scholarly journals Multiple secondary outcome analyses: precise interpretation is important

Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Richard A. Parker ◽  
Christopher J. Weir

AbstractAnalysis of multiple secondary outcomes in a clinical trial leads to an increased probability of at least one false significant result among all secondary outcomes studied. In this paper, we question the notion that that if no multiplicity adjustment has been applied to multiple secondary outcome analyses in a clinical trial, then they must necessarily be regarded as exploratory. Instead, we argue that if individual secondary outcome results are interpreted carefully and precisely, there is no need to downgrade our interpretation to exploratory. This is because the probability of a false significant result for each comparison, the per-comparison wise error rate, does not increase with multiple testing. Strong effects on secondary outcomes should always be taken seriously and must not be dismissed purely on the basis of multiplicity concerns.

Author(s):  
Ana Sanader Vucemilovic ◽  
Livia Puljak

Aim: Psoriasis includes unpleasant symptoms such as pain. This study aimed to investigate whether clinical trials have domains related to pain in their study designs. Materials and methods: We analyzed all clinical trials about interventions for psoriasis treatment registered on ClinicalTrials.gov and the frequency of pain-related outcomes. Results: Our analysis included 1033 registered clinical trials. They had 1329 primary outcomes and 5457 secondary outcomes. The pain was used in six (0.6%) protocols as a primary outcome and 68 (6.5%) protocols as a secondary outcome. Conclusion: Pain as an outcome was used in few registered clinical trial protocols for the treatment of psoriatic conditions. Future studies should investigate why the trialists do not include pain among primary or secondary outcomes.


2015 ◽  
pp. 214-228 ◽  

Objective: To describe the design and methodology of the Convergence Insufficiency Treatment Trial: Attention and Reading Trial (CITT-ART), the first randomized clinical trial evaluating the effect of vision therapy on reading and attention in school-age children with symptomatic convergence insufficiency (CI). Methods: CITT-ART is a multicenter, placebo-controlled, randomized clinical trial of 324 children ages 9 to 14 years in grades 3 to 8 with symptomatic CI. Participants are randomized to 16 weeks of office-based vergence/accommodative therapy (OBVAT) or placebo therapy (OBPT), both supplemented with home therapy. The primary outcome measure is the change in the Wechsler Individual Achievement Test-Version 3 (WIAT-III) reading comprehension subtest score. Secondary outcome measures are changes in attention as measured by the Strengths and Weaknesses of Attention (SWAN) as reported by parents and teachers, tests of binocular visual function, and other measures of reading and attention. The long-term effects of treatment are assessed 1 year after treatment completion. All analyses will test the null hypothesis of no difference in outcomes between the two treatment groups. The study is entering its second year of recruitment. The final results will contribute to a better understanding of the relationship between the treatment of symptomatic CI and its effect on reading and attention. Conclusion: The study will provide an evidence base to help parents, eye professionals, educators, and other health care providers make informed decisions as they care for children with CI and reading and attention problems. Results may also generate additional hypothesis and guide the development of other scientific investigations of the relationships between visual disorders and other developmental disorders in children.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhuoran Kuang ◽  
◽  
Xiaoyan Li ◽  
Jianxiong Cai ◽  
Yaolong Chen ◽  
...  

Abstract Objective To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. Method We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. Results A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). Conclusion Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 524.1-525
Author(s):  
I. Aachari ◽  
K. Samia ◽  
T. Latifa ◽  
T. Fatima Zahrae ◽  
S. Afilal ◽  
...  

