Personal Payments from Pharmaceutical Companies to Authors of Oncology Clinical Practice Guidelines.

BACKGROUND: Oncologists who author clinical practice guidelines frequently have financial relationships with the pharmaceutical industry. It is unknown whether participation on clinical practice guideline committees is associated with differences in the amounts of industry money received. MATERIALS AND METHODS: We conducted a nested case-control study from August 2013 to December 2018. We manually abstracted membership records of National Comprehensive Cancer Network (NCCN) Guidelines committees for the 20 most common cancers and linked to Open Payments. The study sample included medical oncologists selected to join an NCCN Guidelines committee ("joiners") during the study period. Joiners were matched 1:2 to medical oncologists who had no participation on NCCN committees (controls) by gender, NCCN institution, and medical school graduation year. We performed difference-in-differences (DiD) estimation to assess whether selection to an NCCN committee was associated with the dollar value of payments received from industry, using generalized estimating equations to address correlation between matched pairs and between repeated observations of the same pair. RESULTS: During the study period, 54 physicians joined an NCCN Guidelines committee. These physicians received more payments than matched controls in the year prior to joining ($11,259 vs. $3,427; p = .02); this difference did not increase in the year after joining (DiD = $731; p = .45). CONCLUSION: Medical oncologists selected to NCCN Guidelines committees had greater financial ties to industry than their peers. The potential influence of industry in oncology clinical practice guidelines may be reduced through the selection of committee members with fewer ties to industry. IMPLICATIONS FOR PRACTICE: Oncologists who author clinical practice guidelines frequently have financial conflicts of interest with the pharmaceutical industry. This creates concern about the potential for industry influence on guidelines. However, it is unknown whether oncologists who author guidelines have greater industry relationships than their peers. This study compared medical oncologists who were newly selected to join a National Comprehensive Cancer Network (NCCN) Guidelines panel with medical oncologists at the same institutions and at similar career stages. At the time they joined, oncologists joining NCCN Guidelines panels had received more than three times the dollar value of industry payments than their peers. The potential for industry influence may be reduced by the selection of less-conflicted panel members.

The Accuracy and Usefulness of the National Comprehensive Cancer Network Evidence Blocks Affordability Rating.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) Guidelines' Evidence Blocks has the broadest scope of the several oncology value assessment frameworks. The Evidence Blocks includes the Affordability criterion, which reflects the financial cost of each treatment on a 1-5 scale. The accuracy of Affordability is unknown. METHODS: We calculated Medicare costs for all first-line and maintenance treatments for the 30 cancers with the highest incidence in the USA that had published NCCN Evidence Blocks as of 31 December 2018. We assessed the accuracy and consistency of Affordability across different treatments and cancer types. Among different treatments for the same indication, we determined the frequency with which the Affordability assessment was consistent with calculated treatment costs. RESULTS: There were a total of 1386 treatments in our sample. Lower Affordability scores were associated with higher costs. There was significant variation in cost at each level of Affordability; for treatments with Affordability = 1 (very expensive), costs ranged from $US4551 to $US43,794 per month for treatments administered over an undefined time period and from $US2865 to $US500,982 per course of therapy for treatments administered over a defined time period. Among treatments for the same indication, Affordability was discrepant with calculated treatment costs in 7.9% of pairwise comparisons, identifying the higher-cost treatment as being more affordable. Discrepancies were reduced when we reassigned Affordability scores based on calculated treatment costs. CONCLUSIONS: Evidence Blocks Affordability generally correlated with treatment costs but contained discrepancies, which may limit its usefulness to clinicians in comparing costs. This study suggests that the Affordability score may be improved by indexing more directly to specified dollar value thresholds.

Use of High-Cost Cancer Treatments in Academic and Nonacademic Practice.

