Undisclosed payments by pharmaceutical and medical device manufacturers to authors of endoscopy guidelines in the United States.

BACKGROUND AND AIMS: Payments from pharmaceutical and medical device manufacturers to authors of clinical practice guidelines (CPGs) may influence practice recommendations. It is therefore important to evaluate the completeness of financial conflict of interest (FCOI) declarations among CPG authors. METHODS: We performed a cross-sectional analysis of industry payments to authors of endoscopy guidelines published by 5 GI societies between 2014 and 2017. For each author we identified payments using the disclosure section of CPGs and the Centers for Medicare & Medicaid Services Open Payments (CMS-OP) database. We calculated the prevalence, monetary value, and type of declared and undeclared payments among authors. Payments were assessed for the calendar year of and before publication. RESULTS: Thirty-seven CPGs were included in the analysis comprising 569 author entries (91 unique individuals; 66.43% men, 92.6% physicians, 66.4% academically affiliated). Four hundred fifty-one episodes (79%) involved FCOIs, 451 (79%) had undisclosed FCOIs in the CMS-OP, and 445 (77%) had FCOIs relevant to a CPG recommendation. The median undisclosed payment value was $4807.26 (interquartile range, $334.84-$20,579.75). Male authors (odds ratio, 2.23; 95% confidence interval, 1.47-3.39) and academically affiliated authors (odds ratio, 8.87; 95% confidence interval, 5.57-14.13) were significantly more likely to have undeclared payments (P < .001). No CPGs met all National Academy of Medicine criteria. CONCLUSIONS: Recognizing concerns about the accuracy of the CMS-OP, there are substantial discrepancies between industry-reported payments and author self-disclosure. Additionally, there is a high prevalence of undisclosed payments by pharmaceutical and medical device manufacturers to these authors. Given the potential impact of these discrepancies and undisclosed payments on CPGs, more accurate reporting and alternative strategies for managing FCOI are needed.

Catalyst-Controlled Stereoselective Synthesis Secures the Structure of the Antimalarial Isocyanoterpene Pustulosaisonitrile-1.

Three new isocyanoditerpenes (5-7) have been characterized from Australian specimens of the nudibranch Phyllidiella pustulosa. The planar structure and (3R,6S,7R) absolute configuration of pustulosaisonitrile-1 were deduced by spectroscopic analyses at 900 MHz informed by molecular modeling, DFT calculations, and computational NMR chemical shift predictions and by comparison of experimental electronic circular dichroism (ECD) data with TDDFT-ECD calculations for the truncated model compound 8. A catalyst-controlled enantio- and diastereoselective total synthesis of the two most likely diastereomeric candidates for the structure of 5 solidified its (3R,6S,7R,10S,11R,14R) absolute configuration. Three individual enantioselective methods provided stereochemical control at key positions, permitting an unambiguous final structural assignment. Isocyanide 5 and synthetic diastereomers 5a and 5c showed activity against Plasmodium falciparum malaria parasites (IC50 ∼1 µM).