• Humans
• Neoplasms/drug therapy
• Drug Approval
• United States
• Clinical Trials, Phase II as Topic/statistics & numerical data
• United States Food and Drug Administration
• Antineoplastic Agents/therapeutic use
• Medical Oncology

• PJT-175217 CIHR
• CIHR
• PJT-175217 CIHR
• Navigating the Valley of Death
• Canadian Institutes of Health Research

• Autonomy cultural differences
• Informed consent
• Randomised controlled trials
• Shared decision making
• Young people

• Humans
• Informed Consent/ethics
• Pakistan
• Qualitative Research
• Female
• Personal Autonomy
• Male
• Decision Making
• Adult
• Randomized Controlled Trials as Topic/ethics
• Middle Aged
• Attitude of Health Personnel
• Coercion
• Family
• Mental Competency
• Patient Selection/ethics

• MR/R022461/1 Medical Research Council
• MR/R022461/1 Medical Research Council
• MR/R022461/1 Medical Research Council
• MR/R022461/1 Medical Research Council
• MR/R022461/1 Medical Research Council
• MR/R022461/1 Medical Research Council

• AO spine thoracolumbar injury classification system
• equipoise
• reliability
• thoracolumbar fractures

• AO Spine Knowledge Forum Trauma
• AO Network Clinical Research

• Bayesian inference
• clinical trial design
• evidence regression
• strength of evidence

• Humans
• Bayes Theorem
• Clinical Trials as Topic
• Probability
• Research Design
• Sample Size

• AstraZeneca PLC Research and Development

• Culture
• Equipoise
• Evidence-base
• Randomised clinical trials
• Self-harm
• Suicide

• Adolescent
• Humans
• Pakistan
• Patient Selection
• Uncertainty
• Treatment Outcome
• Self-Injurious Behavior/diagnosis
• Self-Injurious Behavior/therapy
• Randomized Controlled Trials as Topic

• MR/P028144/1 Medical Research Council

• 10 years
• Consensus
• Early onset scoliosis
• Treatment options
• Uncertainty

• Child
• Humans
• Scoliosis/surgery
• Scoliosis/epidemiology
• Uncertainty
• Consensus
• Spine
• Surveys and Questionnaires

• car seat test
• intermittent hypoxemia
• cardiorespiratory instability
• premature infant

• Child Restraint Systems
• Humans
• Infant Equipment
• Infant, Newborn
• Infant, Premature
• Mass Screening
• Surveys and Questionnaires

• K23 HL136843 NHLBI NIH HHS
• U10 HD068244 NICHD NIH HHS
• UG1 HD068244 NICHD NIH HHS

• critical care
• negative predictive value
• positive predictive value
• power
• randomized controlled trial

Misinterpretations of the p-value in null-hypothesis statistical testing are common. We aimed to determine the implications of observed p-values in critical care randomized controlled trials (RCTs).

We included three cohorts of published RCTs: Adult-RCTs reporting a mortality outcome, Pediatric-RCTs reporting a mortality outcome, and recent Consecutive-RCTs reporting p-value ≤.10 in six higher-impact journals. We recorded descriptive information from RCTs. Reverse Bayesian implications of obtained p-values were calculated, reported as percentages with inter-quartile ranges.

Obtained p-value was ≤.005 in 11/216 (5.1%) Adult-RCTs, 2/120 (1.7%) Pediatric-RCTs, and 37/90 (41.1%) Consecutive-RCTs. An obtained p-value .05–.0051 had high False Positive Rates; in Adult-RCTs, minimum (assuming prior probability of the alternative hypothesis was 50%) and realistic (assuming prior probability of the alternative hypothesis was 10%) False Positive Rates were 16.7% [11.2, 21.8] and 64.3% [53.2, 71.4]. An obtained p-value ≤.005 had lower False Positive Rates; in Adult-RCTs the realistic False Positive Rate was 7.7% [7.7, 16.0]. The realistic probability of the alternative hypothesis for obtained p-value .05–.0051 (ie, Positive Predictive Value) was 28.0% [24.1, 34.8], 30.6% [27.7, 48.5], 29.3% [24.3, 41.0], and 32.7% [24.1, 43.5] for Adult-RCTs, Pediatric-RCTs, Consecutive-RCTs primary and secondary outcome, respectively. The maximum Positive Predictive Value for p-value category .05–.0051 was median 77.8%, 79.8%, 78.8%, and 81.4% respectively. To have maximum or realistic Positive Predictive Value >90% or >80%, RCTs needed to have obtained p-value ≤.005. The credibility of p-value .05–.0051 findings were easy to challenge, and the credibility to rule-out an effect with p-value >.05 to .10 was low. The probability that a replication study would obtain p-value ≤.05 did not approach 90% unless the obtained p-value was ≤.005.