BACKGROUND: Academic physicians, such as those affiliated with National Cancer Institute (NCI)-designated Comprehensive Cancer Centers, may have different practice patterns regarding the use of high-cost cancer drugs than nonacademic physicians. MATERIALS AND METHODS: For this cohort study, we linked cancer registry, administrative, and demographic data for patients with newly diagnosed cancer in North Carolina from 2004 to 2011. We selected cancer types with multiple U.S. Food and Drug Administration-approved, National Comprehensive Cancer Network-recommended treatment options and large differences in reimbursement between higher-priced and lower-priced options (stage IV colorectal, stage IV lung, and stage II-IV head-and-neck cancers). We assessed whether provider's practice setting-NCI-designated Comprehensive Cancer Center ("NCI") versus other location ("non-NCI")-was associated with use of higher-cost treatment options. We used inverse probability of exposure weighting to control for patient characteristics. RESULTS: Of 800 eligible patients, 79.6% were treated in non-NCI settings. Patients treated in non-NCI settings were more likely to receive high-cost treatment than patients treated in NCI settings (36.0% vs. 23.2%), with an unadjusted prevalence difference of 12.7% (95% confidence interval [CI], 5.1%-20.0%). After controlling for potential confounding factors, non-NCI patients remained more likely to receive high-cost treatment, although the strength of association was attenuated (adjusted prevalence difference, 9.6%; 95% CI -0.1%-18.7%). Exploratory analyses suggested potential heterogeneity across cancer type and insurance status. CONCLUSION: Use of higher-cost cancer treatments may be more common in non-NCI than NCI settings. This may reflect differential implementation of clinical evidence, local practice variation, or possibly a response to the reimbursement incentives presented by chemotherapy billing. IMPLICATIONS FOR PRACTICE: Oncology care delivery and practice patterns may vary between care settings. By comparing otherwise similar patients treated in National Cancer Institute (NCI)-designated Comprehensive Cancer Centers with those treated elsewhere, this study suggests that patients may be more likely to receive treatment with certain expensive cancer drugs if treated in the non-NCI setting. These practice differences may result in differences in patient costs and outcomes as a result of where they receive treatment.

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.

Pharmaceutical assistance programs for cancer patients in the era of orally administered chemotherapeutics.

Introduction The rising cost of cancer drugs may make treatment unaffordable for some patients. Patients often rely on drug manufacturer-administered Pharmaceutical Assistance Programs (PAPs) to obtain drugs and reduced or no cost. The overall usage of PAPs within cancer care delivery is unknown. Methods We included all cancer patients across an academically affiliated, integrated health system in North Carolina during 2014 ( N = 8591). We identified the subset of patients receiving PAP assistance to afford one or more cancer drugs, in order to calculate the proportion of patients receiving PAP assistance, and the retail value of the assistance. Results Among 8591 cancer patients, 215 unique patients submitted a total of 478 successful PAP requests for cancer drugs. 40% of PAP-utilizing patients were uninsured, 23% had Medicaid coverage, 20% had Medicare coverage, 2% were dual Medicare/Medicaid eligible, and 14% were commercially insured. Among all cancer patients who received medical treatment, 6.0% required PAP assistance, whereas 10.6% receiving an oral agent required PAP assistance. The proportion receiving PAP assistance varied substantially by drug, ranging from <1% of patients (e.g. carboplatin, methotrexate) to 50% of patients (e.g. ponatinib, temsirolimus). The majority of the retail value obtained was for oral agents, including $1,556,575 of imatinib and $1,449,633 of dasatinib, which were the two drugs with the highest aggregate retail value. Conclusions A substantial proportion of cancer patients receive private charitable assistance to obtain standard-of-care treatments. This includes patients with federal and private insurance, suggesting an inability of patients to meet cost-sharing requirements.

Development of a Protease Biosensor Based on a Dimerization-Dependent Red Fluorescent Protein.

