Posttraumatic stress disorder and functional impairment among World Trade Center Health Registry enrollees 14-15 years after the September 11, 2001, terrorist attacks.

The September 11, 2001, terrorist attacks on the World Trade Center (WTC) in New York City (9/11) had health-related consequences, including posttraumatic stress disorder (PTSD). PTSD is associated with functional impairment, which varies by symptom severity and other factors. This study aimed to identify predictors of functional impairment in individuals with low versus high PTSD symptom severity levels. WTC Health Registry enrollees exposed to 9/11 were surveyed four times between 2003 and 2015; cumulated data for individuals who endorsed at least one symptom on the PTSD Checklist-Civilian Version (PCL-C) at Wave 4 (2015-2016) were included (N = 30,287) and examined cross-sectionally. Individuals were classified based on PCL-C scores as having low/no (2-29) or high levels of PTSD symptom severity (≥ 44). Functional impairment was defined as subsequent difficulties in daily living. Among low/no PTSD severity participants, adjusted odds ratios (aORs) for the associations between functional impairment and poor self-rated health (vs. good), low social support (vs. high), and no physical activity (vs. active) were 1.23-1.92. In the same group, low versus high household income was associated with more functional impairment, aOR = 1.34, 95% CI [1.13, 1.59]. Among participants with high-level PTSD symptoms, women, aOR = 1.70, 95% CI [1.31, 2.20], and Hispanic enrollees, aOR = 1.76, 95% CI [1.31, 2.36], were more likely to report an absence of impairment. Self-rated health, social support, and physical activity emerged as important predictors of PTSD-related functional impairment across PTSD symptom severity levels, supporting clinical interventions targeting these factors.

Physician Payments from Pharmaceutical Companies Related to Cancer Drugs.

BACKGROUND: Drug manufacturers claim that the purpose of financial payments to physicians is to facilitate education about new drugs. This claim suggests 2 testable hypotheses: payments should not be associated with drug revenue and payments for each drug should decline over time as physicians become educated. MATERIALS AND METHODS: We used open payments data on industry payments. We included payments for cancer drugs without generic/biosimilar competitors and used federal data sources to measure Medicare spending (a proxy for overall drug revenue) and a number of prescribers. We used generalized estimating equations (GEE) to model the drug-level association between industry payments and Medicare spending. Separately, we used GEE to estimate the change in payments with respect to the duration of time since initial FDA approval. RESULTS: The sample included 89 drugs and 361 drug-year observations. The total value of industry payments for oncology drugs increased, from $53 333 854 in 2014 to $90 343 731 in 2018. There was no association between log-transformed mean, per-physician industry payments, and per-physician Medicare spending (estimate -0.001, 95%CI, -0.005 to 0.004). Payments for individual drugs decreased over time; estimated payments in the subsequent year for a drug with mean, per-physician payments of $1000 in the index year was: $681* for drugs 0-4 years since approval, $825 for 5-9 years, and $679* for ≥10 years (*P < .05). CONCLUSIONS: Although industry-sponsored education may also serve marketing purposes, the absence of association between industry payments and Medicare spending and the decline in payments subsequent to approval are consistent with claims that industry payments function to facilitate physician education.

The Prescription Drug User Fee Act: Much More Than User Fees.

BACKGROUND: The Prescription Drug User Fee Act (PDUFA) is due for reauthorization in 2022. Beyond creating the user fee program which now generates a majority of the Food and Drug Administration (FDA) Human Drugs Program budget, PDUFA has made numerous additional changes to FDA policy during its 29-year history. FDA's budgetary dependence on user fees may advantage the industry in negotiating favorable policy changes through PDUFA. METHODS: The full texts of all prior PDUFA reauthorization bills and all submitted public comments and meeting minutes for the 2022 reauthorization were reviewed. Provisions affecting FDA regulatory authority and processes were identified. FINDINGS: PDUFA legislation has instituted a broad range of changes to FDA policy, including evidentiary standards for drug approval, accelerated pathways for approval, industry involvement in FDA decision-making, rules regarding industry information dissemination to providers, and market entry of generic drugs. Negotiations over the 2022 reauthorization suggest that industry priorities include increased application of real-world evidence, regulatory certainty, and increased communication between FDA and industry during the drug application process. CONCLUSIONS: The need for PDUFA reauthorization every 5 years has created a recurring legislative vehicle through which far-ranging changes to FDA have been enacted, reshaping the agency's interactions and relationship with the regulated industry. The majority of policy changes enacted through PDUFA legislation have favored industry through decreasing regulatory standards, shortening approval times, and increasing industry involvement in FDA decision-making. FDA's budgetary dependence on the industry, the urgency of each PDUFA reauthorization's passage to maintain uninterrupted funding, and the industry's required participation in PDUFA negotiations may advantage the industry.

