Cost minimization analysis of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

BACKGROUND: Trials describing 4-12 week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R-transplants), may be limited in application by costs and delayed access to expensive DAAs. A short prophylactic strategy may be safer and cost-effective. Here, we report a cost minimization analysis using the health system perspective to determine the least expensive DAA regimen, using available published strategies. OBJECTIVES: To conduct cost-minimization analyses (CMAs) from the health system perspective of four DAA regimens to prevent and/or treat HCV transmission from D+/R-kidney transplants. METHODS: CMAs comparing 4 strategies: 1) 7-day prophylaxis with generic sofosbuvir/velpatasvir (SOF/VEL), with 12-week branded glecaprevir/pibrentasvir (G/P) for those with transmission; 2) 8-day branded G/P prophylaxis, with 12-week branded SOF/VEL/voxilaprevir for those with transmission; 3) 4-week perioperative generic SOF/VEL prophylaxis, with 12-week branded G/P for those with transmission; and 4) 8-week branded G/P "transmit-and-treat." We included data from published literature to estimate the probability of viral transmission in patients who received DAA prophylaxis, and assumed a 100% transmission rate for those who received the "transmit-and-treat" approach. RESULTS: In base-case analyses, strategies 1 (expected cost [EC]: $2326) and 2 (expected cost: $2646) were less expensive than strategies 3 (EC: $4859) and 4 (EC: $18,525). Threshold analyses for 7-day SOF/VEL versus 8-day G/P suggested that there were reasonable input levels at which the 8-day strategy may be least costly. The threshold values for the SOF/VEL prophylaxis strategies (7-day vs. 4- week) indicated that the 4-week strategy is unlikely to be less costly under any reasonable value of the input variables. CONCLUSIONS: Short duration DAA prophylaxis using 7 days of SOF/VEL or 8 days of G/P has the potential to yield significant cost savings for D+/R- kidney transplants.

Community pharmacists in Virginia dispensing naloxone under a standing order: A qualitative study.

BACKGROUND: In 2016, the Virginia Health Commissioner signed a standing order into law allowing licensed pharmacists to dispense opioid receptor antagonists (ORAs) for overdose reversal. OBJECTIVES: Using the theory of planned behavior as an initial guide to study development, the aim of this qualitative study was to explore community pharmacists' attitudes, subjective norm, perceived behavioral control, and behavioral intention toward dispensing ORAs under a standing order in Virginia. METHODS: Semi-structured interviews were conducted with community pharmacists across the Commonwealth between June 2018 and October 2019. Interviews were recorded, transcribed verbatim, and thematically analyzed. RESULTS: Twenty-one community pharmacists were interviewed. Pharmacists were confused about the specifics and the processes involved with dispensing naloxone under the standing order. Furthermore, many recognized the underuse of the standing order. Positive attitudes focused on the life-saving action of ORAs. Negative attitudes included encouraging risky behaviors by patients, negatively affecting the patient-pharmacist relationship, offending or contributing to stigmatizing patrons, and having liability issues to the pharmacy. Subjective norms regarding dispensing of ORAs under the standing order were perceived to be favorable among peer pharmacists and primary care and emergency department physicians but may be seen as profit-seeking by patients. Barriers to service provision included lack of guidance from corporate offices (in chain pharmacies), inadequate training, patient out-of-pocket costs, reimbursement issues, inadequate staffing and time, and stigma. Facilitators comprised the existence of practice site-specific protocols, the REVIVE! training, technician support, increased community awareness, physician collaboration, pharmacist training, and employer guidance. Whereas some pharmacists intended to become more familiarized with the standing order, others did not intend to actively identify patients who were at risk of an opioid overdose. CONCLUSION: Pharmacists expressed mixed behavioral intention toward dispensing ORAs under the standing order. Future research should focus on quantifying the uptake of the standing order at the state level.

Potential cost savings by prevention of adverse drug events with a novel medication review program.

OBJECTIVES: Preventable adverse drug events (ADEs) account for appreciable health care costs and patient morbidity and offer an attractive opportunity for health care providers to improve patient care and decrease costs. It has been suggested that pharmacist intervention can prevent admissions and readmissions due to ADEs. This study assessed the ADEs prevented through a novel medication review program, then estimated the potential cost savings of the prevented ADEs using the literature on cost and prevalence of ADEs that were treated. METHODS: An innovative pharmacist-run medication review was implemented in 2 pharmacies from November 2016 to July 2017. Patients with diabetes, chronic obstructive pulmonary disease, congestive heart failure, prior myocardial infarction, or stroke were included. Pharmacists recorded information about each potential ADE prevented using a standard tracking form which was de-identified and retrospective cost analysis was conducted. Estimates of ADE cost and prevalence requiring treatment were extracted from the literature and incorporated into a model to estimate the potential savings in prevented ADEs overall and per patient. Because ADE costs vary with severity, ADEs in this study were scored for potential severity. RESULTS: This study included 436 patients with a total of 272 likely and 385 likely or possible ADEs identified. ADEs prevented resulted in an estimated total potential savings of $94,832 (sensitivity analysis [SA]: $2261-$828,921) for likely ADEs and $138,914 (SA: $13,520-$264,308) for likely and possible ADEs. Per patient estimated medication review savings were $218 (SA: $5-$1901) for likely ADEs and $319 (SA: $31-$606) for likely and possible ADEs. The benefit of potential cost savings from providing this medication review was 3.6-5.3 times the pharmacists' time and salary cost. CONCLUSIONS: Pharmacists in this study identified a numerous potential ADEs. By intervening to prevent these ADEs, pharmacists could generate substantial cost savings.

