Clinical research should ultimately improve patient care. For this to be possible, trials must evaluate outcomes that genuinely reflect real-world settings and concerns. However, many trials continue to measure and report outcomes that fall short of this clear requirement. We highlight problems with trial outcomes that make evidence difficult or impossible to interpret and that undermine the translation of research into practice and policy. These complex issues include the use of surrogate, composite and subjective endpoints; a failure to take account of patients’ perspectives when designing research outcomes; publication and other outcome reporting biases, including the under-reporting of adverse events; the reporting of relative measures at the expense of more informative absolute outcomes; misleading reporting; multiplicity of outcomes; and a lack of core outcome sets. Trial outcomes can be developed with patients in mind, however, and can be reported completely, transparently and competently. Clinicians, patients, researchers and those who pay for health services are entitled to demand reliable evidence demonstrating whether interventions improve patient-relevant clinical outcomes.

Background: We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset. Methods: We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up to 10 September 2020. We included studies attempting to culture or observe SARS-CoV-2 in specimens with RT-PCR positivity. Studies were dual-extracted and the data summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool. Results: We included 29 studies reporting attempts at culturing, or observing tissue infection by, SARS-CoV-2 in sputum, nasopharyngeal or oropharyngeal, urine, stool, blood, and environmental specimens. The quality of the studies was moderate with lack of standardized reporting. The data suggest a relationship between the time from onset of symptom to the timing of the specimen test, cycle threshold (Ct), and symptom severity. Twelve studies reported that Ct values were significantly lower and log copies higher in specimens producing live virus culture. Two studies reported that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >14 days, but infectious potential declined after day 8 even among cases with ongoing high viral loads. Four studies reported viral culture from stool specimens. Conclusions: Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs, and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high Ct are unlikely to have infectious potential.

Discrepancies between pre-specified and reported outcomes are an important source of bias in trials. Despite legislation, guidelines and public commitments on correct reporting from journals, outcome misreporting continues to be prevalent. We aimed to document the extent of misreporting, establish whether it was possible to publish correction letters on all misreported trials as they were published, and monitor responses from editors and trialists to understand why outcome misreporting persists despite public commitments to address it. We identified five high-impact journals endorsing Consolidated Standards of Reporting Trials (CONSORT) (New England Journal of Medicine, The Lancet, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine) and assessed all trials over a six-week period to identify every correctly and incorrectly reported outcome, comparing published reports against published protocols or registry entries, using CONSORT as the gold standard. A correction letter describing all discrepancies was submitted to the journal for all misreported trials, and detailed coding sheets were shared publicly. The proportion of letters published and delay to publication were assessed over 12 months of follow-up. Correspondence received from journals and authors was documented and themes were extracted. Sixty-seven trials were assessed in total. Outcome reporting was poor overall and there was wide variation between journals on pre-specified primary outcomes (mean 76% correctly reported, journal range 25–96%), secondary outcomes (mean 55%, range 31–72%), and number of undeclared additional outcomes per trial (mean 5.4, range 2.9–8.3). Fifty-eight trials had discrepancies requiring a correction letter (87%, journal range 67–100%). Twenty-three letters were published (40%) with extensive variation between journals (range 0–100%). Where letters were published, there were delays (median 99 days, range 0–257 days). Twenty-nine studies had a pre-trial protocol publicly available (43%, range 0–86%). Qualitative analysis demonstrated extensive misunderstandings among journal editors about correct outcome reporting and CONSORT. Some journals did not engage positively when provided correspondence that identified misreporting; we identified possible breaches of ethics and publishing guidelines. All five journals were listed as endorsing CONSORT, but all exhibited extensive breaches of this guidance, and most rejected correction letters documenting shortcomings. Readers are likely to be misled by this discrepancy. We discuss the advantages of prospective methodology research sharing all data openly and pro-actively in real time as feedback on critiqued studies. This is the first empirical study of major academic journals’ willingness to publish a cohort of comparable and objective correction letters on misreported high-impact studies. Suggested improvements include changes to correspondence processes at journals, alternatives for indexed post-publication peer review, changes to CONSORT’s mechanisms for enforcement, and novel strategies for research on methods and reporting.

Objectives: To identify and thematically analyse how healthcare professionals (HCPs) integrate patient values and preferences (‘values integration’) in primary care for adults with non-communicable diseases (NCDs).Design: Systematic review and meta-aggregation methods were used for extraction, synthesis and analysis of qualitative evidence.Data sources: Relevant records were sourced using keywords to search 12 databases (ASSIA, CINAHL, DARE, EMBASE, ERIC, Google Scholar, GreyLit, Ovid-MEDLINE, PsycINFO, PubMed-MEDLINE, Scopus and Web of Science).Eligibility criteria: Records needed to be published between 2000 and 2020 and report qualitative methods and findings in English involving HCP participants regarding primary care for adult patients.Data extraction and synthesis: Relevant data including participant quotations, authors’ observations, interpretations and conclusions were extracted, synthesised and analysed in a phased approach using a modified version of the Joanna Briggs Institute (JBI) Data Extraction Tool, as well as EPPI Reviewer and NVivo software. The JBI Critical Appraisal Checklist for Qualitative Research was used to assess methodological quality of included records.Results: Thirty-one records involving >1032 HCP participants and 1823 HCP-patient encounters were reviewed. Findings included 143 approaches to values integration in clinical care, thematically analysed and synthesised into four themes: (1)approaches of concern; (2)approaches of competence; (3)approaches of communicationand (4)approaches of congruence. Confidence in the quality of included records was deemed high.Conclusions: HCPs incorporate patient values and preferences in healthcare through a variety of approaches including showing concern for the patient as a person, demonstrating competence at managing diseases, communicating with patients as partners and tailoring, adjusting and balancing overall care. Themes in this review provide a novel framework for understanding and addressing values integration in clinical care and provide useful insights for policymakers, educators and practitioners.PROSPERO registration number: CRD42020166002.

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