Dysregulated activity of the protease matriptase is a key contributor to aggressive tumor growth, cancer metastasis, and osteoarthritis. Methods for the detection and quantification of matriptase activity and inhibition would be useful tools. To address this need, we developed a matriptase-sensitive protein biosensor based on a dimerization-dependent red fluorescent protein (ddRFP) reporter system. In this platform, two adjoining protein domains, connected by a protease-labile linker, produce fluorescence when assembled and are nonfluorescent when the linker is cleaved by matriptase. A panel of ddRFP-based matriptase biosensor designs was created that contained different linker lengths between the protein domains. These constructs were characterized for linker-specific cleavage, matriptase activity, and matriptase selectivity; a biosensor containing a RSKLRVGGH linker (termed B4) was expressed at high yields and displayed both high catalytic efficiency and matriptase specificity. This biosensor detects matriptase inhibition by soluble and yeast cell surface expressed inhibitor domains with up to a 5-fold dynamic range and also detects matriptase activity expressed by human cancer cell lines. In addition to matriptase, we highlight a strategy that can be used to create effective biosensors for quantifying activity and inhibition of other proteases of interest.

Financial Relationships With Industry Among National Comprehensive Cancer Network Guideline Authors.

IMPORTANCE: Financial conflicts of interest (FCOIs) among authors of clinical practice guidelines have the potential to influence treatment recommendations. OBJECTIVE: To quantify FCOIs with industry among authors of the National Comprehensive Cancer Network (NCCN) guidelines. DESIGN, SETTING, AND PARTICIPANTS: We assessed FCOIs occurring during 2014 among NCCN guideline authors in the United States. All were physician members of the NCCN guideline committees for lung, breast, prostate, and colorectal cancer as of the end of 2014. The data source for FCOIs was Open Payments, which is publically reported by the Centers for Medicare and Medicaid Services. This study was cross-sectional. MAIN OUTCOMES AND MEASURES: The proportion of NCCN authors having FCOIs with industry; the average amount received from industry sources per author. RESULTS: Of 125 guideline authors, 108 (86%) had at least 1 reported FCOI. Authors received an average of $10 011 (range, $0-$106 859) in general payments (GPs), which include consulting, meals, lodging, and similar transfers of value, and $236 066 (range $0-$2 756 713) in industry research payments (RPs), including funding associated with clinical trials. Approximately 84% of authors received GPs, while 47% received RPs. Eight (6%) had FCOIs in excess of the $50 000 net and/or $20 000 single-company maximums stipulated by NCCN. CONCLUSIONS AND RELEVANCE: Among NCCN guideline authors, FCOIs involving RPs were of greater value, while those involving GPs were more prevalent. Although FCOIs may result from engaging in important scholarship, FCOIs may still influence guideline authors in counterproductive ways. Research is needed to understand how best to manage author FCOIs during guideline creation.

Clinical Trial Participants With Metastatic Renal Cell Carcinoma Differ From Patients Treated in Real-World Practice.

PURPOSE: Although narrow eligibility criteria improve the internal validity of clinical trials, they may result in differences between study populations and real-world patients, threatening generalizability. Therefore, we evaluated whether patients treated for metastatic renal cell cancer (mRCC) in routine clinical practice are similar to those enrolled onto clinical trials. PATIENTS AND METHODS: In this cohort study, we compared baseline characteristics of patients with mRCC in phase III clinical trials of new targeted therapies and those in a retrospective registry composed of academic (Duke) and community (ACORN Network) practices. RESULTS: A total of 438 registry patients received sunitinib, sorafenib, temsirolimus, or pazopanib (most commonly used agents) in first-line treatment. Registry patients receiving tyrosine kinase inhibitors (sunitinib, sorafenib, or pazopanib) were more likely to have poor-risk disease by Memorial Sloan Kettering Cancer Center criteria (poor, 7.4% v 2.9%; P < .001; favorable, 30.1% v 43.8%; P < .001) and to have impaired performance status (Eastern Cooperative Oncology Group > 1, 11.1% v 0.6%; P < .001). However, registry patients receiving temsirolimus were less likely to have poor-risk disease (poor, 10.2% v 69.4%; P < .001; favorable, 16.9% v 0%; P < .001). Thus, 39.0% of registry patients would have been excluded from the phase III clinical trial testing the drug they received. CONCLUSION: Patients with mRCC treated with tyrosine kinase inhibitors in real-world clinical practice are sicker than those enrolled onto pivotal clinical trials, and more than one third are trial ineligible. Application of clinical trial findings to dissimilar populations may result in patient harm. Clinical research with more inclusive eligibility criteria is needed to appropriately guide real-world practice.