Prevalence and Characteristics of Pediatric Opioid Exposures and Poisonings in the United States.

OBJECTIVE: To examine the prevalence and characteristics of pediatric opioid exposures and poisonings in the US. STUDY DESIGN: This was a retrospective, cross-sectional analysis using the National Poison Data System from January 1, 2010 to December 31, 2014. Records of children aged <18 years with exposure to opioid-containing medications were identified. Standardized prevalence rates were calculated, and the annual trend was examined. Pediatric opioid exposures were characterized descriptively, and logistic regression was performed to estimate the association between various clinical and sociodemographic characteristics and exposures with serious (ie, moderate, major, or death) outcomes. The association of pediatric opioid exposures and area-level socioeconomic status factors at 5-digit ZIP code level was examined descriptively. RESULTS: The prevalence of opioid exposures was 22.6 per 100 000 children and was particularly high among ≤5-year-olds. Prevalence declined from 25.5 to 20 per 100 000 children from 2010 to 2014. There were 83 418 pediatric opioid exposures over the 5-year period and nearly one-half resulted in poisoning. Over 60% of exposures were among children ≤5 years of age, 73.4% were unintentional, and over 90% occurred at home. One in every 2 pediatric opioid exposures was evaluated in a healthcare facility. Annually 4912 children aged ≤5 years were treated in the emergency department or admitted for care. Older age, nonaccidental intent, and single-substance opioid, especially buprenorphine and methadone, were associated with serious outcomes (P < .05). Positive correlations were observed for area-level socioeconomic status factors including proportion of adults and pediatric opioid exposures. CONCLUSIONS: Pediatric opioid exposures and poisonings decreased from 2010 to 2014 but morbidity remains high. The epidemiology of opioid exposures differed considerably by age.

Cost-effectiveness of hepatitis C-positive donor kidney transplantation for hepatitis C-negative recipients with concomitant direct-acting antiviral therapy.

Pilot studies suggest that transplanting hepatitis C virus (HCV)-positive donor (D+) kidneys into HCV-negative renal transplant (RT) recipients (R-), then treating HCV with direct-acting antivirals (DAA) is clinically feasible. To determine whether this is a cost-effective approach, a decision tree model was developed to analyze costs and effectiveness over a 5-year time frame between 2 choices: RT using a D+/R- strategy compared to continuing dialysis and waiting for a HCV-negative donor (D-/R-). The strategy of accepting a HCV+ organ then treating HCV was slightly more effective and substantially less expensive and resulted in an expected 4.8 years of life (YOL) with a cost of ≈$138 000 compared to an expected 4.7 YOL with a cost of ≈$329 000 for the D-/R- strategy. The D+/R- strategy remained dominant after sensitivity analyses including the difference in RT death probabilities or acute rejection probabilities between using D+ vs D- kidney; time that D-/R- patients waited for RT; dialysis death probabilities while waitlisted for RT in the D-/R- strategy; DAA therapy expected cure rate; costs of transplant, immunosuppressives, DAA therapy, dialysis, or acute rejection. The D+/R- strategy followed by treatment with DAA is less costly and slightly more effective compared to the D-/R- strategy.

Risk Factors for Serious Prescription Opioid-Induced Respiratory Depression or Overdose: Comparison of Commercially Insured and Veterans Health Affairs Populations.

Objective: To characterize the risk factors associated with overdose or serious opioid-induced respiratory depression (OIRD) among medical users of prescription opioids in a commercially insured population (CIP) and to compare risk factor profiles between the CIP and Veterans Health Administration (VHA) population. Subjects and Methods: Analysis of data from 18,365,497 patients in the IMS PharMetrics Plus health plan claims database (CIP) who were dispensed a prescription opioid in 2009 to 2013. Baseline factors associated with an event of serious OIRD among 7,234 cases and 28,932 controls were identified using multivariable logistic regression. The CIP risk factor profile was compared with that from a corresponding logistic regression among 817 VHA cases and 8,170 controls in 2010 to 2012. Results: The strongest associations with serious OIRD in CIP were diagnosed substance use disorder (odds ratio [OR] = 10.20, 95% confidence interval [CI] = 9.06-11.40) and depression (OR = 3.12, 95% CI = 2.84-3.42). Other strongly associated factors included other mental health disorders; impaired liver, renal, vascular, and pulmonary function; prescribed fentanyl, methadone, and morphine; higher daily opioid doses; and concurrent psychoactive medications. These risk factors, except depression, vascular disease, and specific opioids, largely aligned with VHA despite CIP being substantially younger, including more females and less chronic disease, and having greater prescribing prevalence of higher daily opioid doses, specific opioids, and most selected nonopioids. Conclusions: Risk factor profiles for serious OIRD among US medical users of prescription opioids with private or public health insurance were largely concordant despite substantial differences between the populations in demographics, clinical conditions, health care delivery systems, and clinical practices.