Are Financial Payments From the Pharmaceutical Industry Associated With Physician Prescribing? : A Systematic Review.

BACKGROUND: Financial payments from the drug industry to U.S. physicians are common. Payments may influence physicians' clinical decision making and drug prescribing. PURPOSE: To evaluate whether receipt of payments from the drug industry is associated with physician prescribing practices. DATA SOURCES: MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science, and EconLit were searched without language restrictions. The search had no limiting start date and concluded on 16 September 2020. STUDY SELECTION: Studies that estimated the association between receipt of industry payments (exposure) and prescribing (outcome). DATA EXTRACTION: Pairs of reviewers extracted the primary analysis or analyses from each study and evaluated risk of bias (ROB). DATA SYNTHESIS: Thirty-six studies comprising 101 analyses were included. Most studies (n = 30) identified a positive association between payments and prescribing in all analyses; the remainder (n = 6) had a mix of positive and null findings. No study had only null findings. Of 101 individual analyses, 89 identified a positive association. Payments were associated with increased prescribing of the paying company's drug, increased prescribing costs, and increased prescribing of branded drugs. Nine studies assessed and found evidence of a temporal association; 25 assessed and found evidence of a dose-response relationship. LIMITATION: The design was observational, 21 of 36 studies had serious ROB, and publication bias was possible. CONCLUSION: The association between industry payments and physician prescribing was consistent across all studies that have evaluated this association. Findings regarding a temporal association and dose-response suggest a causal relationship. PRIMARY FUNDING SOURCE: National Cancer Institute.

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.

Increasing Financial Payments From Industry to Medical Oncologists in the United States, 2014-2017.

BACKGROUND: Personal payments from the pharmaceutical industry to US physicians are common and are associated with changes in physicians' clinical practice and interpretation of clinical trial results. We assessed temporal trends in industry payments to oncologists, with particular emphasis on payments to authors of oncology clinical practice guideline and on payments related to immunotherapy drugs. METHODS: We included US physicians with active National Plan and Provider Enumeration System records and demographic data available in the Centers for Medicare & Medicaid Services Physician Compare system who had a specialty type of medical oncology or general internal medicine. Medical oncologists serving on NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Panels were identified manually. Industry payments, and the subset associated with PD-1/PD-L1 drugs, were identified in Open Payments, the federal repository of all transactions of financial value from industry to physicians and teaching hospitals, from 2014 to 2017. RESULTS: There were 13,087 medical oncologists and 85,640 internists who received payments. The mean, annual, per-physician value of payments to oncologists increased from $3,811 in 2014 to $5,854 in 2017, and from $444 to $450 for internists; the median payment increased from $152 to $199 for oncologists and remained at $0 for internists. Oncologists who served on NCCN Guidelines Panels received a greater value in payments and experienced a greater relative increase: mean payments increased from $10,820 in 2014 to $18,977 in 2017, and median payments increased from $500 to $1,366. Among companies marketing PD-1/PD-L1 drugs, mean annual per-oncologist payments associated with PD-1/PD-L1 drugs increased from $28 to $773. Total per-oncologist payments from companies marketing PD-1/PD-L1 drugs experienced a 165% increase from 2014 to 2017, compared with a 31% increase among similar companies not marketing PD-1/PD-L1 drugs. CONCLUSIONS: Pharmaceutical industry payments increased for US oncologists from 2014 to 2017 more than for general internists. The increase was greater among oncologists contributing to clinical practice guidelines and among pharmaceutical companies marketing PD-1/PD-L1 drugs. The increasing flow of money from industry to US oncologists supports ongoing concern regarding commercial interests in guideline development and clinical decision-making.

