The phase 3 PROfound trial led to the recent approval of the PARP inhibitor olaparib for men with metastatic castration-resistant prostate cancer and mutations in homologous recombination repair genes. We raise methodological concerns about the trial, including: a suboptimal control arm, problematic use of crossover, use of radiographic progression-free survival as the primary endpoint, and ambiguous benefit for patients with mutations in homologous recombination repair genes other than BRCA1, BRCA2, and ATM.

Background

Many oncologists who lead guidelines and clinical trials have financial conflicts of interest (fCOI) with industry. However, the extent to which fCOI reaches all cancer care providers is not known. Here we describe industry payments across all cancer care specialties by specific drug.

Methods

This observational, retrospective cohort study used Open Payments to describe general payments (i.e. consulting fees, meals, travel) to all US physicians for any cancer medicine during 2016-2018. Endpoints included number and value of payments by specialty, drug, and year.

Results

During 2016-2018, industry made general payments to 52 441 physicians for 137 unique cancer drugs. Annual number of payments (465 655 in 2018) and total value ($98.5 million in 2018) increased over the study period (20 % and 31 % increase since 2016). Medical/hematologic oncologists, surgical oncologists and radiologists received the highest total value of payments, accounting for $65.7 million (67 % of total), $13.4 million (14 % of total) and $10.8 million (11 % of total) in 2018. In 2018, 5 % of physicians (n = 1660) received >$10 000 in annual payments and 0.6 % (n = 209) received >$100 000. Pembrolizumab and Nivolumab, were associated with the highest total payment in each year, accounting for 12 % and 6 % (2018) of total value, respectively.

Conclusions

While prior work has identified fCOIs among oncology leaders, these data suggest that payments extend across the cancer system.

Policy summary

Pre-existing data suggest a strong relationship between industry payments and physician prescribing. The current study demonstrates that fCOIs among oncology prescribers are pervasive. The oncology community must consider the extent to which these relationships influence clinical practice and regulatory policies.

Background

Over the past 2 decades there has been a substantial increase in the number of new cancer medicines; this has been accompanied by a dramatic rise in drug costs. It is unknown how these trends impact the revenue of the pharmaceutical sector.

Methods

Retrospective cohort study to characterize temporal trends of revenue generated from cancer medicines as a proportion of total drug revenue among 10 large pharmaceutical companies from 2010 to 2019. Itemized product-sales data publicly available through company websites or annual filings were used to identify annual drug revenue. Revenue data were adjusted for inflation and converted to 2019 US dollars.

Results

During the study period, cumulative annual revenue generated from cancer drugs increased by 70%: from $55.8 billion to $95.1 billion, while cumulative revenue from nononcology drugs decreased 18%: from $342.2 billion to $281.5 billion. The proportion of total drug revenue generated from oncology drugs increased substantially over the study period: from 14% in 2010 to 25% in 2019 (τ = 1.0, P < .001).

Conclusions

Among 10 of the world's largest pharmaceutical companies, revenues generated from the sale of cancer drugs have increased by 70% over the past decade, while revenues from other medicines have decreased by 18%. Revenues from cancer drugs now account for one-quarter of the net revenues from these companies. Further work is needed to understand if this increase in sales revenue reflects industry profit, and to what extent increased spending has translated into improvements in patient and population outcomes.

Importance

The randomized clinical trial (RCT) in oncology has evolved since its widespread adoption in the 1970s. In recent years, concerns have emerged regarding the use of putative surrogate end points, such as progression-free survival (PFS), and marginal effect sizes.

Objective

To describe contemporary trends in oncology RCTs and compare these findings with earlier eras of RCT design and output.

Design, setting, and participants

Retrospective cohort study of systemic therapy RCTs in breast, colorectal, and non-small cell lung cancer published in 7 major journals between 2010 and 2020. This strategy replicates prior work and allows for comparison of trends with RCTs published between 1995 to 2004 and 2005 to 2009.

Main outcomes and measures

Data on RCT design, funding, results, and reporting were extracted from the published RCT report. Findings from the current period (2010-2020) were compared with data from RCTs published from 1995 to 2004 and 2005 to 2009. Descriptive and bivariate statistics were used to analyze temporal trends.