Self-reported financial burden of cancer care and its effect on physical and mental health-related quality of life among US cancer survivors.

BACKGROUND: Cancer-related financial burden has been linked to cancer survivors (CS) forgoing/delaying medical care, skipping follow-up visits, and discontinuing medications. To the authors' knowledge, little is known regarding the effect of financial burden on the health-related quality of life of CS. METHODS: The authors analyzed 2011 Medical Expenditure Panel Survey data. Financial burden was present if one of the following problems was reported: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices. The following outcomes were evaluated: Physical Component Score (PCS) and Mental Component Score (MCS) of the 12-Item Short-Form Health Survey (SF-12), depressed mood, psychological distress, and worry related to cancer recurrence. The authors also assessed the effect of the number of financial problems on these outcomes. RESULTS: Of the 19.6 million CS analyzed, 28.7% reported financial burden. Among them, the average PCS (42.3 vs 44.9) and MCS (48.1 vs 52.1) were lower for those with financial burden versus those without. In adjusted analyses, CS with financial burden had significantly lower PCS (ß = -2.45), and MCS (ß = -3.05), had increased odds of depressed mood (odds ratio, 1.95), and were more likely to worry about cancer recurrence (odds ratio, 3.54). Survivors reporting ≥ 3 financial problems reported statistically significant and clinically meaningful differences (≥3 points) in the mean PCS and MCS compared with survivors without financial problems. CONCLUSIONS: Cancer-related financial burden was associated with lower health-related quality of life, increased risk of depressed mood, and a higher frequency of worrying about cancer recurrence among CS.

Prevalence of Antidiabetic and Antilipidemic Medications in Children and Adolescents Treated With Atypical Antipsychotics in a Virginia Medicaid Population.

BACKGROUND: Atypical antipsychotic use among children and adolescents is a cause for concern secondary to metabolic adverse effects. There have been reports of weight gain, metabolic syndrome, dyslipidemia, glucose abnormalities, and decreased insulin sensitivity in children aged 4 to 19 years using atypical antipsychotics. OBJECTIVE: To determine the prevalence of antidiabetic and antilipidemic medication use among children and adolescents receiving atypical antipsychotics and to evaluate whether the odds of receiving antidiabetic and antilipidemic medication differs among atypical antipsychotic agents. METHODS: This retrospective cross-sectional study included Virginia Medicaid beneficiaries (2-17 years) continuously enrolled from August 1, 2010, to July 31, 2011. The participants were categorized into atypical antipsychotic exposed and unexposed. The prevalence of antidiabetic and antilipidemic medication use within the groups was computed. Logistic regression was used to calculate the odds of receiving antidiabetic or antilipidemic medication after controlling for age, sex, and race. RESULTS: A total of 299593 and 4922 beneficiaries were identified in unexposed and exposed groups, respectively. The prevalence of antidiabetic medication use was 0.32% in the unexposed and 1.40% in the exposed group (P < 0.0001). Prevalence of antilipidemic medication use was 0.09% in the unexposed and 0.35% in the exposed group (P < 0.0001). Risperidone and quetiapine users had lower odds than olanzapine users of receiving antidiabetic medication. No differences between the odds of receiving antilipidemic medication among the different antipsychotics (P = 0.1653) were observed. CONCLUSIONS: Prevalence of antidiabetic and antilipidemic medication use was significantly higher among children and adolescent atypical antipsychotic users in a Virginia Medicaid population.

Longitudinal medication adherence group-based trajectories of aging adults in the US: A retrospective analysis using monthly proportion of days covered calculations.

