Financial conflicts of interest of physicians followed by oncology journals on Twitter.

BACKGROUND: Physicians have increasingly adopted Twitter as a discussion and distribution platform for oncology research. While the influence of financial conflicts of interests (FCOI) on medical research is well documented, their role in the dissemination of research on social media platforms is not well known. In this study, we sought to evaluate the FCOIs of physicians followed by the top three oncology journals on Twitter. MATERIALS AND METHODS: We used the Open Payments Search Tool ( https://openpaymentsdata.cms.gov ) to assess FCOIs between 2016 and 2021 of United States (US) physicians followed by three oncology journals (Journal of Clinical Oncology, The Lancet Oncology, and Annals of Oncology) on Twitter. RESULTS: Of 1914 Twitter accounts followed by the top three oncology journals on Twitter, 547 (28.6%) belonged to US physicians. Of these, 463 (84.6%) received general payments between 2016 and 2021. After excluding 30 US physicians currently in residency or fellowship, this percentage increased to 88.2% (n = 456/517). Combined, the median (interquartile range) general payment amount was $8100 ($200-90,000). Additionally, over $42 million in general payments were made between 2016 and 2021. CONCLUSION: Our findings offer insight on FCOIs between oncology journals and US physicians on Twitter. These findings may serve as the foundation for future research regarding optimal medical journal conduct on social media platforms.

Financial conflicts of interest of physicians followed by neurosurgical journals on Twitter.

BACKGROUND: Social media, particularly Twitter, has played an increasing role in networking and the dissemination of neurosurgical research. Despite extensive study on financial conflicts of interest (FCOI) influencing medical research, little is known about the function of conflicts of interest on social media and the influence they may have. In this study, we sought to evaluate the FCOI of physicians followed on Twitter by the top three neurosurgical journals. MATERIALS AND METHODS: We analysed the FCOI of United States (US) physicians followed by the top three neurosurgical journals (Journal of Neurosurgery, World Neurosurgery, Neurosurgery) on Twitter. We determined the FCOIs of each physician using the Open Payments Search Tool located at https://openpaymentsdata.cms.gov and summed the data between 2014 and 2021. RESULTS: We examined 2651 Twitter accounts followed by the top three neurosurgical journals on Twitter and determined 705 (26.6%) belonged to US physicians. Of the 705 US physicians, 577 (81.8%) received general payments between 2014 and 2021. After excluding US physicians currently in residency or fellowship (n = 157), this percentage increased to 93.2% (n = 511/548). In total, nearly $70 million in general payments were made between 2014 and 2021. CONCLUSION: These findings raise questions regarding the interaction between neurosurgical journals and the medical community on Twitter. This study may serve as the basis for future work on best practices for medical journals navigating their affiliations on Twitter.

Eventual success rate and predictors of success for oncology drugs tested in phase I trials.

Previous estimates of the likelihood of a drug tested in phase I trials obtaining FDA clearance are out of date. In the intervening years, newer pharmaceuticals have been developed, resulting in new delivery systems and lines of therapies. We sought to explore and update these estimates by comprehensively searching drugs tested in phase I trials and to determine the factors associated with later receiving FDA approval. In a cross-sectional analysis, we searched for anti-tumor drugs tested in phase I trials and published in scientific journals or presented at hematology/oncology conferences. For each drug, we searched PubMed for phase II and phase III studies testing the drug for the same indication tested in phase I studies. We found 51 drug approvals; four were withdrawn. The probability of a drug tested in 2015 being approved by 2021 was 6.2%. Drugs tested as monotherapy were more likely to receive approval than drugs tested in combination, and monoclonal antibodies were more likely to receive approval than drugs of other mechanisms. In adjusted models, response rates higher than 40% in phase I studies, demonstrating an improvement in overall survival (OS) in phase III studies, and drugs tested as monotherapy were associated with receiving FDA approval. When looking at all drugs tested during a single year, most drugs were not approved, and among those that are approved, almost 8% are withdrawn. Response rates higher than 40%, testing a drug as monotherapy, and demonstrating an improvement in OS were associated with receiving FDA approval.

Relugolix: Five Reasons Why the US Food and Drug Administration Should Have Exercised Restraint.

We highlight concerns regarding the approval of relugolix for patients with prostate cancer. These include the unsuitable comparator arm and primary endpoint in the HERO trial, as well as potential selection bias and the poor representativeness of the trial population. Dosing adherence to a daily tablet may also be an issue in comparison to injections at 3-mo intervals. Rigorous postmarketing trials of relugolix assessing clinically meaningful endpoints for these patients are needed.

