative to glyburide, with uncertainty in reduction of hemoglobin A(1c) (HbA(1c)) level having the greatest impact on the benefit-risk profile. By 2007, rosiglitazone was projected to provide an additional 0.222 years (0.091 QALYs) vs. glyburide and 0.026 years vs. metformin (0.009 QALYs). Modeling suggested that the use of rosiglitazone as monotherapy was not initially warranted, given the uncertainty with regard to benefit. Despite similar net benefit (NB) as metformin shown in postmarketing data, residual cardiovascular (CV) concerns did not support the use of rosiglitazone as first-line therapy. We adapted a mathematical diabetes model to estimate NB and uncertainty of diabetes monotherapy.

Scheduling of measles vaccination in low-income countries: projections of a dynamic model.

Large-scale vaccination campaigns (SIAs) and improved routine immunization (RI) have greatly reduced measles incidence in low-income countries. However, the interval between SIAs required to maintain these gains over the long term is not clear. We developed a dynamic model of measles transmission to assess measles vaccination strategies in Cambodia, Ghana, India, Morocco, Nigeria, and Uganda. We projected measles cases from 2008 to 2050 under (a) holding SIAs every 2, 4, 6, or 8 years, (b) improvements in first dose routine measles vaccine (MCV1) coverage of 0%, 1%, 3% annually, and (c) introducing MCV2 once MCV1 coverage reaches 70%, 80%, 90%. If MCV1 continues improving, then India and Nigeria could hold SIAs every 4 years without significant probability of large outbreaks, and the other countries every 6-8 years. If RI remains stagnant, India and Nigeria should hold SIAs every 2 years, and the other countries every 4-6 years.

Will pharmacogenomics disrupt the U.S. health care system? No.

There is a widely held view that the scientific breakthroughs represented by pharmacogenomics and other new biomarkers portend a new 'personalized medicine' that will disrupt and revolutionize the U.S. health care system. This paper explores this hypothesis, arguing that while this exciting new science will enhance our understanding of human biology and our ability to develop new measures against disease over the long term, there is little reason to expect it to undermine or fundamentally alter the current U.S. health care system. This system is under attack from other, broader societal forces and will necessarily change; however, the argument made here is that the current system can easily cope with the changes that pharmacogenomics will bring and that it is unlikely to be disruptive to the current system because (1) it will probably unfold gradually and incrementally over a time span of decades and (2) our drug development and health care system--from development to delivery--has demonstrated sufficient flexibility to adapt to these kinds of incremental changes. Nonetheless, the sustainability of the projected growth in health spending is in question. Profound reforms are likely, but improved knowledge of our human biology will more likely be a constructive factor as we adapt to these changes.

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial.

Oral capecitabine (Xeloda) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings pound3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings pound1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

The cost effectiveness of mycophenolate mofetil in the first year after primary cadaveric transplant. U.S. Renal Transplant Mycophenolate Mofetil Study Group.

Mycophenolate mofetil (MMF) has been shown to reduce the incidence of acute graft rejection in three controlled trials of cadaveric renal transplantation. In a U.S. trial using quadruple sequential induction therapy as control, the MMF 2-g treatment group had an acute rejection rate 40.6% lower than control in the first posttransplant year (27.9% MMF-treated versus 47.0% control). The purpose of this analysis is to evaluate the economic implications of these clinical differences. The analysis relies on resource use data from the trial and other sources. Medical costs were estimated using a societal perspective and excluded the cost of the transplant procedure and organ acquisition. The two groups were compared in terms of treatment for acute rejection and opportunistic infection, graft survival, dialysis use, and maintenance immunosuppression. The results suggest that, on average, when compared with standard therapy, patients treated with MMF are likely to have lower rejection-related treatment costs because of a lower incidence of rejection ($6237 versus $3702), lower dialysis and graft failure costs because of improved graft survival ($20,104 versus $16,972), no difference in opportunistic infection treatment costs ($1962 versus $1962), and higher additional immunosuppression costs ($855 versus $5170). Taken together, these results suggest that patients treated with MMF are, on average, likely to have slightly lower first-year costs ($29,158 versus $27,807) compared with control, indicating that MMF treatment is cost-effective in the first year. These results remained stable under sensitivity analyses, with plausible variation in the rates of acute rejection, graft survival, and infection.