BACKGROUND: It is thought that half of the patients with chronic conditions are not adherent to their medications, which contributes to significant health and economic burden. Many studies estimate medication non-adherence by implementing a threshold of ≥80% of Proportion of Days Covered (PDC), categorizing patients as either adherent or non-adherent. Healthcare quality metrics pertaining to medication use are based on this dichotomous approach of medication adherence, including the Medicare Part D Star Ratings. Among others, the Medicare Part D Star Ratings rewards part D plan sponsors with quality bonus payments based on this dichotomous categorization of beneficiaries' medication adherence. OBJECTIVES: Describe the longitudinal adherence trajectories of adults ≥65 years of age covered by Medicare for 3 classes of drugs in the Part D Star Ratings: diabetes medications, statins, and select antihypertensives. METHODS: This study used Medicare healthcare administrative claims data linked to participants from the Health Retirement Study between 2008 and 2016. Group-based trajectory models (GBTM) elicited the number and shape of adherence trajectories from a sample of N = 11,068 participants for the three pharmacotherapeutic classes considered in this study. Medication adherence was estimated using monthly PDC. RESULTS: GBTM were estimated for the sample population taking antihypertensives (n = 7,272), statins (n = 8,221), and diabetes medications (n = 3,214). The hypertension model found three trajectories: high to very high adherence (47.55%), slow decline (32.99%), and rapid decline (19.47%) trajectories. The statins model found 5 trajectories: high to very high adherence (35.49%), slow decline (17.12%), low then increasing adherence (23.58%), moderate decline (12.62%), and rapid decline (11.20%). The diabetes medications model displayed 6 trajectories: high to very high adherence (24.15%), slow decline (16.84%), high then increasing adherence (25.56%), low then increasing (13.58%), moderate decline (10.60%), and rapid decline (9.27%). CONCLUSIONS: This study showed the fluid nature of long-term medication adherence to the medications considered in the Medicare Part D Star Ratings and how it varies by pharmacotherapeutic class. These challenge previous assumptions about which patients were considered adherent to chronic medications. Policy and methodological implications about medication adherence are discussed.

The economic burden of opioid-related poisoning in the United States.

OBJECTIVE: To estimate the yearly economic burden of opioid-related poisoning in the United States. BACKGROUND: Rates of opioid poisoning and related mortality have increased substantially over the past decade. Although previous studies have measured the costs of misuse and abuse, costs related specifically to opioid poisoning have not been quantified. This study quantifies the economic burden of opioid poisoning in the United States to help evaluate the economic case for efforts to reverse or prevent opioid poisoning and its associated morbidity and mortality. METHODS: Mean costs and prevalence estimates were estimated using publically available datasets. A societal perspective was assumed and accordingly estimated direct medical and productivity costs. Direct medical costs included treatment for opioid poisoning in the emergency department (ED) and inpatient settings, along with emergency transport and drug costs. Productivity costs were estimated using the human capital method and included lost wages due to mortality and absenteeism costs from ED visits and hospitalizations. All costs were inflated to 2011 U.S. dollars. RESULTS: In 2009, total costs were estimated at approximately $20.4 billion with indirect costs constituting 89% of the total. Direct medical costs were approximately $2.2 billion. ED costs and inpatient costs were estimated to be $800 million and $1.3 billion, respectively. Absenteeism costs were $335 million and lost future earnings due to mortality were $18.2 billion. CONCLUSION: Opioid-related poisoning causes a substantial burden to the United States each year. Costs related to mortality account for the majority of costs. Interventions designed to prevent or reverse opioid-related poisoning can have significant impacts on cost, especially where death is prevented.

The relationship between palliative radiotherapy and opioid prescribing patterns among patients with metastatic cancer.

BACKGROUND: While randomized trials have established that palliative radiotherapy, especially to bone, can improve qualitative measures of pain, its quantitative relationship to opioid prescribing patterns has remained underexplored. We aimed to identify the association of palliative radiotherapy on opioid prescriptions received among patients with metastatic cancer. METHODS: The Virginia Commonwealth University Institutional Review Board approved retrospective analysis extracted prescription data from all adult patients with metastatic cancer who underwent outpatient palliative external beam radiation therapy at Virginia Commonwealth University Health System from 2008-2018. Institutional prescribing data were used to calculate the average opioid oral morphine milligram equivalent (MME) dose 30, 60 and 90 days both before and after radiotherapy. Univariate and bivariate ordinary least squares (OLS) regression models were used to estimate the relationship of MME changes with clinical, radiation-related, and demographic patient factors. RESULTS: A total of 182 patients met inclusion criteria. Overall, patients required higher opioid doses after radiotherapy, with mean MME 30, 60, and 90 days prior to radiotherapy of 24.6, 20.2, and 16.8 mg, respectively; which increased to 62.9, 77.7 and 82.4 mg post-radiation therapy (P<0.01). Multivariate OLS models predicting the change of MME 60 days pre- and post-radiation treatment showed that younger age and comorbid depression predicted increased MME after radiotherapy. CONCLUSIONS: Patients with metastatic cancer face a relatively high opioid burden, which increases over time, even among those who receive palliative radiation therapy. Patients who are younger and have comorbid depression may have a higher risk of increased opioid burden after radiotherapy.

Estimating the economic burden of food-induced allergic reactions and anaphylaxis in the United States.