Results

The cohort included 298 RCTs (132 [44%] breast, 111 [37%] non-small cell lung cancer, 55 [19%] colorectal cancer). Experimental treatment included molecular inhibitor (171 of 298 [57%]), cytotoxic (83 of 298 [28%]), hormone (15 of 298 [5%]), and immune (24 of 298 [8%]) therapies. Sixty-nine percent (206 of 298) of RCTs were of palliative intent. The most common primary end point is now PFS; this has increased substantially over time (from 0% [0 of 167] to 18% [25 of 137] to 42% [125 of 298]; P < .001). Of 298 RCTs, 265 (89%) are now funded by industry (previously 95 of 167 [57%] and 107 of 137 [78%]; P < .001). Fifty-eight percent (173 of 298) of trials met their primary end point. Among positive trials, median improvement in overall survival and PFS was 3.4 and 2.9 months, respectively. More than one-third (117 of 298 [39%]) of reports used a professional medical writer; this increased substantially during the study period (from 3 of 27 [11%] in 2010 to 12 of 18 [67%] in 2020; P < .001).

Conclusions and relevance

This cohort study suggests that contemporary oncology RCTs now largely measure putative surrogate end points and are almost exclusively funded by the pharmaceutical industry. The increasing role of medical writers warrants attention. To demonstrate that new cancer treatments are high value, the oncology community needs to consider the extent to which study end points and target effect size provide meaningful benefit to patients.

Purpose

Many oncologists have relationships with industry. Previous work has shown that these payments are usually modest; however, there exist a subset of medical oncologists who receive more than $100,000 US dollars (USD) annually. Here, we describe the characteristics of these physicians.

Methods

This retrospective cohort study used the Open Payments data set to identify all US-based medical oncologists/hematologists who received $100,000+ USD in general payments linked to cancer medications in 2018. Open Payments and a web-based search were used to identify physician characteristics, demographics, research profile, and leadership positions.

Results

One hundred thirty-nine medical oncologists received > $100,000 USD in general payments. The median payment was $154,613 USD, and the total payment was $24.2 million USD. These high-payment physicians represent 1% of all US medical oncologists (N = 10,620) yet account for 37% of all industry payments in 2018. Sixty percent (84 of 139) and 21% (29 of 139) of these high-payment physicians hold hospital and specialty association leadership roles, respectively. One quarter (24%, 33 of 139) serve on journal editorial boards, and 10% (14 of 139) have authored clinical practice guidelines; 72% (100 of 139) hold faculty appointments.

Conclusion

A small number of medical oncologists receive very high payments from the pharmaceutical industry. These physicians hold major leadership roles within oncology. Further work is needed to understand the extent to which these conflicts of interest may shape clinical practice and policy.

Introduction

Oncology media websites such as Oncology Live (OncLive) and Targeted Oncology (TargetedOnc) play an important role in the dissemination of oncology news to patients and clinicians; however, the quality of the content on these websites has not been assessed. Our study aimed to analyze content from these websites and assess financial conflicts of interest (FCOI) amongst speakers interviewed on these websites.

Methods

Articles published on OncLive and TargetedOnc during October 2021, were prospectively captured and analyzed. The primary outcome of our study was the quality of oncology news reporting in OncLive and TargetedOnc. We assessed the FCOI amongst speakers using data from Open Payments.

Results

We examined 196 articles (OncLive 108, TargetedOnc 88). Limitations of cited research were reported in 7% (7/105) of OncLive and zero TargetedOnc articles. Benefit and risks in absolute numbers were reported in 28% (28/99) of OncLive and 16% (7/45) of TargetedOnc articles. Independent experts were quoted in 47% (51/108) and 51% (44/86) of the OncLive and TargetedOnc articles, respectively (Table 3). Pharmaceutical executives were quoted in 18% (20/108) and 11% (10/88) of OncLive and TargetedOnc articles, respectively. No FCOI disclosures were listed or reported for any articles. The mean general payment received from industry by United States physicians was $63,861 in 2019 and $39,639 in 2020.

Conclusion

Our study demonstrates low quality and potentially biased reporting of oncology news on OncLive and TargetedOnc. Careful safeguards, oversight and reporting of relevant FCOI are needed to maintain the quality and transparency of content being provided.