Cost-effectiveness of repeat medical procedures: kidney transplantation as an example.

The constraints on medical-care resources can give rise to the question of the cost-effectiveness of permitting repeat medical procedures when some patients may die without undergoing even a first procedure. Using kidney transplantation as an example, this study estimates the cost-effectiveness of patients' having available the option of a repeat medical procedure in the event the first procedure fails. Specifically, the analysis examines the effect on transplant candidates of having the option of kidney retransplantation, if and when retransplantation might be needed. Data sources include the U.S. Renal Data System (USRDS) Case-Mix Severity Study, Health Care Financing Administration (HCFA) data, and a MEDLINE search. Outcome measures include life expectancy, quality-adjusted life expectancy, lifetime costs of medical care, and marginal cost-effectiveness from a societal perspective. By avoiding lifelong dialysis after graft failure, first-transplant candidates gain an average of 47 quality-adjusted days with a retransplantation policy, despite the prolongation of time to first transplant by an average of 30 quality-adjusted days. The lifetime cost of medical care per first-transplant candidate is $1,210 higher with a retransplantation policy compared with the no-retransplantation policy; its societal cost-effectiveness is estimated to be $9,656 per quality-adjusted life-year saved. The retransplantation policy provides the greatest improvement in quality-adjusted life expectancy for younger candidates. In the case of kidney transplantation, the cost-effectiveness of a repeat transplant, on average, compares favorably with those of other medical strategies in common practice. As resources become increasingly constrained, this study demonstrates a framework for considering the cost-effectiveness of repeat medical procedures.

Assessment of the effectiveness of supply-side cost-containment measures.

This article assesses the arguments and evidence concerning the likely effectiveness of four supply-side cost-containment measures. The health planning efforts of the 1970s, particularly certificate-of-need regulations, had very limited success in containing costs. The new and related tools of technology assessment and practice guidelines hold some promise for refining benefit packages, but they are inadequate for micromanaging complex medical practices. Payment policies, such as hospital ratesetting, have enjoyed some success in limiting hospital cost growth but are less effective at controlling total costs. None of these measures alone is likely to address fully the fundamental issues of equity and efficiency in health care resource allocation that underlie the problem of rising costs.

Medicaid, the uninsured, and national health spending: federal policy implications.

Implications are discussed for Federal policy of "gap-filling" initiatives at the State and Federal level to deal with the problem of the uninsured. Measures currently under active consideration that involve expansions of Medicaid and employment-related insurance are considered in the light of recent studies of the uninsured and recent simulations of their cost and coverage impacts. The limited impact of these gap-filling measures on additional national health spending, in contrast to program costs and Federal outlays, is emphasized. Placing greater emphasis on this broader societal perspective could assist Federal policymakers in developing an acceptable strategy for covering the uninsured.

Donor availability as the primary determinant of the future of heart transplantation.

Heart transplantation has now achieved a therapeutic status similar to that of cadaveric renal transplantation. Depending on patient selection criteria, it is estimated that as many as 15,000 people per year could conceivably benefit from a heart transplant, but the actual number of persons who will benefit is severely constrained by donor supply. Availability of heart donors was estimated based on data obtained on 1,955 organ donors in the United States. The results show that because of age and other contraindications, only 400 to 1,100 viable donor hearts may be available each year. Donor supply is the most critical determinant of the future of heart transplantation since it will dictate the number of transplants performed, the survival of transplant recipients, the total program expenditures associated with heart transplantation, the nature of the legal and ethical issues involved, the number of cardiac transplant programs required to make optimal use of the available donor hearts, and the future role of mechanical circulatory support systems.

KIE: In the opinion of the authors, heart transplantation has achieved a therapeutic status equivalent to that of cadaveric kidney transplantation; and they estimate that as many as 15,000 patients per year could benefit from transplants. Based on their analysis of data on 1,955 recent organ donors, however, the authors warn that only 400 to 1,100 donor hearts may be available per year for transplantation. Donor supply is seen as the most critical factor in the development of heart transplantation, and the projected shortfall of organs will affect the number of transplants performed, the number of centers needed to perform them, the survival of recipients, the nature of legal and ethical issues involved, and the role of xenografts and mechanical circulatory support systems.