Unless the obtained p-value was ≤.005, the False Positive Rate was high, and the Positive Predictive Value and probability of replication of “statistically significant” findings were low.

• Bayesian
• critical care
• false positive rate
• p-value
• positive predictive value
• randomized controlled trial

• Ethics
• Pediatric surgery
• Randomized control trial (RCT)

• Breast Neoplasms/economics
• Breast Neoplasms/mortality
• Breast Neoplasms/therapy
• Clinical Trials, Phase II as Topic/economics
• Clinical Trials, Phase II as Topic/methods
• Clinical Trials, Phase III as Topic/economics
• Clinical Trials, Phase III as Topic/methods
• Cost-Benefit Analysis
• Female
• Humans
• Models, Economic
• Pancreatic Neoplasms/economics
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/therapy
• Quality-Adjusted Life Years
• Research Design/standards
• Technology Assessment, Biomedical/economics
• Uncertainty

• UG1 CA189974 NCI NIH HHS
• ME-1303-5889 Patient-Centered Outcomes Research Institute

• Clinical practice guidelines
• Consensus
• Hemorrhoids
• Survey

• P30 AG024928 NIA NIH HHS

• clinical equipoise
• questionnaire
• surgery
• survey

• Attitude of Health Personnel
• Australasia/epidemiology
• Colorectal Surgery/statistics & numerical data
• Evaluation Studies as Topic
• Female
• General Surgery/education
• General Surgery/statistics & numerical data
• Guideline Adherence/statistics & numerical data
• Health Care Surveys/standards
• Health Care Surveys/statistics & numerical data
• Humans
• Male
• Observational Studies as Topic
• Practice Patterns, Physicians'
• Randomized Controlled Trials as Topic

• Anal fissure
• clinical practice
• guidelines
• survey

• Adult
• Australia
• Botulinum Toxins, Type A/therapeutic use
• Female
• Fissure in Ano/surgery
• Guideline Adherence
• Humans
• Male
• Middle Aged
• New Zealand
• Practice Patterns, Physicians'/statistics & numerical data
• Surgical Flaps

• Autonomy
• Clinical trials
• NGOs
• Public Health Ethics
• Research Ethics

• Africa, Western
• Compassionate Use Trials
• Disasters
• Disease Outbreaks
• Ethical Analysis
• Ethics, Research
• Hemorrhagic Fever, Ebola/epidemiology
• Hemorrhagic Fever, Ebola/therapy
• Humans
• Public Health
• Research Design
• Therapeutic Human Experimentation/ethics
• Therapies, Investigational
• Adaptive Clinical Trials as Topic

• Clinical practice guidelines
• Consensus
• Diverticulitis

• Anterior resection
• Bias
• Decision-making
• Heuristics
• Stoma
• Surgical stomas

• Adult
• Bias
• Demography
• Female
• Heuristics
• Humans
• Male
• Middle Aged
• Rectum/surgery
• Regression Analysis
• Risk Factors
• Surgeons
• Surgical Stomas
• Surveys and Questionnaires

• Equipoise
• Multicentre
• Patient preferences
• Qualitative
• Recruitment
• Surgical trial
• Trial design
• Trials

• Humans
• Interviews as Topic
• Male
• Patient Preference
• Patient Selection
• Qualitative Research
• Recurrence
• Research Subjects/psychology
• Sample Size
• Severity of Illness Index
• Therapeutic Equipoise
• United Kingdom
• Urethral Stricture/diagnosis
• Urethral Stricture/physiopathology
• Urethral Stricture/psychology
• Urethral Stricture/surgery
• Urologic Surgical Procedures, Male/adverse effects
• Urologic Surgical Procedures, Male/methods

