Evaluating the Strength of the Association Between Industry Payments and Prescribing Practices in Oncology

Background: Financial relationships between physicians and the pharmaceutical industry are common, but factors that may determine whether such relationships result in physician practice changes are unknown. Materials and Methods: We evaluated physician use of orally administered cancer drugs for four cancers: prostate (abiraterone, enzalutamide), renal cell (axitinib, everolimus, pazopanib, sorafenib, sunitinib), lung (afatinib, erlotinib), and chronic myeloid leukemia (CML; dasatinib, imatinib, nilotinib). Separate physician cohorts were defined for each cancer type by prescribing history. The primary exposure was the number of calendar years during 2013–2015 in which a physician received payments from the manufacturer of one of the studied drugs; the outcome was relative prescribing of that drug in 2015, compared with the other drugs for that cancer. We evaluated whether practice setting at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, receipt of payments for purposes other than education or research (compensation payments), maximum annual dollar value received, and institutional conflict-of-interest policies were associated with the strength of the payment-prescribing association. We used modified Poisson regression to control confounding by other physician characteristics. Results: Physicians who received payments for a drug in all 3 years had increased prescribing of that drug (compared with 0 years), for renal cell (relative risk [RR] 1.81, 95% confidence interval [CI] 1.58–2.07), CML (RR 1.22, 95% CI 1.08–1.39), and lung (RR 1.69, 95% CI 1.58–1.82), but not prostate (RR 0.97, 95% CI 0.93–1.02). Physicians who received compensation payments or >$100 annually had increased prescribing compared with those who did not, but NCI setting and institutional conflict-of-interest policies were not consistently associated with the direction of prescribing change. Conclusion: The association between industry payments and cancer drug prescribing was greatest among physicians who received payments consistently (within each calendar year). Receipt of payments for compensation purposes, such as for consulting or travel, and higher dollar value of payments were also associated with increased prescribing. Implications for Practice: Financial payments from pharmaceutical companies are common among oncologists. It is known from prior work that oncologists tend to prescribe more of the drugs made by companies that have given them money. By combining records of industry gifts with prescribing records, this study identifies the consistency of payments over time, the dollar value of payments, and payments for compensation as factors that may strengthen the association between receiving payments and increased prescribing of that company's drug

Characterizing and assessing antiemetic underuse in patients initiating highly emetogenic chemotherapy

Background: Patients initiating highly emetic chemotherapy (HEC) are at a 90% risk of chemotherapy-induced nausea and vomiting (CINV). Despite guideline-concordant antiemetic prescribing preventing CINV in up to 80% of patients, studies suggest that guideline-concordant antiemetic regimen use by patients initiating HEC is sub-optimal. However, these studies have been limited to single-site or single-cancer type with limited generalizability. The objective of this study was to describe antiemetic fill regimens and to assess predictors of underuse in the USA. Methods: Our study population was adult patients under the age of 65 with cancer initiating intravenous HEC between 2013 and 2015 with employer-sponsored insurance in the IBM Watson/Truven MarketScan Commercial Claims database (N = 31,923). Descriptive statistics were used to explain antiemetic prescribing patterns, including antiemetic underuse. Modified Poisson regression was used to identify factors associated with antiemetic underuse. Results: Among individuals initiating HEC, 49% underused guideline-concordant antiemetics. Most classified as under-using lacked an NK1 fill. While dexamethasone and 5HT3A uptake was over 80%, olanzapine use was minimal. Having lower generosity for prescription and medical benefits (paying more versus less than 20% out-of-pocket) increased the underuse risk by 3% and 4% (RR,1.03; 95% CI,1.01–1.05; P = 0.01 and RR,1.04; CI, 1.00–1.09; P = 0.03), respectively. Additionally, compared to receiving chemotherapy in the physician office setting, patients were at a 28% (RR, 1.28; 95% CI, 1.25–1.30; P < 0.0001) higher underuse risk in the outpatient hospital setting. Conclusion: Antiemetic underuse is high in patients initiating HEC, potentially leading to avoidable CINV events. We found that insurance generosity has a minimal effect on antiemetic guideline concordance in this population, suggesting discordance may be the result of site of care as well as gaps in provider knowledge or accountability

Spending by commercial insurers on chemotherapy based on site of care, 2004-2014

The impact of price variation because of the site of care—receiving treatment in a physician office vs a hospital outpatient department (HOPD)—is an important driver of health care spending. While patients may receive the same treatment in either setting, insurers typically reimburse payments to HOPDs at a higher rate than to physician offices.Hospitals justify this payment difference because they incur higher overhead costs and treat more medically complex patient populations

