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Introduction Statins reduce the incidence of cardiovascular disease (CVD) and cause few adverse effects. Half of patients prescribed statins discontinue treatment due to perceived intolerance. Placebo-controlled (blinded) n-of-1 trials have shown people with perceived intolerance that the statin does not cause adverse events and most resume treatment. However, blinded n-of-1 trials are impractical to deliver in routine practice. Tackling Statin Intolerance using n-of-1 trials (TaSINI) will test the feasibility of a general practitioner (GP)-delivered behavioural intervention endorsing an unblinded n-of-1 trial to increase adherence to statins relative to usual care. Methods and analysis TaSINI is a feasibility randomised controlled trial with a nested qualitative substudy. Ninety primary care patients who have discontinued statins due to intolerance or refused treatment will be randomised to an unblinded n-of-1 trial, a blinded n-of-1 trial (positive control) or usual care (negative control). Participants randomised to usual care will be advised to take statin therapy to prevent CVD. In both n-of-1 trial arms, GPs will deliver a behaviourally informed intervention that accessibly explains the benefits of statins, the prevalence of adverse effects and endorse the benefit of experimenting with medication. Participants will alternate between 4 weeks of medication and no medication (unblinded arm) or randomly sorted active and placebo (blinded arm) and will record adherence, symptoms and symptom attributions throughout. After 6 months, GPs will feedback symptom data during active/inactive treatment periods. All participants will be asked if they would like to initiate statin treatment. Measures of feasibility will be met if 4% of invited patients enrol, 50% of participants randomised to n-of-1 trials engage with the experiment and 25% more participants initiate statin in the unblinded n-of-1 arm than in usual care. Ethics and dissemination This study has been granted ethical approval by North of Scotland Research Ethics Service. The results will be written up for publication and show whether to progress to an effectiveness trial where the primary outcome would be differences in low-density lipoprotein concentration. [ABSTRACT FROM AUTHOR]

The revised Declaration of Helsinki allows placebo-controlled trials to be used even when there is an established therapy, provided there are adequate 'methodological' reasons for doing so. This seems to violate the principle of beneficence: where there is an established therapy, physicians treating patients with a placebo are withholding a known effective therapy. Because of this problem, we hypothesised that clinical researchers may be unwilling to risk violating the principle of beneficence and employ placebo-controlled trials in cases where there is an established therapy. In this paper, we began to investigate this hypothesis. After summarising the arguments for and against using placebo controls in clinical practice, we exploredthe extent to which placebo-controlled trials are used in cases where there is an established therapy. To do this, we conducted as systematic search for all placebo-controlled trials published in 2015 in the five highest impact general medical journals. We identified 70 placebo-controlled trials. Of these, 66 were for indications where there was no established effective therapy. Only four used a placebo control in spite of there being an available effective therapy. The infrequent use of placebo controlled trials where established therapy exists highlights a seeming discrepancy between what the Declaration of Helsinki allows and what clinical investigators believe to be ethically acceptable. The evidence presented in this paper suggests that the Declaration of Helsinki be reconsidered, and perhaps revised, in light of actual practice. [ABSTRACT FROM AUTHOR]

Objective: Despite the growing number of point-ofcare (POC) tests available, little research has assessed primary care clinician need for such tests. We therefore aimed to determine which POC tests they actually use or would like to use (if not currently available in their practice). Design: Cross-sectional survey. Setting: Primary care in Australia, Belgium (Flanders region only), the Netherlands, the UK and the USA. Participants: Primary care doctors (general practitioners, family physicians). Main measures: We asked respondents to (1) identify conditions for which a POC test could help inform diagnosis, (2) from a list of tests provided: evaluate which POC tests they currently use (and how frequently) and (3) determine which tests (from that same list) they would like to use in the future (and how frequently). Results: 2770 primary care clinicians across five countries responded. Respondents in all countries wanted POC tests to help them diagnose acute conditions (infections, acute cardiac disease, pulmonary embolism/deep vein thrombosis), and some chronic conditions (diabetes, anaemia). Based on the list of POC tests provided, the most common tests currently used were: urine pregnancy, urine leucocytes or nitrite and blood glucose. The most commonly reported tests respondents expressed a wish to use in the future were: D-dimer, troponin and chlamydia. The UK and the USA reported a higher actual and desired use for POC tests than Australia, Belgium and the Netherlands. Our limited data suggest (but do not confirm) representativeness. Conclusions: Primary care clinicians in all five countries expressed a desire for POC tests to help them diagnose a range of acute and chronic conditions. Rates of current reported use and desired future use were generally high for a small selection of POC tests, but varied across countries. Future research is warranted to explore how specific POC tests might improve primary care. [ABSTRACT FROM AUTHOR]

An essay is presented on the crisis in evidence-based medicine especially in the wide variation used in the implementation of an evidence-based practice in Great Britain. Topics include distortion of evidence-based brand in which the quality mark is misrepresented and misappropriated, evidence-based medicine as a science of marginal gains and a shift from disease to risk, and overemphasis on algorithmic rules. Also discussed is a recommendation to return to real evidence-based medicine.

