CONSORT-Statement Guideline for Reporting Clinical Trial Ji-Qian Fang School of Public Health Sun Yat-Sen University Inadequate reporting damages RCT The whole of medicine depends on the transparent reporting of clinical trials Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Inadequate reporting and design are associated with biased estimates of treatment effects. History of CONSORT 1994, two groups of editors, statisticians and medical workers published their suggestions separately (JAMA) 1995, they co-worked out a CONSORT-statement (JAMA) 2001, The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials published in ANN Intern Med., JAMA and Lancet on behalf the The CONSORT Group Supported by many medical journals such as British Medical Journal, Annals of Internal Medicine CONSORT 2010 Statement Annals Internal Medicine, 24 March 2010 CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials Also published by BMJ, The Lancet, Obstetrics & Gynecology, PLoS Medicine, Open Medicine, Journal of Clinical Epidemiology, BMC Medicine, Trials. Although the 2001 CONSORT has improved the quality of some RCT reports, there still are many problems; and since 2001, the CONSORT group has further accumulated a number of new evidences and experience.
1. Check list of CONSORT Flow diagram Title Item 1a. Identification as a randomised trial in the title Method Item 3a. Eligibility criteria for participants Example Smoking reduction with oral nicotine inhalers: double blind, randomized clinical trial of efficacy and safety. Eligibility criteria :age, gender, clinical diagnosis, symptoms Exclusion criteria :for the safety of patients; and convenience of research ---- Let the readers know the precise population that the conclusion of the article holds for
Item 3a. Eligibility criteria for participants all women who were menstruating regularly and who were between 20 and 44 years of age, were candidates for inclusion in the study. They were not admitted to the study if any of the following criteria were present: (1) a history of ectopic pregnancy, (2) pregnancy within the past 42 days,. (9) residence outside the city of Nairobi, insufficient address for follow-up, or unwillingness to return for follow-up. Item 3b. The settings and locations where the data were collected ---- Settings and locations indicates the source of data Volunteers were recruited in London from four general practices and the ear, nose, and throat outpatient department of Northwick Park Hospital. The prescribers were familiar with homoeopathic principles but were not experienced in homoeopathic immunotherapy. Item 5. Specific objectives and hypotheses Objectives:the problems intend to answer Hypotheses:the conclusions to be tested We tested the hypothesis that a policy of active management of nulliparous labour would: 1. reduce the rate of caesarean section, 2. reduce the rate of prolonged labour; 3. not influence maternal satisfaction with the birth experience. Item 6a. Clearly defined primary and secondary outcome measures primary outcome measure should be determined in advance, and the sample size is estimated based on it. The primary endpoint with respect to efficacy in psoriasis was the proportion of patients achieving a 75% improvement in psoriasis activity from baseline to 12 weeks as measured by the PASI [psoriasis area and severity index]. Additional analyses were done on the percentage change in PASI scores and improvement in target psoriasis lesions.
Item 6b. When applicable, any methods used to enhance the quality of measurements The clinical end point committee... evaluated all clinical events in a blinded fashion and end points were determined by unanimous decision. Blood pressure (diastolic phase 5) while the patient was sitting and had rested for at least five minutes was measured by a trained nurse with a Copal UA-251 or a Takeda UA-751 electronic auscultatory blood pressure reading machine Item 7a. How sample size was determined The 4 elements for sample size estimation: 1) Minimal difference between the 2 groups 2) Variance within each group 3) Allowed probability of type I error 4) Allowed probability of type II error β (power 1- β) We believed that...theincidenceofsymptomatic deep venous thrombosis or pulmonary embolism or death would be 4% in the placebo group and 1.5% in the ardeparin sodium group. Based on 0.9 power to detect a significant difference (P < 0.05, twosided), 976 patients were required for each study group. Item 8a. Method used to generate the random allocation sequence Women had an equal probability of assignment to the groups. The randomization code was developed using a computer random number generator Independent pharmacists dispensed either active or placebo inhalers according to a computer generated randomization list Item 8a. Method used to generate the random allocation sequence Why randomization is so important? (1) Avoid bias; (2) Prepare for blinding; (3) Necessary for statistical analysis Report the details on randomization Not simply random allocation, randomization Simple randomization? Restricted randomization?
Item 8b. Details of any restriction of randomization Block randomization How to generate blocks? Size of block?fixed or not? using a computer random number generator to select random permuted blocks. The block lengths were 4, 8, and 10 varied randomly... Stratified randomization How to stratify? Male, female; Young, old; Hospital 1,2,3, Item 9. Method used to implement the random allocation sequence and whether the sequence was concealed Successful randomization: (1) Generating an unpredictable series; (2) Allocation concealment Fail concealment leads to fail in randomization Concealment be implemented by a third party Ex. Central randomization system; The drug should be dispended by the pharmacy Item 9. Method used to implement the random allocation sequence and whether the sequence was concealed Women were assigned on an individual basis to both vitamins C and E or to both placebo treatments A computer generated randomization list was drawn up by the statistician and given to the pharmacy departments. The researchers responsible for seeing the pregnant women allocated the next available number on entry into the trial. Each woman collected her tablets direct from the pharmacy department. Item 11a. Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment Exemple: the details of the series were unknown to any of the investigators or to the coordinator and were contained in a set of sealed envelopes, each bearing on the outside only the name of the hospital and a number. All study personnel and participants were blinded to treatment assignment for the duration of the study. Only the study statisticians and the data monitoring committee saw unblinded data, but none had any contact with study participants.