• 10/57/23 Department of Health
• Health Technology Assessment Programme

• Clinical Trials as Topic/ethics
• Clinical Trials as Topic/methods
• Humans
• Patient Selection
• Selection Bias

• Angioplasty, Balloon, Coronary
• Attitude of Health Personnel
• Clinical Trials Data Monitoring Committees/ethics
• Costs and Cost Analysis
• Eptifibatide
• Ethics, Research
• Humans
• Multicenter Studies as Topic
• Patient Selection
• Peptides/therapeutic use
• Physicians
• Placebos
• Platelet Aggregation Inhibitors/therapeutic use
• Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors
• Randomized Controlled Trials as Topic/ethics
• Research Design
• Social Responsibility
• Stents
• United States
• United States Food and Drug Administration

• Aged
• Aged, 80 and over
• Decompression, Surgical/methods
• Female
• Follow-Up Studies
• Humans
• Laminectomy/instrumentation
• Laminectomy/methods
• Lumbar Vertebrae
• Male
• Middle Aged
• Patient Selection
• Practice Guidelines as Topic
• Prospective Studies
• Spinal Stenosis/diagnostic imaging
• Spinal Stenosis/surgery
• Spondylolisthesis/diagnostic imaging
• Spondylolisthesis/surgery
• Treatment Outcome
• United States

• detailed methodology
• qualitative methods
• resource allocation
• value of information

• Radiotherapy
• cancer
• clinical trials
• meta-analysis
• radiation physics
• radiobiology

Three arguments are usually invoked in favour of stepped wedge cluster randomised controlled trials: the logistic convenience of implementing an intervention in phases, the ethical benefit of providing the intervention to all clusters, and the potential to enhance the social acceptability of cluster randomised controlled trials. Are these alleged benefits real? We explored the logistic, ethical, and political dimensions of stepped wedge trials using case studies of six recent evaluations.

We identified completed or ongoing stepped wedge evaluations using two systematic reviews. We then purposively selected six with a focus on public health in high, middle, and low-income settings. We interviewed their authors about the logistic, ethical, and social issues faced by their teams. Two authors reviewed interview transcripts, identified emerging issues through qualitative thematic analysis, reflected upon them in the context of the literature, and invited all participants to co-author the manuscript.

Our analysis raises three main points. First, the phased implementation of interventions can alleviate problems linked to simultaneous roll-out, but also brings new challenges. Issues to consider include the feasibility of organising intervention activities according to a randomised sequence, estimating time lags in implementation and effects, and accommodating policy changes during the trial period. Second, stepped wedge trials, like parallel cluster trials, require equipoise: without it, randomising participants to a control condition, even for a short time, remains problematic. In stepped wedge trials, equipoise is likely to lie in the degree of effect, effectiveness in a specific operational milieu, and the balance of benefit and harm, including the social value of better evaluation. Third, the strongest arguments for a stepped wedge design are logistic and political rather than ethical. The design is advantageous when simultaneous roll-out is impractical and when it increases the acceptability of using counterfactuals.

The logistic convenience of phased implementation is context-dependent, and may be vitiated by the additional requirements of phasing. The potential for stepped wedge trials to enhance the social acceptability of cluster randomised trials is real, but their ethical legitimacy still rests on demonstrating equipoise and its configuration for each research question and setting.

• Adult
• Attitude of Health Personnel
• Australia
• Colectomy/methods
• Colectomy/statistics & numerical data
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Colorectal Neoplasms/therapy
• Confidence Intervals
• Decision Making
• Female
• Follow-Up Studies
• Humans
• Intestinal Obstruction/pathology
• Intestinal Obstruction/surgery
• Intestinal Obstruction/therapy
• Male
• Middle Aged
• Minimally Invasive Surgical Procedures/methods
• Minimally Invasive Surgical Procedures/statistics & numerical data
• New Zealand
• Patient Selection
• Practice Patterns, Physicians'
• Societies, Medical
• Stents/statistics & numerical data
• Surveys and Questionnaires
• Treatment Outcome

• Anévrisme cérébral
• Clip or coil
• Clip ou coil
• Clipping
• Coiling
• Endovascular treatment
• Intracranial aneurysms
• Surgical treatment
• Traitement chirurgical
• Traitement endovasculaire