Background:The technique of Kinesio-Taping is a method of adhesive bandage exerting traction on the skin which would favorably influence the muscular and articular systems by reducing the pressure exerted on the subcutaneous mechanoreceptors thus reducing pain and muscle tension.Objectives:The aim of this study is to assess the effectiveness of Kinesio-Taping in the short and medium term on pain and function in patients with chronic nonspecific low back pain compared to a placebo.Methods:We conducted a double-blind, two-arm randomized clinical trial. The study should include a total of 70 patients randomized into 2 groups: Kinesio-Taping (n = 35) and control group (n = 35). To this date we have included 46 patients.All patients receives four I-shaped adhesive strips arranged in a star-like shape and applied to the most painful region of the lower back with a tension between 25% to 30% in the taping group. The placebo group received a taping procedure with no tension.Taping is applied three times (at baseline, fourth and eighth day). Patients are assessed at baseline, on day 14 and at 4 weeks by the Arabic version of the Oswestry Physical and Functional Disability Index (ODI) which is the primary outcome. The secondary outcomes are the assessment of pain and functional disability according to the visual analog scale (VAS) evaluated on a scale of 0 to 10, as well as Rolland-Morris score.Results:Both groups were comparable at baseline concerning the demographical and clinical characteristics (P > 0.05) (table 1). The result of repeated measures ANOVA showed a significant change in ODI score and in VAS for pain and functional disability as well as Rolland-Morris score in both groups. Using the ANCOVA, controlling for pre-test scores, a significant difference was found between the two groups (table 2).Table 1. Clinical characteristics of study population.Conclusion:Our clinical trial offers preliminary evidence on the superiority of Kinesio-Taping in the treatment chronic back pain compared to placebo concerning the reduction of pain and disability. Thus, it can be used as a complementary method in chronic non-specific low back pain.Table 2. Primary and secondary outcomes in the Kinesio-Taping and placebo group.Disclosure of Interests:None declared


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e041458
Author(s):  
Vicki Anderson ◽  
Vanessa C Rausa ◽  
Nicholas Anderson ◽  
Georgia Parkin ◽  
Cathriona Clarke ◽  
...  

IntroductionWhile most children recover from a concussion shortly after injury, approximately 30% experience persistent postconcussive symptoms (pPCS) beyond 1-month postinjury. Existing research into the treatment of pPCS have evaluated unimodal approaches, despite evidence suggesting that pPCS likely represent an interaction across various symptom clusters. The primary aim of this study is to evaluate the effectiveness of a multimodal, symptom-tailored intervention to accelerate symptom recovery and increase the proportion of children with resolved symptoms at 3 months postconcussion.Methods and analysisIn this open-label, assessor-blinded, randomised clinical trial, children with concussion aged 8–18 years will be recruited from The Royal Children’s Hospital (The RCH) emergency department, or referred by a clinician, within 17 days of initial injury. Based on parent ratings of their child’s PCS at ~10 days postinjury, symptomatic children (≥2 symptoms at least 1-point above those endorsed preinjury) will undergo a baseline assessment at 3 weeks postinjury and randomised into either Concussion Essentials (CE, n=108), a multimodal, interdisciplinary delivered, symptom-tailored treatment involving physiotherapy, psychology and education, or usual care (UC, n=108) study arms. CE participants will receive 1 hour of intervention each week, for up to 8 weeks or until pPCS resolve. A postprogramme assessment will be conducted at 3 months postinjury for all participants. Effectiveness of the CE intervention will be determined by the proportion of participants for whom pPCS have resolved at the postprogramme assessment (primary outcome) relative to the UC group. Secondary outcome analyses will examine whether children receiving CE are more likely to demonstrate resolution of pPCS, earlier return to normal activity, higher quality of life and a lower rate of utilisation of health services, compared with the UC group.Ethics and disseminationEthics were approved by The RCH Human Research Ethics Committee (HREC: 37100). Parent, and for mature minors, participant consent, will be obtained prior to commencement of the trial. Study results will be disseminated at international conferences and international peer-reviewed journals.Trial registration numberACTRN12617000418370; pre-results.


2021 ◽  
pp. 030802262110002
Author(s):  
Joanne Inman ◽  
Katrina Bannigan ◽  
Jacqueline Akhurst

Introduction The dearth of clinical trials of individualised occupational therapy with people with a diagnosis of psychosis limits the evidence base globally for occupational therapy practice. This study evaluated the feasibility of conducting a pragmatic clinical trial. Method Mixed methods design using a pragmatic perspective; two-centre, one-group pretest-posttest study, at six months. POINTER Occupational Intervention Specification captured routine individualised occupational therapy. Process evaluation included recruitment, retention, intervention delivery, fidelity, adherence and outcome measurement. The primary outcome was participation in activities of everyday life, measured by Time Use Survey, Participation Scale and Utrecht Scale for Evaluation of Rehabilitation-Participation. The Canadian Occupational Performance Measure measured self-reported experience of and satisfaction with occupational performance. The Short Form-36v2 Health Survey measured health-related quality of life, a secondary outcome. Participants’ experiences were explored using a questionnaire. Intervention providers’ perspectives were investigated via the POINTER occupational intervention log and focus groups. Results Recruitment was (20/36) and drop-out 20% (4/20). Fidelity was 77%, and adherence was good; POINTER had validity and utility. Outcome measurement was acceptable to participants, indicating increased participation in activities of everyday life. Conclusion A larger clinical trial is merited; recruitment processes need further exploration, and outcome measurement needs refining.