Trends in financial payments from industry to US cancer centers, 2014-2021.

BACKGROUND: Industry payments to US cancer centers are poorly understood. METHODS: US National Cancer Institute (NCI)-designated comprehensive cancer centers were identified (n = 51). Industry payments to NCI-designated comprehensive cancer centers from 2014 to 2021 were obtained from Open Payments and National Institutes of Health (NIH) grant funding from NIH Research Portfolio Online Reporting Tools (RePORT). Given our focus on cancer centers, we measured the subset of industry payments related to cancer drugs specifically and the subset of NIH funding from the NCI. RESULTS: Despite a pandemic-related decline in 2020-2021, cancer-related industry payments to NCI-designated comprehensive cancer centers increased from $482 million in 2014 to $972 million in 2021. Over the same period, NCI research grant funding increased from $2 481  million to $2 724  million. The large majority of nonresearch payments were royalties and licensing payments. CONCLUSION: Industry payments to NCI-designated comprehensive cancer centers increased substantially more than NCI funding in recent years but were also more variable. These trends raise concerns regarding the influence and instability of industry payments.

Quality of Treatment Selection for Medicare Beneficiaries With Cancer.

PURPOSE: The Medicare part D Low-Income Subsidy (LIS) improves access to oral cancer drugs, but provides no assistance for clinician-administered/part B drugs. This analysis assessed the association between LIS participation and receipt of optimal cancer treatment. METHODS: We investigated initial systemic therapy using SEER-Medicare data (2015-2017) and National Comprehensive Cancer Network (NCCN) Evidence Blocks (EB) as the standard for treatment recommendations. We included cancer clinical scenarios wherein (1) ≥one treatment was optimal (higher efficacy and safety scores) versus other treatments; (2) identifiable in SEER-Medicare (eg, not defined by clinical data unavailable in registry data or claims); and (3) both EB and ASCO Value Framework agreed regarding optimal treatment. We fit logistic regression models to assess the association between receipt of systemic therapy (v no therapy) and patient and provider characteristics. Contingent on receipt of treatment, we modeled the likelihood of receiving a treatment ranked (by EB scores) within the highest or lowest quartile for that cancer type. RESULTS: Nine thousand two hundred and ninety patients were included across 11 clinical scenarios. Fifty-seven percent (5,336) of patients received any systemic therapy and 43% (3,954) received no systemic therapy. Compared with non-LIS participants, LIS participants were less likely to receive any systemic therapy versus no systemic therapy (odds ratio, 0.64 [95% CI, 0.57 to 0.72]). Contingent on receiving systemic therapy, LIS participants received treatment ranked within the worst quartile 24.8% of the time, compared with 21.9% of non-LIS patients (adjusted prevalence difference, 4.3% [95% CI, 0.5 to 8.2]). CONCLUSION: LIS participants were less likely to receive systemic therapy at all and were more likely to receive treatments that receive low NCCN EB scores.

Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection.

Lung cancer screening via annual low-dose computed tomography (LDCT) has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by an LDCT. Changes in genome-wide cell-free DNA (cfDNA) fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples, and then validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer, and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a five-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths.

Pharmaceutical industry payments and delivery of non-recommended and low value cancer drugs: population based cohort study.