BACKGROUND: Food allergy is reported to affect 4% to 6% of children and 1% to 2% of adults in the United States. Every year, allergic reactions result in visits to physicians, emergency departments, and hospitals. However, the economic burden of food-induced allergic reactions is unknown. OBJECTIVE: We sought to estimate the direct medical costs and indirect costs of food-induced allergic reactions and anaphylaxis in the United States. METHODS: Costs were estimated with a bottom-up approach from a societal perspective: the average cost of illness per patient was calculated and multiplied by reported prevalence estimates. Patients with an inpatient admission, emergency department admission, office-based physician visit, or outpatient visit for a food-induced allergic reaction were identified from a list of federally administered 2006 and 2007 databases by using International Classification of Diseases, ninth revision, codes. Indirect costs were quantified by estimating lost productivity in terms of lost earnings caused by absenteeism and mortality of patients or caregivers. Sensitivity analyses were conducted to measure the robustness of the estimates. RESULTS: For 2007, direct medical costs were $225 million, and indirect costs were $115 million. Office visits accounted for 52.5% of costs, and the remainder was split between emergency visits (20%), inpatient hospitalizations (11.8%), outpatient visits (3.9%), ambulance runs (3%), and epinephrine devices (8.7%). Simulations from probabilistic sensitivity analyses suggested mean direct medical costs were $307 million and indirect costs were $203 million. CONCLUSIONS: The economic burden of allergic reactions caused by food and anaphylaxis was an estimated half a billion dollars in 2007. Ambulatory visits accounted for more than half of the costs.

Healthcare costs and resource utilization associated with renal cell carcinoma among older Americans: A longitudinal case-control study using the SEER-Medicare data.

OBJECTIVES: To determine 1-year and 5-year total healthcare costs and healthcare resource (HRU) associated with renal cell carcinoma (RCC) in older Americans, from a healthcare sector perspective. MATERIALS AND METHODS: This was a longitudinal, retrospective cohort study using the Surveillance, Epidemiology and End Results-Medicare linked data (2006-2014), which included older (≥66 years) patients with primary RCC and 1:5 matched noncancer controls. Patients/controls were followed from diagnosis (pseudo-diagnosis for controls) until death or up to loss-to-follow-up (censored). Per-patient average 1-year and 5-year cumulative total and incremental total healthcare costs and HRU were reported. RESULTS: A total of 11,228 RCC patients were matched to 56,140 controls. Per-patient cumulative average 1-year (incremental = $38,291 [$36,417-$40,165]; $57,588 vs. $19,297) and 5-year (incremental = $68,004 [$55,123-$80,885]; $183,550 vs. $115,547) total costs (excluding prescription drug costs) were 3 and 1.6 times higher for RCC vs. controls. These estimates were 3.6 and 1.7 times higher for RCC vs. controls when prescription costs were included in total costs. Prescription drug costs accounted for 8.4% (incremental = $3,715) and 18.1% (incremental = $15,375) of the 1-year and 5-year incremental total costs, respectively. RCC patients had greater cumulative number of hospitalizations, emergency department visits and prescriptions in 1- and 5-years, compared to controls. CONCLUSIONS: Average first year total cost for a patient with incident diagnosis of RCC is substantially higher than that for controls and it varies depending on the stage at diagnosis. Study findings could help in planning future resource allocation and in determining research and unmet needs in this patient population.

Cost-effectiveness of syringe service programs, medications for opioid use disorder, and combination programs in hepatitis C harm reduction among opioid injection drug users: a public payer perspective using a decision tree.

BACKGROUND: The hepatitis C virus (HCV) prevalence rate among injection drug users (IDUs) in North America is 55.2%, with 1.41 million individuals estimated to be HCV-antibody positive. Studies have shown the effectiveness of syringe service programs (SSPs) alone, medications for opioid use disorder (MOUD) alone, or SSP+MOUD combination in reducing HCV transmission among opioid IDUs. OBJECTIVE: To evaluate the cost-effectiveness of SSP alone, MOUD alone, and SSP + MOUD combination in preventing HCV cases among opioid IDUs in the United States. METHODS: We used a decision tree analysis model based on published literature and publicly available data. Effectiveness was presented as the number of HCV cases avoided per 100 opioid IDUs. A micro-costing approach was undertaken and included both direct medical and nonmedical costs. Cost-effectiveness was assessed from a public payer perspective over a 1-year time horizon. It was expressed as an incremental cost-effectiveness ratio (ICER) and an incremental cost savings per HCV case avoided per 100 opioid IDUs compared with cost savings with "no intervention." Costs were standardized to 2019 U.S. dollars. RESULTS: The incremental cost savings per HCV case avoided per 100 opioid IDUs compared with no intervention were as follows: SSP + MOUD combination = $347,573; SSP alone = $363,821; MOUD alone = $317,428. The ICER for the combined strategy was $4,699 compared with the ICER for the SSP group. Sensitivity analysis showed that the results of the base-case cost-effectiveness analysis were sensitive to variations in the probabilities of injection-risk behavior for the SSP and SSP + MOUD combination groups, probability of no HCV with no intervention, and costs of MOUD and HCV antiviral medications. CONCLUSIONS: The SSP + MOUD combination and SSP alone strategies dominate MOUD alone and no intervention strategies. SSP had the largest incremental cost savings per HCV case avoided per 100 opioid IDUs compared with the no intervention strategy. Public payers adopting the SSP + MOUD combination harm-reduction strategy instead of SSP alone would have to pay an additional $4,699 to avoid an additional HCV case among opioid IDUs. Although these harm-reduction programs will provide benefits in a 1-year time frame, the largest benefit may become evident in the years ahead. DISCLOSURES: This research had no external funding. The authors declare no financial interests in this article. Ijioma is a Health Economics and Outcomes Research (HEOR) postdoctoral Fellow with Virginia Commonwealth University and Indivior. Indivior is a pharmaceutical manufacturer of opioid addiction treatment drugs but was not involved in the design, analysis, or write-up of the manuscript.