Out-of-pocket and health care spending changes for patients using orally administered anticancer therapy after adoption of state parity laws

IMPORTANCE Oral anticancer medications are increasingly important but costly treatment options for patients with cancer. By early 2017, 43 states andWashington, DC, had passed laws to ensure patients with private insurance enrolled in fully insured health plans pay no more for anticancer medications administered by mouth than anticancer medications administered by infusion. Federal legislation regarding this issue is currently pending. Despite their rapid acceptance, the changes associated with state adoption of oral chemotherapy parity laws have not been described. OBJECTIVE To estimate changes in oral anticancer medication use, out-of-pocket spending, and health plan spending associated with oral chemotherapy parity law adoption. DESIGN, SETTING, AND PARTICIPANTS Analysis of administrative health plan claims data from 2008-2012 for 3 large nationwide insurers aggregated by the Health Care Cost Institute. Data analysis was first completed in 2015 and updated in 2017. The study population included 63 780 adults living in 1 of 16 states that passed parity laws during the study period and who received anticancer drug treatment for which orally administered treatment options were available. Study analysis used a difference-in-differences approach. EXPOSURES Time period before and after adoption of state parity laws, controlling for whether the patient was enrolled in a plan subject to parity (fully insured) or not (self-funded, exempt via the Employee Retirement Income Security Act). MAIN OUTCOMES AND MEASURES Oral anticancer medication use, out-of-pocket spending, and total health care spending. RESULTS Of the 63 780 adults aged 18 through 64 years, 51.4%participated in fully insured plans and 48.6%in self-funded plans (57.2%were women; 76.8%were aged 45 to 64 years). The use of oral anticancer medication treatment as a proportion of all anticancer treatment increased from 18%to 22%(adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95%CI, 0.96-1.13; P = .34) comparing months before vs after parity. In plans subject to parity laws, the proportion of prescription fills for orally administered therapy without copayment increased from 15.0%to 53.0%, more than double the increase (12.3%-18.0%) in plans not subject to parity (P < .001). The proportion of patients with out-of-pocket spending of more than $100 per month increased from 8.4$19.44 at the 25th percentile, by $32.13 at the 50th percentile, and by$10.83 at the 75th percentile but increased at the 90th ($37.19) and 95th ($143.25) percentiles after parity (all P < .001, controlling for changes in plans not subject to parity). Parity laws did not increase 6-month total spending for users of any anticancer therapy or for users of oral anticancer therapy alone. CONCLUSIONS AND RELEVANCE While oral chemotherapy parity laws modestly improved financial protection for many patients without increasing total health care spending, these laws alone may be insufficient to ensure that patients are protected from high out-of-pocket medication costs

Early Post-Therapy Prescription Drug Usage among Childhood and Adolescent Cancer Survivors

Objective: To describe the patterns of prescription drug use among child and adolescent survivors of cancer in the early post-therapy period compared with matched peers without a cancer history. Study design: Using the MarketScan commercial insurance claims database, we performed a retrospective cohort study identifying survivors of pediatric (0-21 years of age at diagnosis) leukemia, lymphoma, central nervous system, bone, or gonadal cancers who completed therapy from 2000 to 2011 and remained insured for 3 years post-therapy. Prescription fills during the first 3 years post-therapy were examined, categorized by drug class, and compared with age-, sex-, and region-matched individuals without cancer. Results: We identified 1414 survivors and 14 007 comparators. Compared with those without cancer, survivors had 1.5-4.5 times greater risk for filling opioids. Survivors of leukemia, lymphoma, central nervous system, and bone cancers had 2-5 times the risk for antidepressant and 3-7 times the risk for anxiolytic use. Survivors of leukemia, lymphoma, and bone tumors had 3-13 times the risk for angiotensin-converting enzyme inhibitors by the third year post-therapy. Conclusion: Compared with peers without cancer, survivors of childhood cancer have greater rates of prescription use across many drug classes, suggesting greater medical morbidity. Survivors were more likely to use opioid, psychoactive, hormone, and cardiovascular medications. All general pediatricians and subspecialists should be aware of potentially emerging morbidities during the early post-therapy period to guide risk-based surveillance and survivorship care

Comparative toxicity and effectiveness of trastuzumab-based chemotherapy regimens in older women with early-stage breast cancer