• Adult
• Aged
• Female
• Humans
• Intracranial Aneurysm/surgery
• Male
• Middle Aged
• Neurosurgical Procedures
• Practice Patterns, Physicians'
• Surveys and Questionnaires
• Vascular Surgical Procedures

• Biomedical Research
• Humans
• Randomized Controlled Trials as Topic/ethics
• Uncertainty

The conduct of a randomized controlled trial (RCT) is deemed ethical only if we are in state of “equipoise” as to which treatment would be most beneficial for the patients. Individual equipoise applies to an individual clinician or a member of ethical, institutional review board (IRB), whilst collective equipoise refers to the profession as a whole. It is argued that physicians are not bound by the equipoise but their actions are directed by the confines of the expert opinion. Experts can agree or disagree in various proportions on the merit of a given treatment. Hence, the collective equipoise will be often incomplete. In turn, the opinions of content expert in the field of the proposed trial influence the IRB members’ decision regarding trial approval.

We conducted a survey of IRB members at University of South Florida and the IRB members attending the bioethics conference organized in Clearwater, Florida, USA. The survey was made available as hard copy (paper based) and included six hypothetical scenarios outlining clinical trials targeted at measuring the collective equipoise. We defined the collective equipoise as the situation when survey participants were equally split (50:50) in their decision regarding whether a proposed clinical trial would be ethical to conduct. The opinion of 100 experts in the field expressed as proportion of experts favoring treatment A vs. B in each of the five scenarios was made available to the participants.

The response rate of our survey was 33% (71/218). Fifty percent of the IRB members would approve an RCT addressing the efficacy of two drugs for the management of headache even if 80% of experts favor one treatment over another (median: 80%; third quartile: 80%). Similarly, half of participating IRB members would approve the study when the median distribution of equipoise among experts was 70% (70 in favor of treatment A vs. 30 in favor of treatment B) for treatment of leukemia, 60% for treatment of geriatric patients and 70% for treatment of newborns. Half of IRB members would approve the study when the median distribution of equipoise among experts was 70% for treatment for leukemia in dogs and 85% for leukemia in rats (and 25% of IRB members would approve such a study even if 100% of experts favors one treatment over another). None of the demographic features of respondents affected collective equipoise.

This is the first study assessing collective equipoise among ethical committee/IRB members. Our study findings show that IRB members perceived that conduct of a trial enrolling humans is unethical when the equipoise level is beyond 80% (80:20 distribution of uncertainty). IRB members require a higher level of equipoise when it comes to testing a new drug in humans than in animals. A relatively high level of equipoise is needed for IRB members to be comfortable to approve trials involving life-threatening situations, children and elderly patients.

• Ethical committees.
• ethics
• randomized controlled trial

• Clinical Trials
• Dental
• Ethics
• Iran
• Journal

Evidence regarding whether or not antibiotic prophylaxis is beneficial in preventing post-operative surgical site infection in adult inguinal hernia repair is conflicting. A recent Cochrane review based on 17 randomised trials did not reach a conclusion on this subject. This study aimed to describe the current practice and determine whether clinical equipoise is prevalent.

Surgeons in training were recruited to administer the Survey of Hernia Antibiotic Prophylaxis usE survey to consultant-level general surgeons in London and the south-east of England on their practices and beliefs regarding antibiotic prophylaxis in adult elective inguinal hernia repair. Local prophylaxis guidelines for the participating hospital sites were also determined.

The study was conducted at 34 different sites and received completed surveys from 229 out of a possible 245 surgeons, a 93 % response rate. Overall, a large majority of hospital guidelines (22/28) and surgeons’ personal beliefs (192/229, 84 %) supported the use of single-dose pre-operative intravenous antibiotic prophylaxis in inguinal hernia repair, although there was considerable variation in the regimens in use. The most widely used regimen was intravenous co-amoxiclav (1.2 g). Less than half of surgeons were adherent to their own hospital antibiotic guidelines for this procedure, although many incorrectly believed that they were following these.

In the south-east of England, there is a strong majority of surgical opinion in favour of the use of antibiotic prophylaxis in this procedure. It is therefore likely to be extremely difficult to conduct further randomised studies in the UK to support or refute the effectiveness of prophylaxis in this commonly performed procedure.