Economic burden of pediatric prescription opioid poisonings in the United States.

BACKGROUND: Among the different drugs involved in pediatric exposures and poisonings, opioids are the most important, given their rise in nonmedical use. Opioid poisonings in children can result in serious symptoms or complications, including respiratory disorders such as apnea, respiratory failure, and respiratory depression; psychiatric or nervous system disorders such as agitation, seizures, and coma; and cardiac disorders such as tachycardia, bradycardia, and cardiac arrest. Opioid poisonings in children can have delayed onset of symptoms as well as severe and prolonged toxic effects. Many studies have examined the economic burden of opioid poisoning in the general population, but very little is known about the pediatric population. OBJECTIVE: To estimate the economic burden associated with pediatric prescription opioid poisonings. METHODS: This study examined opioid poisonings in pediatric patients, defined as patients aged less than 18 years, for the 2012 base year. Costs were estimated using the 2012 Nationwide Emergency Department Sample (NEDS), Kids' Inpatient Database (KID), Multiple Cause-of-Death (MCOD) file, and other published sources, while applying a societal perspective. The Bottom Up approach was used to estimate the total cost of pediatric prescription opioid poisonings. Direct costs included costs associated with emergency department (ED) visits, hospitalizations, and ambulance transports. Indirect costs were estimated using the human capital method and included productivity costs due to caregivers' absenteeism and premature mortality among children. Descriptive statistics were employed in calculating costs. RESULTS: The total costs of pediatric prescription opioid poisonings and exposure in the United States were $230.8 million in 2012. Total direct costs were estimated to be over $21.1 million, the majority resulting from prescription opioid poisoning-related inpatient stays. Total indirect (productivity) costs were calculated at $209.7 million, and 98.6% of these costs were attributed to opioid poisoning-related mortality. Pediatric prescription opioid poisoning-related ED visits, inpatient stays, and deaths were most common in patients aged 13-17 years and those in mid to large urban areas. Most were unintentional. CONCLUSIONS: Pediatric prescription opioid poisonings resulted in direct and indirect costs of $230.8 million in 2012. While these costs are low in comparison with the costs of prescription opioid poisoning in the general population, the number of pediatric poisonings represents only a small fraction of total poisonings. Quantified costs associated with pediatric prescription opioid poisonings can help decision makers to understand the economic trade-offs in planning interventions. DISCLOSURES: This research had no external funding but was funded by an unrestricted research grant made to the Department of Pharmacotherapy & Outcomes Science by kaléo Pharma, maker of a naloxone product. The authors declare no conflicts of interest or financial interests. Portions of this study were presented as an abstract at the 22nd Annual ISPOR Meeting; May 22, 2017; Boston, MA.

Good research practices for measuring drug costs in cost-effectiveness analyses: a managed care perspective: the ISPOR Drug Cost Task Force report--Part III.

OBJECTIVES: The objective of this report is to provide guidance and recommendations on how drug costs should be measured for cost-effectiveness analyses conducted from the perspective of a managed care organization (MCO). METHODS: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (DCTF) was appointed by the ISPOR Board of Directors. Members were experienced developers or users of CEA models. The DCTF met to develop core assumptions and an outline before preparing a draft report. They solicited comments on drafts from external reviewers and from the ISPOR membership at ISPOR meetings and via the ISPOR Web site. RESULTS: The cost of a drug to an MCO equals the amount it pays to the dispenser for the drug's ingredient cost and dispensing fee minus the patient copay and any rebates paid by the drug's manufacturer. The amount that an MCO reimburses for each of these components can differ substantially across a number of factors that include type of drug (single vs. multisource), dispensing site (retail vs. mail order), and site of administration (self-administered vs. physician's office). Accurately estimating the value of cost components is difficult because they are determined by proprietary and confidential contracts. CONCLUSION: Estimates of drug cost from the MCO perspective should include amounts paid for medication ingredients and dispensing fees, and net out copays, rebates, and other drug price reductions. Because of the evolving nature of drug pricing, ISPOR should publish a Web site where current DCTF costing recommendations are updated as new information becomes available.

Good research practices for measuring drug costs in cost effectiveness analyses: issues and recommendations: the ISPOR Drug Cost Task Force report--Part I.

