scholarly journals Using Observational Study Data as an External Control Group for a Clinical Trial: an Empirical Comparison of Methods to Account for Longitudinal Missing Data

2022 ◽  
Author(s):  
Vibeke Norvang ◽  
Espen A. Haavardsholm ◽  
Sara K. Tedeschi ◽  
Houchen Lyu ◽  
Joseph Sexton ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Missing Data ◽  
Observational Study ◽  
Observational Data ◽  
Outcome Data ◽  
Drop Out ◽  
External Control ◽  
Control Group ◽  
Multicenter Studies ◽  
Similar Treatment

Abstract Background: Observational data are increasingly being used to conduct external comparisons to clinical trials. In this study, we empirically examined whether different methodological approaches to longitudinal missing data affected study conclusions in this setting. Methods: We used data from one clinical trial and one prospective observational study, both Norwegian multicenter studies including patients with recently diagnosed rheumatoid arthritis and implementing similar treatment strategies, but with different stringency. A binary disease remission status was defined at 6, 12, and 24 months in both studies. After identifying patterns of longitudinal missing outcome data, we evaluated the following five approaches to handle missingness: analyses of patients with complete follow-up data, multiple imputation (MI), inverse probability of censoring weighting (IPCW), and two combinations of MI and IPCW. Results: We found a complex non-monotone missing data pattern in the observational study (N=328), while missing data in the trial (N=188) was monotone due to drop-out. In the observational study, only 39.0% of patients had complete outcome data, compared to 89.9% in the trial. All approaches to missing data indicated favorable outcomes of the treatment strategy in the trial and resulted in similar study conclusions. Variations in results across approaches were mainly due to variations in estimated outcomes for the observational data. Conclusions: Five different approaches to handle longitudinal missing data resulted in similar conclusions in our example. However, the extent and complexity of missing observational data affected estimated comparative outcomes across approaches, highlighting the need for careful consideration of methods to account for missingness when using observational data as external controls to trial data.

scholarly journals Analysing and reporting of observational data: a systematic review informing the EULAR points to consider when analysing and reporting comparative effectiveness research with observational data in rheumatology

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001818
Author(s):  
Kim Lauper ◽  
Joanna Kedra ◽  
Maarten de Wit ◽  
Bruno Fautrel ◽  
Thomas Frisell ◽  
...  
Keyword(s):  
Missing Data ◽  
Observational Data ◽  
Comparative Effectiveness Research ◽  
Comparative Effectiveness ◽  
Drop Out ◽  
Effectiveness Research ◽  
Confounding Factors ◽  
Drug Effectiveness ◽  
Ovid Medline ◽  
Number Of Patients

ObjectivesTo evaluate the analysis and reporting of comparative effectiveness research with observational data in rheumatology, informing European Alliance of Associations for Rheumatology points to consider.MethodsWe performed a systematic literature review searching Ovid MEDLINE for original articles comparing drug effectiveness in longitudinal observational studies, published in key rheumatology journals between 2008 and 2019. The extracted information focused on reporting and types of analyses. We evaluated if year of publication impacted results.ResultsFrom 9969 abstracts reviewed, 211 articles fulfilled the inclusion criteria. Ten per cent of studies did not adjust for confounding factors. Some studies did not explain how they chose covariates for adjustment (9%), used bivariate screening (21%) and/or stepwise selection procedures (18%). Only 33% studies reported the number of patients lost to follow-up and 25% acknowledged attrition (drop-out or treatment cessation). To account for attrition, studies used non-responder imputation, followed by last observation carried forward (LOCF) and complete case (CC) analyses. Most studies did not report the number of missing data on covariates (83%), and when addressed, 49% used CC and 11% LOCF. Date of publication did not influence the results.ConclusionMost studies did not acknowledge missing data and attrition, and a tenth did not adjust for any confounding factors. When attempting to account for them, several studies used methods which potentially increase bias (LOCF, CC analysis, bivariate screening…). This study shows that there is no improvement over the last decade, highlighting the need for recommendations for the assessment and reporting of comparative drug effectiveness in observational data in rheumatology.

scholarly journals Intravenous Immunoglobulin Gamma for Severe Cases of Coronavirus Disease of 2019: A Randomized Placebo-Controlled Double-Blinded Clinical Trial

2020 ◽  
Author(s):  
Naser Gharebaghi ◽  
Rahim Nejadrahim ◽  
Seyed Jalil Mousavi ◽  
Seyyed-Reza Sadat-Ebrahimi ◽  
Reza Hajizadeh
Keyword(s):  
Clinical Trial ◽  
Mortality Rate ◽  
Hospital Mortality ◽  
Intravenous Immunoglobulin ◽  
Initial Treatment ◽  
Control Group ◽  
Multicenter Studies ◽  
Infected People ◽  
Laboratory Test Results ◽  
Double Blinded

Abstract Background: Coronavirus disease of 2019 (COVID-19) with high-transmission power has infected people in many countries around the world. Discovering an effective medication for the treatment of this disease, especially in severe cases, has become the subject of intense scientific investigations. Therefore, the objective of this study was to evaluate the efficacy of intravenous immunoglobulin (IVIg) in patients with severe COVID-19 infection.Methods: The study was conducted as a randomized placebo-controlled double-blinded clinical trial. Fifty-nine patients with severe COVID-19 infection who did not respond to initial treatment were randomly assigned into two groups. One group received IVIg (human) four vials every day for three days in addition to initial treatment, and the other group received placebo. Patients’ demographic, clinical, and selected laboratory test results, as well as the occurrence of in-hospital mortality, were recorded. Result: Among included patients, 30 patients received IVIg and 29 patients received placebo. Demographics, clinical characteristics and evaluated laboratory tests of two groups were not statistically different (P>0.05). The in-hospital mortality rate was significantly lower in the IVIg group as compared to the control group (6 [20.0%] vs 14 [48.3%], respectively, p = 0.022). Multivariate regression analysis demonstrated that administration of IVIg had a significant impact on mortality rate (aOR= 0.003 [95%CI: 0.001 - 0.815], p=0.042).Conclusion: Our study was the first randomized double-blinded study that demonstrated that the administration of IVIg in patients with severe COVID-19 infection who did not respond to initial treatment could improve their clinical outcome and reduce the mortality rate. However, further multicenter studies with larger samples size are required to confirm the applicability of using this medication as the standard treatment.Trial registration: The study protocol is registered at the Iranian Registry of Clinical Trials (www.IRCT.ir) with the registration number of IRCT20200501047259N1. Registered 17 May 2020. Retrospectively registered.