The quality of life of patients with end-stage renal disease.

We assessed the quality of life of 859 patients undergoing dialysis or transplantation, with the goal of ascertaining whether objective and subjective measures of the quality of life were influenced by case mix or treatment. We found that 79.1 per cent of the transplant recipients were able to function at nearly normal levels, as compared with between 47.5 and 59.1 per cent of the patients treated with dialysis (depending on the type). Nearly 75 per cent of the transplant recipients were able to work, as compared with between 24.7 and 59.3 per cent of the patients undergoing dialysis. On three subjective measures (life satisfaction, well-being, and psychological affect) transplant recipients had a higher quality of life than patients on dialysis. Among the patients treated with dialysis, those undergoing treatment at home had the highest quality of life. All quality-of-life differences were found to persist even after the patient case mix had been controlled statistically. Finally, the quality of life of transplant recipients compared well with that of the general population, but despite favorable subjective assessments, patients undergoing dialysis did not work or function at the same level as people in the general population.

Estimating physician requirements for neurology: a needs-based approach.

Applying the adjusted needs-based model developed by the Graduate Medical Education National Advisory Committee (GMENAC), physician requirements in neurology were estimated for the year 1990. A Delphi panel of physician experts estimated appropriate patterns of treatment for 56 neurologic conditions. Their median estimates implied a need for 14,500 neurologists in 1990, suggesting a shortage relative to the projected supply. An advisory panel of former GMENAC members reviewed those estimates and recommended certain adjustments to ensure internal consistency and compatibility with those for other specialties. Adoption of these adjustments significantly reduces requirements, implying a total need for 8,400 neurologists--a figure in near balance with the projected supply of 8,650. The difference between the Delphi and Advisory Panel estimates reflects divergent views, apparent as well among the Delphi panelists, of the appropriate role of neurologists--consultants versus principal care providers.

The supply of and requirements for diagnostic and therapeutic radiologists.

This report summarizes the findings of a national study to examine the future requirements for and supply of radiologists. By 1990, there is expected to be a moderate shortage of the therapeutic radiologists, coupled with a substantial oversupply of diagnostic radiologists.

Interspecialty variation in office-based care.

Analysis of national survey data on physician-patient encounters raises questions about physician education and manpower policy. Data compiled by the University of Southern California Medical Activities and Manpower Projects and the United States Bureau of Health Professionals reveal differences among internists, cardiologists, family practitioners, and pediatricians in procedures used for diagnosing and treating several frequently encountered conditions. Differences are observed in expenditure of time and use of a broad range of diagnostic and therapeutic techniques. These differences remain significant even after several important characteristics of individual physicians, patients, and the practice environment have been controlled. Findings from this study underscore the necessity of reviewing the content of medical education and policies that encourage a broad range of specialists to provide primary care. The findings also emphasize the need to address the physician's knowledge base in promoting changes in practice patterns.

Estimates of physician requirements for 1990 for the specialties of neurology, anesthesiology, nuclear medicine, pathology, physical medicine and rehabilitation, and radiology. A further application of the GMENAC methodology.

The Graduate Medical Education National Advisory Committee (GMENAC) adjusted needs-based model for determining physician requirements was applied to the specialties of anesthesiology, neurology, nuclear medicine, pathology, physical medicine and rehabilitation, and radiology, which had not been completed at the time of the original GMENAC final report. Physical medicine and rehabilitation continues to be projected as a shortage specialty; anesthesiology is in near balance. Neurology and pathology are no longer projected to be specialties of oversupply, but rather to be in near balance. Diagnostic radiology continues to be projected as a specialty of oversupply; therapeutic radiology is projected to be in near balance, as is nuclear medicine. The GMENAC aggregate-requirements estimates are thus revised upward from 466,000 to 473,000 full-time equivalent physicians for 1990, reducing the projected surplus from 15.0% to 13.3%.