Letters are presented in response to several articles including "Forty years of sports performance research and little insight gained," by C. Heneghan and colleagues, and "How valid is the European Food Safety Authority's assessment of sports drinks," by C. Cohen and colleagues, in the July 2012 issue; responses to few of these letters are also presented.

Background: To assess the extent and nature of claims regarding improved sports performance made by advertisers for a broad range of sports-related products, and the quality of the evidence on which these claims are based. Methods: The authors analysed magazine adverts and associated websites of a broad range of sports products. The authors searched for references supporting the performance and/or recovery claims of these products. The authors critically appraised the methods in the retrieved references by assessing the level of evidence and the risk of bias. The authors also collected information on the included participants, adverse events, study limitations, the primary outcome of interest and whether the intervention had been retested. Results: The authors viewed 1035 web pages and identified 431 performance-enhancing claims for 104 different products. The authors found 146 references that underpinned these claims. More than half (52.8%) of the websites that made performance claims did not provide any references, and the authors were unable to perform critical appraisal for approximately half (72/146) of the identified references. None of the references referred to systematic reviews (level 1 evidence). Of the critically appraised studies, 84% were judged to be at high risk of bias. Randomisation was used in just over half of the studies (58.1%), allocation concealment was only clear in five (6.8%) studies; and blinding of the investigators, outcome assessors or participants was only clearly reported as used in 20 (27.0%) studies. Only three of the 74 (2.7%) studies were judged to be of high quality and at low risk of bias. Conclusions: The current evidence is not of sufficient quality to inform the public about the benefits and harms of sports products. There is a need to improve the quality and reporting of research, a move towards using systematic review evidence to inform decisions. [ABSTRACT FROM AUTHOR]

Introduction: Placebos have long provided a robust control for evaluating active pharmacological preparations, but frequently demonstrate a variable therapeutic effect when delivered in double-blinded placebo-controlled trials. Delivery of placebos as treatment alone has been considered unethical, as it has been thought that deception is essential for their effect. However, recent evidence suggests that clinical benefit can be derived from placebos delivered without deception (unblinded/open-label) manner. Here, we present a protocol for the first systematic review and meta-analysis of studies of the effects of non-deceptive placebos compared with no treatment. Methods and analysis This protocol will compare the effect of placebos delivered non-deceptively to no treatment. It will also assess the methods of delivery used for non-deceptive placebos. Studies will be sought through relevant database searches and will include those within disease settings and those among healthy controls. To be included, trials must include both non-deceptive (open-label) placebo and no treatment groups. All data extraction and analysis will be conducted by two independent reviewers. The analysis will evaluate any differences in outcome measures between the non-deceptive placebo and no treatment groups. Outcome measures will be the clinically-relevant outcomes detailed in the primary papers. The delivery methods, such as verbal instructions, which may provide positive expectations and outcomes, of non-deceptive placebos will also be assessed. Each study will be comprehensively assessed for bias. Subgroup analyses will identify any discrepancies among heterogeneous data. Ethics and dissemination This review does not require ethical approval. The completed review will be widely disseminated by publication and social media where appropriate. This protocol has been registered on PROSPERO (2015:CRD42015023347).

In August 2011, a group of medical doctors, ethicists, academic and medical physicists were asked to debate and reach consensus on the potential need for randomised control trials to test charged particle radiation therapy (CPRT) for treating tumours. The outcome of the meeting was a paper recently published in the Journal of Medical Ethics entitled "Position statement on ethics, equipoise and research on charged particle therapy" by Sheehan et al. However 6 of the 30 meeting participants withdrew from authorship of the 'position statement' because their views were not adequately represented. The 'position statement' did not state our reasons for withdrawing from the statement, which is a considerable omission. We had two principal objections: (1) the case for the benefits to patients and society of randomized trials to test CPRT was not adequately represented, and (2) the complexities and potential harms of CPRT were not clearly stated. In this response we explain and justify our objections. Patients, doctors and policymakers seeking to make independent judgments about whether equipoise exists for the relative benefits of CPRT should therefore read this document alongside the 'position' statement. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "It's time to put the placebo out of its misery," by R. Nunn, in the April 20, 2009 issue.

Unlike its friendly cousin the placebo effect, the nocebo effect (the effect of expecting a negative outcome) has been almost ignored. Epistemic and ethical confusions related to its existence have gone all but unnoticed. Contrary to what is often asserted, adverse events following from taking placebo interventions are not necessarily nocebo effects; they could have arisen due to natural history. Meanwhile, ethical informed consent (in clinical trials and clinical practice) has centred almost exclusively on the need to inform patients about intervention risks with patients to preserve their autonomy. Researchers have failed to consider the harm caused by the way in which the information is conveyed. In this paper, I argue that the magnitude of nocebo effects must be measured using control groups consisting of untreated patients. And, because the nocebo effect can produce harm, the principle of non-maleficence must be taken into account alongside autonomy when obtaining (ethical) informed consent and communicating intervention risks with patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)