Purpose The combination of chemotherapy and trastuzumab is the standard of care for adjuvant treatment of human epidermal growth factor receptor 2-positive breast cancer. Two regimens have been widely adopted in the United States: doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH) and docetaxel, carboplatin, and trastuzumab (TCH). No head-to-head comparison of these regimens has been conducted in a clinical trial, and existing trial data have limited generalizability to older patients. Methods We used SEER-Medicare data from 2005 to 2013 to compare outcomes of ACTH versus TCH among patients age older than 65 years. Propensity score matching was used to balance cohort characteristics between treatment arms. Outcomes included toxicity-related hospitalization, survival, and trastuzumab completion. Data from 1,077 patients receiving ACTH or TCH were analyzed, and the propensity-matched subsample included 416 women. Results There was a significant shift toward TCH over time, with 88% of patients receiving ACTH in 2005 compared with 15% by 2011. Among propensity score-matched patients, we found no difference between regimens in health care use overall or for chemotherapy-related adverse events (ACTH, 34% v TCH, 36.5%; P = .46). Patients receiving TCH were significantly more likely to complete trastuzumab (89% v 77%; P = .001). There was no difference in 5-year breast cancer-specific survival (ACTH, 92% v TCH, 96%; hazard ratio, 2.08; 95% CI, 0.90 to 4.82) or overall survival. Conclusion Among a matched sample of older patients, ACTH compared with TCH was not associated with a higher rate of serious adverse events or hospitalizations, but it was associated with less completion of adjuvant trastuzumab.Wedid not detect a difference in 5-year survival outcomes for ACTH compared with TCH. In the context of limited evidence in older patients, selection between these two regimens on the basis of concerns about differential toxicity or efficacy may not be appropriate

Comparative safety and health care expenditures among patients with chronic myeloid leukemia initiating first-line imatinib, dasatinib, or nilotinib

PURPOSE Tyrosine kinase inhibitors (TKIs) have dramatically improved survival for patients with chronic myeloid leukemia (CML). No overall survival differences were observed between patients initiating first- and second-generation TKIs in trials; however, real-world safety and cost outcomes are unclear. We evaluated comparative safety and health care expenditures between first-line imatinib, dasatinib, and nilotinib among patients with CML. PATIENTS AND METHODS Eligible patients had one or more fills for imatinib, dasatinib, or nilotinib in the MarketScan Commercial and Medicare Supplemental databases between January 1, 2011, and December 31, 2016 (earliest fill is the index date), 6 months pre-index continuous enrollment, CML diagnosis, and no TKI use in the pre-index period. Hospitalizations or emergency department visits (safety events) were compared across treatment groups using propensity-score-weighted 1-year relative risks (RRs) and subdistribution hazard ratios (HRs). Inflation-adjusted annual health care expenditures were compared using quantile regression. RESULTS Eligible patients included 1,417 receiving imatinib, 1,067 receiving dasatinib, and 647 receiving nilotinib. The 1-year risk of safety events was high: imatinib, 37%; dasatinib, 44%; and nilotinib, 40%, with higher risks among patients receiving dasatinib (RR, 1.17; 95% CI, 1.06 to 1.30) and nilotinib (RR, 1.07; 95% CI, 0.93 to 1.23) compared with those receiving imatinib. Over a median of 1.7 years, the cumulative incidence of safety events was higher among patients receiving dasatinib (HR, 1.23; 95% CI, 1.10 to 1.38) and nilotinib (HR, 1.08; 95% CI, 0.95 to 1.24) than among those receiving imatinib. One-year health care expenditures were high (median, $125,987) and were significantly higher among patients initiating second-generation TKIs compared with those receiving imatinib (difference in medians: dasatinib v imatinib,$22,393; 95% CI, $17,068 to$27,718; nilotinib v imatinib, $19,463; 95$14,689 to $24,236). CONCLUSION Patients receiving imatinib had the lowest risk of hospitalization or emergency department visits and 1-year health care expenditures. Given a lack of significant differences in overall survival, imatinib may represent the ideal first-line therapy for patients, on average

