Conflict of interest policies at Australian medical schools.

BACKGROUND: Pharmaceutical industry exposure is widespread during medical training and may affect education and clinical decision-making. Medical faculties' conflict of interest (COI) policies help to limit this exposure and protect students against commercial influence. AIMS: Our aim was to investigate the prevalence, content and strength of COI policies at Australian medical schools and changes since a previous assessment conducted in 2009. METHODS: We identified policies by searching medical school and host university websites in January 2021, and contacted deans to identify any missed policies. We applied a modified version of a scorecard developed in previous studies to examine the content of COI policies. All data were coded in duplicate. COI policies were rated on a scale from 0 (no policy) to 2 (strong policy) across 11 items per medical school. Oversight mechanisms and sanctions were also assessed, and current policies were compared with the 2009 study. RESULTS: Of 155 potentially relevant policies, 153 were university-wide and two were specific to medical schools. No policies covered sales representatives, on-site sponsored education or free samples. Oversight of consultancies had improved substantially, with 76% of schools requiring preapproval. Disclosure policies, while usually present, were weak, with no public disclosure required. CONCLUSION: We found little indication that Australian medical students are protected from commercial influence on medical education, and there has been limited COI policy development within the past decade. More attention is needed to ensure the independence of medical education in Australia.

The impact of feedback training on prediction of cancer clinical trial results.

INTRODUCTION: Funders must make difficult decisions about which squared treatments to prioritize for randomized trials. Earlier research suggests that experts have no ability to predict which treatments will vindicate their promise. We tested whether a brief training module could improve experts' trial predictions. METHODS: We randomized a sample of breast cancer and hematology-oncology experts to the presence or absence of a feedback training module where experts predicted outcomes for five recently completed randomized controlled trials and received feedback on accuracy. Experts then predicted primary outcome attainment for a sample of ongoing randomized controlled trials. Prediction skill was assessed by Brier scores, which measure the average deviation between their predictions and actual outcomes. Secondary outcomes were discrimination (ability to distinguish between positive and non-positive trials) and calibration (higher predictions reflecting higher probability of trials being positive). RESULTS: A total of 148 experts (46 for breast cancer, 54 for leukemia, and 48 for lymphoma) were randomized between May and December 2017 and included in the analysis (1217 forecasts for 25 trials). Feedback did not improve prediction skill (mean Brier score for control: 0.22, 95% confidence interval = 0.20-0.24 vs feedback arm: 0.21, 95% confidence interval = 0.20-0.23; p = 0.51). Control and feedback arms showed similar discrimination (area under the curve = 0.70 vs 0.73, p = 0.24) and calibration (calibration index = 0.01 vs 0.01, p = 0.81). However, experts in both arms offered predictions that were significantly more accurate than uninformative forecasts of 50% (Brier score = 0.25). DISCUSSION: A short training module did not improve predictions for cancer trial results. However, expert communities showed unexpected ability to anticipate positive trials.Pre-registration record: https://aspredicted.org/4ka6r.pdf.

How well are Phase 2 cancer trial publications supported by preclinical efficacy evidence?

Major ethics policies require that human studies be preceded by animal experiments. We probed the extent to which trials testing efficacy of cancer drugs cited preclinical efficacy studies testing the same drug and disease indication. Using a sample of Phase 2 trial publications for novel cancer monotherapies approved by Food and Drug Administration 2005-2007, we conducted a systematic analysis of citations to preclinical efficacy evidence within trial publications. Citations were classified based on whether they "matched" the drug and indication of the trial. Our sample included 179 Phase 2 publications published 2004-2016. At least one preclinical study was cited for 113 of 179 publications (63%); 56 (31%) cited matching preclinical studies, and 74 (41%) did not cite either matching preclinical or matching clinical trial evidence. When excluding evidence that would likely not have been available to investigators before trial launch, 45 trials (25%) cited matching preclinical studies; 91 (51%) did not cite any matched preclinical or clinical, preceding evidence. No relationship between citation of matching and preceding preclinical evidence and trial outcomes was observed (28.4% of nonpositive trials vs. 26.9% of positive trials, p ~ 1). This suggests that many Phase 2 trial publications do not cite matching preclinical efficacy studies. Limited citation either suggests its absence or its exclusion from a publication. To ensure trials rest on a sound ethical basis and that publications support valid inference, journal editors and referees might encourage more complete descriptions of preclinical evidence or, where appropriate, active disclosure of its absence.

Structural brain abnormalities in adolescents and young adults with congenital heart defect: a systematic review.

AIM: The primary objective of this systematic review is to define and quantify brain structural abnormalities present in adolescents and young adults with complex congenital heart defect (CHD). We also aim to evaluate the extent to which these structural abnormalities are associated with functional outcomes. METHOD: A search of studies examining brain structure by magnetic resonance imaging in adolescents and young adults with complex CHD was performed in Embase, MEDLINE, and Web of Science. A meta-analysis was conducted to determine the odds of brain abnormalities in young people with CHD. Results not included in the meta-analysis were collated using descriptive statistics. RESULTS: Two hundred and fifty-four studies were identified through the literature search. Among these, 14 original studies were included in the review. The odds of brain abnormalities in young people with CHD were 7.9 times higher (p<0.001) than in typically developing comparison individuals. Focal and multifocal lesions were the most common types of abnormality (odds ratio 22.5 [p<0.001]). Preliminary evidence from volumetric, cortical, and microstructural integrity measurements suggests that brain abnormalities are associated with poorer neurocognitive outcomes. INTERPRETATION: This review provides strong evidence that adolescents and young adults with CHD are at increased risk of presenting with structural brain abnormalities and highlights the contribution of advanced quantitative magnetic resonance imaging techniques to identify the subtle but frequent brain alterations in this population. However, more studies are needed to clarify how these abnormalities relate to function. WHAT THIS PAPER ADDS: There is a high prevalence of brain abnormalities in young people with congenital heart defect (CHD). Brain volumes, cortical measurements, and white matter microstructure are altered in young people with CHD. Brain abnormalities are associated with poorer function in young people with CHD.