OBJECTIVES: The assignment of prices or costs to pharmaceuticals can be crucial to results and conclusions that are derived from pharmacoeconomic cost effectiveness analyses (CEAs). Although numerous pharmacoeconomic practice guidelines are available in the literature and have been promulgated in many countries, these guidelines are either vague or silent about how drug costs should be established or measured. This is particularly problematic in pharmacoeconomic studies performed from the "societal" perspective, because typically the measured cost of a brand name pharmaceutical is not a true economic cost but also includes transfer payments from some members of society (patients and third party payers) to other members of society (pharmaceutical manufacturer stockholders) in large part as a reward for biomedical innovation. Moreover, there are numerous and complex institutional factors that influence how drug costs should be measured from other CEA perspectives, both internationally and within the domestic US context. The objective of this report is to provide guidance and recommendations on how drug costs should be measured for CEAs performed from a number of key analytic perspectives. METHODS: ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (Drug Cost Task Force [DCTF]) was appointed with the advice and consent of the ISPOR Board of Directors. Members were experienced developers or users of CEA models, worked in academia, industry, and as advisors to governments, and came from several countries. Because how drug costs should be measured for CEAs depend on the perspectives, five Task Force subgroups were created to develop drug cost standards from the societal, managed care, US government, industry, and international perspective. The ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (DCTF) subgroups met to develop core assumptions and an outline before preparing six draft reports. They solicited comments on the outline and drafts from a core group of 174 external reviewers and more broadly from the membership of ISPOR at two ISPOR meetings and via the ISPOR web site. RESULTS: Drug cost measurements should be fully transparent and reflect the net payment most relevant to the user's perspective. The Task Force recommends that for CEAs of brand name drugs performed from a societal perspective, either 1) CEA analysts use a cost that more accurately reflects true societal drug costs (e.g., 20-60% of average sales price), or when that is too unrealistic to be meaningful for decision-makers, 2) refer to their analyses as from a "limited societal perspective." CEAs performed from a payer perspective should use drug prices actually paid by the relevant payer net of all rebates, copays, or other adjustments. When such price adjustments are confidential, the analyst should apply a typical or average discount that preserves this confidentiality. CONCLUSIONS: Drug transaction prices not only ration current use of medication but also ration future biomedical research and development. CEA researchers should tailor the appropriate measure of drug costs to the analytic perspective, maintain clarity and transparency on drug cost measurement, and report the sensitivity of CEA results to reasonable drug cost measurement alternatives.

Evaluation of health plan member use of an online prescription drug price comparison tool.

BACKGROUND: Health plans have implemented tiered copayment systems to incentivize members to use less expensive medications. However, members need drug price information to make comparisons among therapeutic alternatives. Many health plans and pharmacy benefit management companies have implemented online prescription drug price comparison tools to provide such information. There has been little published evaluation of these tools. OBJECTIVE: To evaluate use of an online price comparison tool- MyPharmacyTools (MPT)- by the measures of (a) the extent to which the tool was used, (b) changes in use over the first year after implementation, and (c) the types of members who were most likely to use the tool. METHODS: Data were provided by a 500,000-member integrated health plan with approximately 156,250 enrolled families. The sample included only families with continuous eligibility for all members from July 1, 2006, through June 30, 2008; use of 1 of 7 common copayment structures; and use of the pharmacy benefit in every quarter of the study period. Data collected on each member, using pharmacy claims for the time period July 1, 2007, through June 30, 2008, included annual drug costs (total, out-of-pocket, plan-paid, and mail order) and number of unique drugs and unique generic drugs taken during the third quarter of 2007. Data collected also included whether the member had each of several selected chronic diseases (as inferred from drug claims for the third quarter of 2007) and demographics. Age, gender, and family size were taken from eligibility files. Other demographic data were imputed to members from the demographics of the ZIP code in which they resided. MPT was made available to members on July 1, 2007. Use of MPT was measured as the number of times members logged into the site for each quarter during the subsequent year. Statistical analyses were conducted at the family rather than at the individual level, and families were defined as users if any family member used MPT at least once during the year. Between-group comparisons were evaluated with t-tests, Pearson chi-square tests, and analyses of variance. RESULTS: Data were analyzed for 8,909 families composed of 28,537 health plan members, of which 464 (5.2%) families used MPT at least once between July 2007 and June 2008. A total of 141 families used MPT in the first quarter it was available, 170 families used it in the second quarter, 185 families in the third quarter, and 182 families during the fourth quarter. Users had significantly higher mean [SD] total drug costs ($4,477 [$9,647] vs. $2,848 [$3,473], P < 0.001) and used significantly more unique drug products (7.7 [5.7] vs. 5.9 [4.5], P < 0.001) and unique generic drug products (5.0 [3.9] vs. 3.9 [3.2], P < 0.001) than did nonusers. Users were significantly more likely than nonusers to use drugs for behavioral diseases (47.0% vs. 39.7%, P = 0.002), hypercholesterolemia (35.8% vs. 27.0%, P < 0.001), gastric disorders (32.8% vs. 23.0%, P < 0.001), diabetes (18.3% vs. 12.8%, P < 0.001), epilepsy (21.1% vs. 10.6%, P < 0.001), cardiovascular problems (48.3% vs. 37.5%, P < 0.001), and asthma (14.0% vs. 10.7%, P = 0.025). Families that used MPT were less likely to have a female subscriber than were nonusers (39.7% vs. 49.0%, P < 0.001). Otherwise, here were no statistically significant demographic differences between users and nonusers. Families using MPT in more quarters of the year had higher out-of-pocket (P < 0.001) and mail order drug costs (P < 0.001), took a larger number of drugs (P = 0.003) and generic drugs (P = 0.019), were more likely to use drugs for diabetes (P = 0.049) and cardiovascular disease (P = 0.013), and used drugs for a greater number of chronic diseases (P = 0.049), compared with less frequent MPT users. CONCLUSIONS: About 5% of families in a sample from a large integrated health plan used an online prescription drug cost comparison tool during the first year it was available. Use increased over the year. Users were more likely to have several chronic diseases, took more prescription drugs, and had higher drug costs than nonusers. Further, users with more chronic diseases and more prescriptions were more likely to use the tool consistently throughout the year. These results indicate that the tool was successful in reaching health plan members who could most benefit from comparative prescription drug price information.