Financial toxicity in adults with cancer: Adverse outcomes and noncompliance

Purpose Because of the escalating cost of cancer care coupled with high insurance deductibles, premiums, and uninsured populations, patients with cancer are affected by treatmentrelated financial harm, known as financial toxicity. The purpose of this study was to describe individuals reporting financial toxicity and to identify rates of and reasons for affordability-related treatment noncompliance. Methods From May 2010 to November 2015, adult patients (age $ 18 years) with cancer were identified from a Health Registry/Cancer Survivorship Cohort. Financial toxicity was defined as agreement with the phrase"You have to pay for more medical care than you can afford" from the Patient Satisfaction Questionnaire-18. Logistic regression and Fisher exact tests were used to compare groups. Results Of 1,988 participants, 524 (26%) reported financial toxicity. Patients reporting financial toxicity were more likely age 65 years or younger, female, nonwhite, non-English speaking, not married, less educated, and to have received a diagnosis more recently (all P,.001). Participants with financial toxicity were more likely to report noncompliance with medication, owing to inability to afford prescription drugs (relative risk [RR], 3.55; 95% CI, 2.53 to 4.98), and reported forgoing mental health care (RR, 3.89; 95% CI, 2.04 to 7.45), doctor's visits (RR, 2.98; 95% CI, 1.97 to 4.51), and medical tests (RR, 2.54; 95% CI, 1.49 to 4.34). The most endorsed reasons for delayed care were not having insurance coverage and being unable to afford household expenses. Conclusion More than25%of adultswith cancer reportedfinancial toxicity thatwas associatedwith an increased riskfor medicalnoncompliance.Financial toxicity remains a major issue in cancer care, and efforts are needed to ensure patients experiencing high levels offinancial toxicity are able to access recommended care

Decreased antihyperglycemic drug use driven by high out-of-pocket costs despite medicare coverage gap closure

OBJECTIVE Using the 2016 Medicare Part D coverage gap as an example, we explored effects of increased out-of-pocket costs on adherence to branded dipeptidyl peptidase 4 inhibitors (DPP-4i) in patients without financial subsidies relative to subsidized patients who do not experience increased spending during the gap. We also explored seasonality of reinitiation, because discontinuers may be more likely to reinitiate in January when benefits reset. RESEARCH DESIGN AND METHODS We identified DPP-4i or sulfonylurea initiators, aged ‡66 years, from a 20% sample of 2015–2016 Medicare claims. Difference-in-differences Poisson regression was used to compare adherence before and after entering the coverage gap between nonsubsidizedand subsidized patients.Among discontinuers, monthly hazardratios (HRs) for reinitiation relative to January 2016 were derived with Cox models. As a second control, we repeated analyses using sulfonylureas, generic low-cost alternatives. RESULTS In 2016, 8,096 subsidized and 6,173 nonsubsidized DPP-4i initiators entered the coverage gap. For nonsubsidized patients, copayment in the coverage gap was 45% ($227 per DPP-4i prescription), and adherence decreased from 68.4% to 49.0% after gap entry. Accounting for adherence differences in subsidized patients, nonsubsidized patients demonstrated reduced adherence to DPP-4i (differencein-difference: 216.9%; 95% CI 218.7%, 215.1%) but not sulfonylureas (21.6%; 95% CI 23.4%, 0.2%). Reinitiation was lowest in the months before January (HR 0.4–0.5) among nonsubsidized DPP-4i patients, demonstrating a strong seasonal pattern. CONCLUSIONS Increased out-of-pocket costs negatively affect adherence and reinitiation of branded antihyperglycemic drugs among patients without financial subsidies. Despite closure of the coverage gap, affordability remains a concern given increasing list prices for many drugs on Medicare and the growing use of deductibles and coinsurance by commercial health plans

Oral oncology parity laws, medication use, and out-of-pocket spending for patients with blood cancers

Background: In this study, we sought to estimate the association between oral oncology parity law adoption and anticancer medication use for patients with chronic myeloid leukemia or multiple myeloma. Methods: This was an observational study of administrative claims from 2008 to 2017. Among individuals initiating tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia or immunomodulatory drugs for multiple myeloma, we compared out-of-pocket spending, adherence, and discontinuation before and after parity among individuals in fully insured plans (subject to parity) vs self-funded plans (exempt from parity) using propensity-score weighted difference-in-differences regression models. Results: Among patients initiating TKIs (N = 2082) or immunomodulatory drugs (N = 3326) there were no statistically significant differences in adherence or discontinuation associated with parity. The proportion of patients with initial out-of-pocket payments of $0 increased in fully insured plans after parity from 5.7$100 decreased from 30.3% to 24.7% for TKIs and 30.6% to 27.5% for immunomodulatory drugs in fully insured plans after parity. Relative to changes in self-funded plans, those in fully insured plans were 0.74 (95% CI = 0.54 to 1.01) times as likely to pay more than $100 for TKIs and 0.85 (95$100 for immunomodulatory drugs after parity. Conclusions: Among patients initiating TKIs or immunomodulatory drugs, parity was not associated with better adherence or less discontinuation of therapy but yielded decreased patient out-of-pocket payments for some patients