OBJECTIVE: To estimate the association between oncologists' receipt of payments from the pharmaceutical industry and delivery of non-recommended or low value interventions among their patients. DESIGN: Cohort study. SETTING: Fee-for-service Medicare claims. PARTICIPANTS: Medicare beneficiaries with a diagnosis of incident cancer (new occurrence of a cancer diagnosis code in proximity to claims for cancer treatment, and no such diagnosis codes during a ≥1 year washout period) during 2014-19, who met additional requirements identifying them as at risk for one of four non-recommended or low value interventions: denosumab for castration sensitive prostate cancer, granulocyte colony stimulating factors (GCSF) for patients at low risk for neutropenic fever, nab-paclitaxel for cancers with no evidence of superiority over paclitaxel, and a branded drug in settings where a generic or biosimilar version was available. MAIN OUTCOME MEASURES: Receipt of the non-recommended or low value drug for which the patient was at risk. The primary association of interest was the assigned oncologist's receipt of any general payments from the manufacturer of the corresponding non-recommended or low value drug (measured in Open Payments) within 365 days before the patient's index cancer date. The two modeling approaches used were general linear model controlling for patients' characteristics and calendar year, and general linear model with physician level indicator variables. RESULTS: Oncologists were in receipt of industry payments for 2962 of 9799 patients (30.2%) at risk for non-recommended denosumab (median $63), 76 747 of 271 485 patients (28.3%) at risk for GCSF (median $60); 18 491 of 86 394 patients (21.4%) at risk for nab-paclitaxel (median $89), and 4170 of 13 386 patients (31.2%) at risk for branded drugs (median $156). The unadjusted proportion of patients who received non-recommended denosumab was 31.4% for those whose oncologist had not received payment and 49.5% for those whose oncologist had (prevalence difference 18.0%); the corresponding values for GCSF were 26.6% v 32.1% (5.5%), for nab-paclitaxel were 7.3% v 15.1% (7.8%), and for branded drugs were 88.3% v 83.5% (-4.8%). Controlling for patients' characteristics and calendar year, payments from industry were associated with increased use of denosumab (17.5% (95% confidence interval 15.3% to 19.7%)), GCSF (5.8% (5.4% to 6.1%)), and nab-paclitaxel (7.6% (7.1% to 8.1%)), but lower use of branded drugs (-4.6% (-5.8% to -3.3%)). In physician level indicator models, payments from industry were associated with increased use of denosumab (7.4% (2.5% to 12.2%)) and nab-paclitaxel (1.7% (0.9% to 2.5%)), but not with GCSF (0.4% (-0.3% to 1.1%)) or branded drugs (1.2% (-6.0 to 8.5%)). CONCLUSIONS: Within some clinical scenarios, industry payments to physicians are associated with non-recommended and low value drugs. These findings raise quality of care concerns about the financial relationships between physicians and industry.

Despite The FDA's Five-Year Plan, Black Patients Remain Inadequately Represented In Clinical Trials For Drugs.

For decades Black patients have been underrepresented in clinical trials of new treatments. In response, in 2015 the Food and Drug Administration (FDA) launched a five-year action plan aimed at improving diversity in and transparency of pivotal clinical trials for newly approved drugs. The plan contained many action steps that were aimed at improving the racial representativeness of clinical trials and enhancing the reporting of new drug side effects and benefits across diverse populations. Yet, relying on the FDA's Drug Trials Snapshots website, we failed to find evidence that the action plan improved representation of Black trial participants. Black patients remained inadequately represented in clinical trials for drugs, with a median of one-third the enrollment that would be required, whether the trials were started before, during, or after the action plan. Fewer than 20 percent of drugs had data regarding treatment benefits or side effects reported for Black patients; neither measure improved during the action plan period.

Assessment of Outcomes Associated With the Use of Newly Approved Oncology Drugs in Medicare Beneficiaries.