Lutetium-177-PSMA-617 in Metastatic Castration-resistant Prostate Cancer: Limitations of the VISION Trial.

Lu-PSMA was approved in the USA for patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer already treated with androgen receptor pathway inhibition and taxane-based chemotherapy on the basis of results from VISION. Three limitations affected the control arm in VISION: choice of the standard of care was limited, some patients initially deemed ineligible for taxane later received it, and there was a high attrition rate. VISION is an example of the many challenges in modern oncology trials. The direct and indirect costs of Lu-PSMA also mean that this therapy is likely to be out of reach for many nations, deepening global inequities in health care access.

A novel trial methodology to test interventions with very large effect sizes: the case of dostarlimab in mismatch repair-deficient, locally advanced rectal cancer.

Dostarlimab (Jemperli, GlaxoSmithKline) is an anti-programmed death receptor-1 monoclonal antibody (anti-PD-1) recently tested in a non-randomized, phase II trial (NCT04165772) which included patients with mismatch repair-deficient, locally advanced rectal cancer. Among the first 12 patients treated with dostarlimab, 100% achieved a clinical complete response with no patients experiencing progression or recurrence to date. Most impressive, none required chemotherapy, radiotherapy or surgery the prevailing standard of care. In this paper, we discuss the impressive results of this trial and how they relate to cancer policy, as well as propose a novel trial methodology to assess dostarlimab.

Financial conflicts of interest of OncoAlert: An informal oncology professional network.

IMPORTANCE: Social media platforms have allowed the formation of informal professional healthcare networks. Transparency in funding, membership requirements, financial conflicts of interest (FCOI), and messaging are necessary to ensure best practices for similar networks in the future. OBJECTIVE: To analyze the FCOIs of US-based physician members of the OncoAlert Network and appraise the content of their public Twitter account. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study assessed the FCOIs among US-based physician members of the OncoAlert Network between 2015 and 2020. FCOI data were obtained through the Open Payments Database. Additionally, tweets were examined for content analysis. MAIN OUTCOMES AND MEASURES: The number of US-based physician members with FCOIs with the pharmaceutical industry; the amount of general, research, and associated research payments; and the perceived attitude of tweet content from the OncoAlert Network Twitter account. RESULTS: Of 34 US physician members of the OncoAlert Network, 31 (91.2%) received general payments from pharmaceutical companies according to the Open Payments Database. Between 2015 and 2020, US physician members of the OncoAlert Network received a median of $83,600 in general payments (interquartile range [IRQ], $7,200-$221,500). Fourteen members (41.1%) received more than $100,000 in general payments. Additionally, 480 (15.7 %) of 3064 tweets retrieved from the OncoAlert Twitter account mentioned a drug or clinical trial. Of these, 31.6 % (n = 152) had a positive disposition and 3.3 % (n = 16) were negative or critical. CONCLUSIONS AND RELEVANCE: Over 90% of US physician members of the OncoAlert Network had FCOIs between 2015 and 2020. Despite the network's non-profit status, FCOIs amongst its members may influence content produced on the network's social media platforms, such as Twitter, where content discussing drugs and clinical trials are often positive and seldom negative or critical. For future informal professional networks, further research is required to establish best practices for issues such as membership requirements, funding, and FCOI disclosure.

The AGILE trial of ivosidenib plus azacitidine versus azacitidine alone: How many limitations is too many?

The AGILE trial compared ivosidenib and azacitidine versus azacitidine for IDH1-mutant acute myeloid leukemia (AML) in elderly patients who were ineligible to receive intensive chemotherapy. While the results of this trial appear encouraging, various concerns become evident from the study design and methodology. First, the AGILE trial did not use post-protocol therapy that met the current standard of care. Second, researchers continued patient enrollment despite knowledge of the survival benefit of azacitidine plus venetoclax shown in the VIALE-A trial, resulting in an inferior control arm. Third, the primary endpoint of AGILE was changed from overall survival (OS) to event-free survival (EFS), and the sample size was reduced to expedite the results. Finally, the trial was halted early based on a non-primary endpoint, which likely led to exaggerated effect size or misleading results. We discuss these limitations and continue to advocate for careful analysis of study design to ensure that appropriate and accurate outcomes are implemented in future studies.

Common misconceptions of randomized controlled trials in oncology.