Author(s):  
Damian Clarke ◽  
Joseph P. Romano ◽  
Michael Wolf

When considering multiple-hypothesis tests simultaneously, standard statistical techniques will lead to overrejection of null hypotheses unless the multiplicity of the testing framework is explicitly considered. In this article, we discuss the Romano–Wolf multiple-hypothesis correction and document its implementation in Stata. The Romano–Wolf correction (asymptotically) controls the familywise error rate, that is, the probability of rejecting at least one true null hypothesis among a family of hypotheses under test. This correction is considerably more powerful than earlier multiple-testing procedures, such as the Bonferroni and Holm corrections, given that it takes into account the dependence structure of the test statistics by resampling from the original data. We describe a command, rwolf, that implements this correction and provide several examples based on a wide range of models. We document and discuss the performance gains from using rwolf over other multiple-testing procedures that control the familywise error rate.


2015 ◽  
Vol 14 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Rosa J. Meijer ◽  
Thijmen J.P. Krebs ◽  
Jelle J. Goeman

AbstractWe present a multiple testing method for hypotheses that are ordered in space or time. Given such hypotheses, the elementary hypotheses as well as regions of consecutive hypotheses are of interest. These region hypotheses not only have intrinsic meaning but testing them also has the advantage that (potentially small) signals across a region are combined in one test. Because the expected number and length of potentially interesting regions are usually not available beforehand, we propose a method that tests all possible region hypotheses as well as all individual hypotheses in a single multiple testing procedure that controls the familywise error rate. We start at testing the global null-hypothesis and when this hypothesis can be rejected we continue with further specifying the exact location/locations of the effect present. The method is implemented in the


2021 ◽  
pp. 089198872110064
Author(s):  
Kevin Duff ◽  
Jian Ying ◽  
Kayla R. Suhrie ◽  
Bonnie C.A. Dalley ◽  
Taylor J. Atkinson ◽  
...  

Objective: Computerized cognitive training has been successful in healthy older adults, but its efficacy has been mixed in patients with amnestic Mild Cognitive Impairment (MCI). Methods: In a randomized, placebo-controlled, double-blind, parallel clinical trial, we examined the short- and long-term efficacy of a brain-plasticity computerized cognitive training in 113 participants with amnestic MCI. Results: Immediately after 40-hours of training, participants in the active control group who played computer games performed better than those in the experimental group on the primary cognitive outcome (p = 0.02), which was an auditory memory/attention composite score. There were no group differences on 2 secondary outcomes (global cognitive composite and rating of daily functioning). After 1 year, there was no difference between the 2 groups on primary or secondary outcomes. No adverse events were noted. Conclusions: Although the experimental cognitive training program did not improve outcomes in those with MCI, the short-term effects of the control group should not be dismissed, which may alter treatment recommendations for these patients.


2021 ◽  
Vol 17 (6) ◽  
pp. 445-453
Author(s):  
Angelina Vascimini, PharmD ◽  
Kevin Duane, PharmD ◽  
Stacey Curtis, PharmD

Objective: The opioid epidemic is frequently discussed including the staggering numbers involved with coprescribing opioids and benzodiazepines associated with death. Community pharmacists, with the help of a system intervention, have a unique opportunity to help reduce the coprescribing of benzodiazepines and opioids and reduce the associated risk of death.Design: A single center retrospective chart review was conducted after a system intervention was placed, as a quality improvement project, from November 2019 to May 2020.Setting: Independent community pharmacy.Patients/participants: Data included demographics, dosing of each medication pre- and post-intervention, and naloxone status.Main outcome(s) measures: The primary outcome evaluated was reduction in dose/discontinuation of these prescriptions. The secondary outcome evaluated was the number of naloxone prescriptions ordered per protocol and picked up.Results: The primary outcome did not show statistical difference; however, the secondary outcomes showed statistical significance.Conclusion: In conclusion, community pharmacists, with the help of evolving technologies, can reduce harm associated with the coprescribing of benzodiazepines and opioids.


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