Should the United States government regulate prescription prices? A critical review.

Prescription drug pricing in the United States continues to generate considerable debate. This critical review and commentary summarizes the evidence surrounding four factors often cited as contributing to high drug prices and/or as rationale for increasing government involvement in drug prices: (1) pharmaceutical industry profits, (2) government funding of basic and biomedical research, (3) "me-too" products, and (4) pharmaceutical advertising. Furthermore, it describes the potential impact of increased governmental regulations on prices and innovation in the pharmaceutical industry. Literature indicates that drug companies have consistently made higher profits than companies in other industries. Research suggests that the magnitude of that difference may be smaller than typically reported due to treatment of research and development (R&D) and marketing and promotional expenses. Research provides inconsistent results on the magnitude of that difference and the need for higher profits to compensate for the industry's level of risk. Evidence suggests that me-too drugs effectively decrease innovator products' period of market exclusivity and may modestly reduce drug prices directly or by increasing manufacturer rebates. The direct impact of advertising expenditures on drug prices is likely limited. The literature suggests that restrictions on advertising and me-too drug development would have minimal effects on prices. Government involvement in pricing products developed from government-funded research has been tried and found neither effective nor workable. These findings suggest that more widespread price regulation would likely result in decreased R&D and fewer new products. The impact of reduced R&D would, in turn, depend on the degree to which lower profits and R&D investments would stymie the development high-value, innovative new products or simply decrease the output of low-value duplicative products. In summary, this critical review of the literature found little evidence that targeted or broad government regulation of prescription prices in the United States would provide net positive societal benefits.

Economic burden of renal cell carcinoma among older adults in the targeted therapy era.

OBJECTIVE: This study examined the economic burden of renal cell carcinoma (RCC) among older adults. The study also examined healthcare costs by types of resources used and stage at which RCC was diagnosed. METHODS: The study analyzed the Surveillance Epidemiology and End Result-Medicare linked data. We included a prevalent cohort of RCC patients from 2013, diagnosed and continuously enrolled in Medicare from 2005 to 2013. RCC patients were matched to controls selected from a 5% sample of noncancer beneficiaries using propensity score matching to calculate incremental costs. Total healthcare costs (THC) were calculated using a phase-based approach, which classified patients into early, continuing, and late phases of care. Costs were also examined by types of resources used and stage at which RCC was diagnosed. Generalized linear models estimated annual incremental costs per patient. The number of older RCC patients was calculated using SEER-Stat and ProjPrev software. The average incremental THC was multiplied by the estimated number of RCC patients to calculate the total economic burden of RCC among older adults. RESULTS: The study included 10,392 each of RCC and control patients. The average annual THC associated with RCC was $7,419 for all phases, $22,752 for the initial phase, $4,860 for the continuing phase, and $13,232 for the late phase of care. The average THC was $4,584 for patients diagnosed at stage I, $4,727 for stage II, $9,331 for stage III, and $31,637 for stage IV. For patients diagnosed at stages I to III, hospital cost (approximately $1,500-$3,400) was the largest component of THC. For stage IV patients, prescription drug cost ($11,747) was the largest component of THC. The projected number of older RCC patients in 2015 was 204,256. The annual economic burden of RCC after weighting for proportion of patients diagnosed at various stages was estimated to be $2.1 billion. CONCLUSIONS: RCC was associated with a significant economic burden on Medicare. Healthcare costs associated with RCC varied substantially between early stage and metastatic patients. This research provided a baseline that can be used to assess the economic value of emerging therapies among older RCC patients.