In biomedicine, randomized controlled trials are regarded as the gold standard of evidence owing to their ability to minimize confounding factors that may influence results. Randomized trials that are properly designed serve as a basis for drug regulation and national guideline development. Despite the many advantages of the study design, there are several misconceptions regarding randomized trials, particularly in oncology. These misconceptions include: the difficulty of designing and conducting a trial, the length of time necessary to complete a trial, the expense, appraisal and critique, pharmaceutical industry influence, and ethical standards. Furthermore, developing regulatory and strategic frameworks has the potential to enhance the randomized trial landscape. Such initiatives will focus on relevant clinical issues that persist in oncology, reducing duplicative and unethical trials and maximizing value-based healthcare. Here, we address several misconceptions regarding randomized controlled trials and provide potential solutions to enhance their methodology and implementation.

Characteristics of oncology podcasts: Attitudes, speakers, conflicts.

OBJECTIVE: To systematically appraise the content within oncology podcasts and the individuals who speak on them. DESIGN: A cross-sectional study. SETTING: We obtained a list of 33 current podcasts with substantial oncologic content through queries of predetermined search terms on the Apple Podcast Platform. PARTICIPANTS: 98 oncology-related podcast episodes. MAIN OUTCOMES: The perceived attitude of the episode with predetermined categories including "Neutral," "Favorable," or "Negative," the number of conflicts of interest verbally disclosed by individuals featured on oncology podcasts, and the prevalence of general payments among featured physicians. RESULTS: Among 33 oncology podcasts, the median number of episodes was 81 (IQR: 25-129). Ninety-seven percent (n = 32/33) of the podcasts included guests. The median episode run time was 26:50 min (IQR: 18:00 - 41:75). Among the 98 episodes assessed, 47% of episodes (n = 46/98) mentioned oncologic drugs, of which 57% (n = 26) had a neutral disposition, 37% (n = 17) had a favorable disposition and 7% (n = 3) were negative. Across 98 episodes, we identified 194 featured individuals, of which 65% (n = 126) had a medical degree (MD), and 85% (n = 107/126) of these physicians received at least one general payment. Further, 83% (n = 105/126) of physicians did not disclose payments. CONCLUSIONS AND POLICY SUMMARY: Within oncology-related podcasts, the majority of conversations about oncologic drugs are perceived as either favorable or neutral, and a majority of individuals featured on podcasts do not disclose conflicts of interest, highlighting potential opportunities for improvement, including the need for standardization of financial conflict of interest disclosure.

How Often do Medical Specialties Question the Practices that They Perform? An Empirical, Cross-Sectional Analysis of the Published Literature.

An aspect of overuse is who decides which practices are evaluated for overuse and which of the studies on overuse are published in the medical literature. We sought to examine the frequency with which studies in medical journals questioned an established practice. As a secondary objective, we sought to determine if there was variance among medical specialties. We conducted a retrospective, cross-sectional review of the published literature in 14 medical specialty journals. We included studies from one issue in three high-impact journals (November/December 2020) for each specialty. We assessed whether the study reported on a medical practice, whether it reported on an existing practice, whether the author expressed uncertainty regarding the practice, whether the study was a randomized design, and if the authors encouraged further testing in randomized studies. For all medical specialties combined, we found that 37% (n = 98) questioned existing practices, and 15% (n = 40) either tested the practice in a randomized trial or encouraged future randomized testing of the practice. The medical specialties that questioned their practices the most were gastroenterology (61%; n = 10/18), obstetrics/gynecology (52%; n = 11/21), and cardiovascular (50%; n = 5/10). These findings indicate that, although research is being conducted to examine current medical practices, few studies advocate for randomized testing of these practices, and even fewer actually test them in a randomized fashion. Additionally, the variation across medical specialties suggests areas in which to look for potential practices that are low-value, duplicative, and/or wasteful.

Concerning FDA approval of trilaciclib (Cosela) in extensive-stage small-cell lung cancer.

Trilaciclib is a recently approved cyclin-dependent kinase 4/6 inhibitor that is designed to decrease the incidence of chemotherapy-induced myelosuppression in adult patients with extensive-stage small-cell lung cancer receiving chemotherapy. Currently, this first-in-class therapy raises two open issues: its bio-plausibility and paucity of evidence demonstrating a lasting impact on clinical endpoints. Based on the existing phase 2 data, trilaciclib appears to be a therapy that can make a positive impact by preventing myelosuppression, but empirical validation with larger phase III trials should be conducted to confirm these benefits. The purpose of this article is to facilitate discussion about the role of trilaciclib in clinical practice and the need for additional trials.