The detection and management of attempted fraud during an online randomised trial.

BACKGROUND: Online studies offer an efficient method of recruiting participants and collecting data. Whilst delivering an online randomised trial, we detected unusual recruitment activity. We describe our approach to detecting and managing suspected fraud and share lessons for researchers. METHODS: Our trial investigated the single and combined effects of different ways of presenting clinical audit and feedback. Clinicians and managers who received feedback from one of five United Kingdom national clinical audit programmes were emailed invitations that contained a link to the trial website. After providing consent and selecting their relevant audit, participants were randomised automatically to different feedback versions. Immediately after viewing their assigned feedback, participants completed a questionnaire and could request a financial voucher by entering an email address. Email addresses were not linked to trial data to preserve participant anonymity. We actively monitored participant numbers, questionnaire completions, and voucher claims. RESULTS: Following a rapid increase in trial participation, we identified 268 new voucher claims from three email addresses that we had reason to believe were linked. Further scrutiny revealed duplicate trial completions and voucher requests from 24 email addresses. We immediately suspended the trial, improved security measures, and went on to successfully complete the study. We found a peak in questionnaires completed in less than 20 seconds during a likely contamination period. Given that study and personal data were not linked, we could not directly identify the trial data from the 268 duplicate entries within the 603 randomisations occurring during the same period. We therefore excluded all 603 randomisations from the primary analysis, which was consequently based on 638 randomisations. A sensitivity analysis, including all 961 randomisations over the entire study except for questionnaire completions of less than 20 seconds, found only minor differences from the primary analysis. CONCLUSION: Online studies offering incentives for participation are at risk of attempted fraud. Systematic monitoring and analysis can help detect such activity. Measures to protect study integrity include linking participant identifiers to study data, balancing study security and ease of participation, and safeguarding the allocation of participant incentives. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN41584028. Registration date is August 17, 2017.

A randomised fractional factorial screening experiment to predict effective features of audit and feedback.

BACKGROUND: Audit and feedback aims to improve patient care by comparing healthcare performance against explicit standards. It is used to monitor and improve patient care, including through National Clinical Audit (NCA) programmes in the UK. Variability in effectiveness of audit and feedback is attributed to intervention design; separate randomised trials to address multiple questions about how to optimise effectiveness would be inefficient. We evaluated different feedback modifications to identify leading candidates for further "real-world" evaluation. METHODS: Using an online fractional factorial screening experiment, we randomised recipients of feedback from five UK NCAs to different combinations of six feedback modifications applied within an audit report excerpt: use effective comparators, provide multimodal feedback, recommend specific actions, provide optional detail, incorporate the patient voice, and minimise cognitive load. Outcomes, assessed immediately after exposure to the online modifications, included intention to enact audit standards (primary outcome, ranked on a scale of -3 to +3, tailored to the NCA), comprehension, user experience, and engagement. RESULTS: We randomised 1241 participants (clinicians, managers, and audit staff) between April and October 2019. Inappropriate repeated participant completion occurred; we conservatively excluded participant entries during the relevant period, leaving a primary analysis population of 638 (51.4%) participants. None of the six feedback modifications had an independent effect on intention across the five NCAs. We observed both synergistic and antagonistic effects across outcomes when modifications were combined; the specific NCA and whether recipients had a clinical role had dominant influences on outcome, and there was an antagonistic interaction between multimodal feedback and optional detail. Among clinical participants, predicted intention ranged from 1.22 (95% confidence interval 0.72, 1.72) for the least effective combination in which multimodal feedback, optional detail, and reduced cognitive load were applied within the audit report, up to 2.40 (95% CI 1.88, 2.93) for the most effective combination including multimodal feedback, specific actions, patient voice, and reduced cognitive load. CONCLUSION: Potentially important synergistic and antagonistic effects were identified across combinations of feedback modifications, audit programmes, and recipients, suggesting that feedback designers must explicitly consider how different features of feedback may interact to achieve (or undermine) the desired effects. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN41584028.

Female sex is strongly associated with cognitive impairment in HIV infection.

BACKGROUND: Neurocognitive disorders remain frequent despite highly active antiretroviral treatment (HAART). The CNS is known as the sanctuary of HIV infection, where persistent neuroinflammation occurs regardless of viral suppression. Moreover, opportunistic infections, neurovascular damage and HAART neurotoxicity contribute to neurocognitive impairment. Therefore, detailed epidemiological studies might help to elucidate those complex mechanisms. OBJECTIVE: To investigate the prevalence of cognitive impairment and the associated sociodemographic, clinical and neuropsychological variables among HIV-infected patients admitted to a tertiary centre, in southern Brazil. METHODS: An observational, cross-sectional and analytic study was conducted between February 2019 and March 2020, in Hospital Nereu Ramos (HNR), with148 HIV-infected patients. They were interviewed, submitted to the International HIV Dementia Scale (IHDS) and had their medical data analysed. RESULTS: The prevalence of cognitive impairment was 69.6%. It was higher among women (OR = 3.5; 95% CI 1.5-8; p < 0.01), independently of depression, educational status and age. Full years of schooling were strongly associated with IHDS scores (p < 0.01). Patient Health Questionnaire-9 (PHQ-9) scores for depression (p = 0.8), time since HIV diagnosis (p = 0.2), CD4+ cell counts (p = 0.8) and viral load (p = 0.8) were not associated with IHDS scale. CONCLUSION: A high prevalence of cognitive impairment in HIV-infected patients was identified, independently associated with the female sex and fewer years of schooling. Further studies are needed to clarify the differences in the pathophysiology between sexes and the role of cognitive reserve in prevention of cognitive impairment in HIV infection.