Item 11b. If done, how the success of blinding was evaluated Exemple: To evaluate patient blinding, the questionnaire asked patients to indicate which treatment they believed they had received (acupuncture, placebo, or don t know) at 3 points in time... If patients answered either acupuncture or placebo, they were asked to indicate what led to that belief Item 12a. Statistical methods used to compare groups for primary outcome(s) Protocol Indicate all the statistical methods to be used for the primary outcome Report Whether the methods used were planed in the Protocol? Post hoc methods Mostly lead to bias! Do not recommended Item 12a. Statistical methods used to compare groups for primary outcome(s) Exemple: All data analysis was carried out according to a preestablished analysis plan. Proportions were compared by using 2 tests with continuity correction or Fisher s exact test when appropriate. Multivariate analyses were conducted with logistic regression. The durations of episodes and signs of disease were compared by using proportional hazards regression. Mean serum retinol concentrations were compared by t test and analysis of covariance... Two sided significance tests were used throughout. Item 12b. Methods for additional analyses, such as subgroup analyses and adjusted analyses Post hoc subgroup comparisons is subject to the analysis reminded by the data, usually not trustable! Adjustment analysis also should be planned in advance (1) Adjust for stratified variable (item 8b) (2) Adjust for incomparable in baseline (item 16) The results of Post hoc analyses should not be report in the part of results ; if necessary, could be a sort of exploratory ones.
Results Item 13a. Flow of participants ( strongly recommended) Item 13b. Describe protocol deviations from study as planned, together with reasons. Any deviation from the planned protocol should be reported: Intervention? Tests? Data collection? Statistical methods? Try to explain the nature of the deviations: The balance due to randomization had been damaged or not? If some deviation happened after randomization, the reason should explained clearly in the text or the flow chart Item 13b. Describe protocol deviations from study as planned, together with reasons Exemple: There was only one protocol deviation, in a woman in the study group. She had an abnormal pelvic measurement and was scheduled for elective caesarean section. However, the attending obstetrician judged a trial of labour acceptable; caesarean section was done when there was no progress in the first stage of labour. Item 16. Number of participants (denominator) in each group included in each analysis and whether the analysis was by intention-to-treat Intention-to-treat is important principle in clinical trial, which means: All data of the participants assigned by randomization should be put in analysis; All data of the participants should devote to the group initially assigned by randomization It is a necessary conservative measure for the study of efficacy, but not appropriate to study on safety
Item 16. Number of participants (denominator) in each group included in each analysis and whether the analysis was by intention-to-treat. Exemple: The primary analysis was intention-to-treat and involved all patients who were randomly assigned... One patient in the alendronate group was lost to follow up; thus data from 31 patients were available for the intention-to-treat analysis. Fivepatientswereconsideredprotocolviolators... consequently 26 patients remained for the perprotocol analyses (152). Discussion Item 20. Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses. There must be problems with potential bias and imprecision in any researches. If the authors do not recognize the limitation of their own work, it must not be a research,perhaps something else. Item 22. Interpretation consistent with results, balancing benefits and harms, and considering orther relevant evidence The CONSORT Group expressed concerns: Conclusions in papers frequently misrepresented the actual analytical results And the harms were ignored or marginalized. Others Item 23. Registration number and name of trial registry Empirical evidence supports the need for trial registration Recent requirements by the journal editors have fostered compliance -- September of 2004, the International Committee of Medical Journal Editors(ICMJE)changed their policy to that the article might be considered to publish when only when the registration had been completed before the first case was enrolled.
世界卫生组织 : International Clinical Trials Registry Platform (ICTRP) 美国国立卫生院 : A service of the U.S. National Institutes of Health Item 24. Where the full trial protocol can be accessed, if any Empirical evidence suggests that authors often ignore, in the conduct and reporting of their trial, what they stated in the protocol. Hence, avalibility of the protocol can instigate adherence to the protocol before publication and facilitate assessment of adherence after publication. Item 25. Sources of funding and other support (such as supply of drugs), role of funders Empirical evidence points toward funding source sometimes being associated with estimated treatment effect.
Summary (1) In terms of evidence medicine, RCT provides relatively strong evidence for efficacy study If RCT does not perform properly, the bias might mislead the readers Bias could be deducted by closely focusing on the design of clinical trial Randomization and blinding are effective measures dealing with bias Summary (2) The keys in evaluation of a clinical trial Concealment in randomization (Mother et al.,1998); Blinding to patients and physicians (Schulz et al.,1995); intention to treat (ITT) analysis Summary Web site of CONSORT (3) The CONSORT statement is useful: Promote the quality of reporting clinical trials; Help the Journal editors to evaluate the medical articles; Help the researchers design their medical study. http://www.consort-statement.org (Leah Lepage; e-mail, llepage@uottawa.ca).
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