Importance: A lack of generalizability of pivotal cancer clinical trial data to treatment of older adults with Medicare could affect therapeutic decision-making in clinical practice. Objective: To evaluate the differences in survival, duration of therapy, and treatment patterns between clinical trial patients and older adults with Medicare receiving cancer drugs for metastatic solid cancers in usual practice. Design, Setting, and Participants: This retrospective cohort study, performed from May 1, 2018, to August 30, 2020, used the linked Surveillance, Epidemiology, and End Results (SEER) program and Medicare database to examine sequential US Food and Drug Administration (FDA)-approved cancer drug indications (2008-2013) for locally advanced or metastatic solid tumors to assess whether pivotal trials reflect the outcomes of Medicare patients with cancer treated in usual practice. Exposures: Treatment with FDA-approved cancer drugs for metastatic solid cancers in pivotal clinical trials and in the SEER-Medicare database. Main Outcomes and Measures: Overall survival, duration of treatment, and dose reductions among trial participants and treated Medicare patients. Results: A total of 11 828 trial participants (mean age, 61.8 years; 6718 [56.8%] male; and 7605 [64.3%] White) and 9178 SEER-Medicare patients (mean age, 72.7 years; 4800 [52.3%] male; and 7437 [81.0% White]) were compared. Twenty-nine indications for 22 cancer drugs were included. Median overall survival among Medicare patients was shorter than among patients in the clinical trial intervention arm for 28 of 29 indications (median difference, -6.3 months; range, -28.7 to 2.7 months). Median duration of therapy among Medicare patients was shorter for 23 of the 27 indications with data available (median difference, -1.9 months; range, -12.4 to 1.4 months). For 9 indications, there was information available regarding dose reductions in the package insert or trial publication. In all but 1 instance, dose reductions or single prescriptions were more common in the Medicare population compared with dose reductions among the clinical trial patients; for example, in the Medicare patients, 600 of 1032 (58.1%) received dose reduction or a single prescription and 172 of 1032 (16.7%) received a single prescription vs 734 of 3416 (21.5%) in the trial intervention arm. The exception was afatinib for non-small cell lung cancer: 34 of 71 (47.9%) received dose reduction or a single prescription and 15 of 71 (21.1%) received a single prescription among the Medicare patients vs 120 of 230 (52.2%) receiving dose reductions among the trial intervention group. Conclusions and Relevance: In this cohort study, patients receiving Medicare who were treated with FDA-approved cancer drugs did not live as long as treated clinical trial participants and commonly received treatment modifications. This study suggests that cancer clinical data relevant to newly approved drugs lack generalizability to Medicare beneficiaries with cancer; therefore, these agents should be used with caution.

Disparities in hepatitis A virus (HAV) vaccination coverage among adult travelers to intermediate or high-risk countries: The role of birthplace and race/ethnicity.

BACKGROUND: While the hepatitis A virus (HAV) vaccine is recommended for United States (US) travelers to endemic regions, vaccination rates are lower among non-US-born adults and some racial minority groups. PURPOSE: We aimed to examine the relationship between birthplace, race and their interaction as predictors of self-reported HAV vaccination among adult travelers to high-risk countries (HRCs) through analysis of the National Health Interview Survey (NHIS), 2012-2015. METHODS: The study included 36,872 US adult participants in the 2012-2015 NHIS who traveled to countries where HAV is endemic. The main outcome was self-reported HAV vaccination (≥2 doses). Complex survey methods were applied to all models to provide statistical estimates that were representative of US adults. Multivariable logistic regression models adjusting for demographic, socioeconomic, medical, and access-to-care characteristics were fitted to examine the association between birthplace, race, race-by-birthplace (for interaction) and vaccination status. RESULTS: For adult travelers to HRCs, the adjusted odds ratio (AOR) of HAV vaccination was lower for non-US-born compared to US-born adults, AOR 0.86 (95% CI; 0.76, 0.98). For Hispanics, the AOR of HAV vaccination was 0.80 (95% CI; 0.70, 0.91) as compared to non-Hispanic-Whites. Furthermore, a significant qualitative interaction between birthplace and race was found (P-value 0.0005). Among non-Hispanic Blacks, the adjusted odds of HAV vaccination for non-US-born adults were 1.35 (95% CI; 1.06, 1.72) times the odds for US-born adults. In contrast, the AORs of HAV vaccination of non-US-born versus US-born adults were 36% (95% CI; 17%, 51%) and 30% (95% CI; 12%, 44%), lower for Asians and Hispanics, respectively. CONCLUSIONS: The association between birthplace and HAV vaccination status differs by race among travelers to HRCs, with US-born non-Hispanic Black and non-US-born Asian and Hispanic adults having lower odds of vaccination. Health care resources should be focused on these target populations to improve travel vaccination compliance.