• Academies and Institutes
• Clinical Trials, Phase III as Topic
• Humans
• Industry
• Neoplasms/therapy
• Odds Ratio
• Randomized Controlled Trials as Topic
• Treatment Outcome

• R01 CA140408 NCI NIH HHS
• 1R01CA140408-01/02 NCI NIH HHS

The number of surgical procedures performed each year to treat femoroacetabular impingement (FAI) continues to rise. Although there is evidence that surgery can improve symptoms in the short-term, there is no evidence that it slows the development of osteoarthritis (OA). We performed a feasibility study to determine whether patient and surgeon opinion was permissive for a Randomised Controlled Trial (RCT) comparing operative with non-operative treatment for FAI.

Surgeon opinion was obtained using validated questionnaires at a Specialist Hip Meeting (n = 61, 30 of whom stated that they routinely performed FAI surgery) and patient opinion was obtained from clinical patients with a new diagnosis of FAI (n = 31).

Clinical equipoise was demonstrated when surgeons were given clinical scenarios and asked whether they would manage a patient operatively or non-operatively. A total of 23 surgeons (77%) who routinely perform FAI surgery were willing to recruit patients into a RCT, and 28 patients (90%) were willing to participate. 75% of responding surgeons believed it was appropriate to randomise patients to non-operative treatment for ≥ 12 months. Conversely, only eight patients (26%) felt this was acceptable, although 29 (94%) were willing to continue non-operative treatment for six months. More patients were concerned about their risk of developing OA than their current symptoms, although most patients felt that the two were of equal importance.

We conclude that a RCT comparing operative and non-operative management of FAI is feasible and should be considered a research priority. An important finding for orthopaedic surgical trials is that patients without life-threatening pathology appear willing to trial a treatment for six months without improvement in their symptoms.

• Equipoise
• Feasibility
• Femoroacetabular impingement
• Hip
• Randomised controlled trial
• Trial design

• Bias
• Clinical Equipoise
• Manual Therapy
• Personal Equipoise

• Clinical Trials as Topic/ethics
• Clinical Trials as Topic/psychology
• Emotions
• Ethical Theory
• Female
• Game Theory
• Guilt
• Humans
• Male
• Monte Carlo Method
• Moral Obligations
• Patient Participation
• Rationalization
• Researcher-Subject Relations/ethics
• Researcher-Subject Relations/psychology
• Risk Assessment/methods
• Sensitivity and Specificity
• Social Values
• Surveys and Questionnaires
• Trust

• Bias
• Clinical Equipoise
• Manual Therapy
• Personal Equipoise

Randomised controlled trials are being increasingly used to evaluate new surgical interventions. There are a number of problematic methodological issues specific to surgical trials, the most important being identifying whether patients are eligible for recruitment into the trial. This is in part due to the diversity in practice patterns across institutions and the enormous range of available interventions that often leads to a low level of agreement between clinicians about both the value and the appropriate choice of intervention. We argue that a clinician should offer patients the option of recruitment into a trial, even if the clinician is not individually in a position of equipoise, if there is collective (clinical) equipoise amongst the wider clinical community about the effectiveness of a proposed intervention (the clinical equipoise principle). We show how this process can work using data collected from an ongoing trial of a surgical intervention.

We describe a statistical framework for the assessment of uncertainty prior to patient recruitment to a clinical trial using a panel of expert clinical assessors and techniques for eliciting, pooling and modelling of expert opinions. The methodology is illustrated using example data from the UK Heel Fracture Trial. The statistical modelling provided results that were clear and simple to present to clinicians and showed how decisions regarding recruitment were influenced by both the collective opinion of the expert panel and the type of decision rule selected.

The statistical framework presented has potential to identify eligible patients and assist in the simplification of eligibility criteria which might encourage greater participation in clinical trials evaluating surgical interventions.

• Biomedical Technology/economics
• Evidence-Based Medicine/classification
• Evidence-Based Medicine/economics
• Humans
• National Cancer Institute (U.S.)
• Randomized Controlled Trials as Topic/classification
• Randomized Controlled Trials as Topic/economics
• Research Design
• Research Support as Topic
• Risk Assessment
• Terminology as Topic
• Therapeutic Equipoise
• Treatment Outcome
• United Kingdom
• United States

• Controlled
• Design
• Plastic
• Randomized
• Surgery
• Trials