Efficacy of Aloe vera/ Plantago Major Gel in Diabetic Foot Ulcer: A Randomized Double-Blind Clinical Trial

2019 ◽  
Vol 16 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Younes Najafian ◽  
Zahra M. Khorasani ◽  
Mona N. Najafi ◽  
Shokouh S. Hamedi ◽  
Marjan Mahjour ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Diabetic Foot ◽  
Intervention Group ◽  
Aloe Vera ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Control Group ◽  
Plantago Major ◽  
Double Blind ◽  
Significant Difference

Background:Diabetic foot ulcer (DFU) is one of the most common complications of diabetic patients. Mostly, non-healing DFU leads to infection, gangrene, amputation and even death. High costs and poor healing of the wounds need a new treatment such as alternative medicine. So, the aim of this study was to evaluate the efficacy of Aloe vera/ Plantago major gel (Plantavera gel) in healing of DFUMethods:Forty patients with DFU enrolled in a double-blind randomized clinical trial. The patients who were randomly assigned into the intervention group (n = 20), received topical Plantavera gel in addition to the routine cares, whereas the patients in the control group (n = 20), received topical Placebo gel in addition to the routine cares. Intervention was done twice a day for 4 weeks in the both groups. Photography and an evaluation of DFU healing were conducted by a checklist and then were scored at baseline and at the end of each week. The collected data was analyzed by SPSS software.Results:At the end of the study, there was a significant difference between the two groups in terms of total ulcer score (P<0.001) and Plantavera gel significantly reduced the ulcer surface comparing with the control group (P=0.039). However, there was not a significant difference between the two groups (P=0.263) in terms of the ulcer depth. During this study, no side effect was observed for Plantavera gel in the intervention group.Conclusion:Topical Plantavera gel seems to be an effective, cheap and safe treatment. Of course, further studies are required to confirm the properties of the wound healing of this gel.

scholarly journals Effects of a positive thinking program on hope and sleep quality in Iranian patients with thalassemia: a randomized clinical trial

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Somayeh Makaremnia ◽  
Marieh Dehghan Manshadi ◽  
Zahra Khademian
Keyword(s):  
Clinical Trial ◽  
Sleep Quality ◽  
Training Program ◽  
Randomized Clinical Trial ◽  
Thalassemia Major ◽  
Trial Registration ◽  
Control Group ◽  
Positive Thinking ◽  
Experimental Group

Abstract Background Thalassemia have a negative impact on the patients' psychological health and sleep quality. This study aimed to determine the effects of a positive thinking training program on hope and sleep quality of patients with thalassemia major. Methods This randomized clinical trial was conducted on 78 patients with thalassemia major including 36 males (46.2%) and 42 females (53.8%) with a mean age of 25.56 ± 29.6 in Iran. Subjects were randomly assigned into experimental and control groups. Experimental group received 16 h training based on positive thinking materials published by Martin Seligman. Control group received only usual programs. Data were collected at baseline, as well as immediately and one month after the intervention, using Snyder’s Hope Scale and the Pittsburgh Sleep Quality Index. Data analysis was performed using SPSS Software 18.0; statistical tests included the independent T-test, the Chi-square, Mann Whitney, and Friedman test. Significance level was set at 0.05 in this study. Results The experimental group had a significantly higher mean hope score compared to the control group immediately (45.38 ± 7.82 vs. 35.32 ± 5.54, P < 0.001) and one month following intervention (44.67 ± 3.47 vs. 35 ± .54, P < 0.001). Moreover, the mean sleep quality scores of the experimental group was significantly greater than that for control group immediately (5.35 ± 2.02 vs. 7 ± 2.4, P = 0.004) and one month after the intervention (4.23 ± 2.2 vs.7.02 ± 3.03, P < 0.001). Conclusion Since our training program on positive thinking improved hope and quality of sleep in patients with thalassemia major, we recommend the use of such courses as an important step toward promotion of hope and sleep quality among these patients. Trial registration The name of the registry: Iranian Registry of Clinical Trials. Trial Registration Number: IRCT2017010431774N1. URL of the trial registry record: https://en.irct.ir/trial/24923. Registration Date: 07/03/2017.

scholarly journals Evaluation of the online-based self-help programme “Selfapy” in patients with unipolar depression: study protocol for a randomized, blinded parallel group dismantling study

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rico Krämer ◽  
Stephan Köhler
Keyword(s):  
Depressive Symptoms ◽  
Depression Scale ◽  
Drop Out ◽  
Control Group ◽  
Hamilton Depression Scale ◽  
Online Interventions ◽  
Phone Calls ◽  
Self Help ◽  
Low Threshold ◽  
The Impact

Abstract Background Patients with mild to moderate depressive symptoms can have limited access to regular treatment; to ensure appropriate care, low-threshold treatment is needed. Effective online interventions could increase the supply of low-threshold treatment. Further research is needed to evaluate the effectiveness of online interventions. This study aims to evaluate the online-based self-help programme “Selfapy” on a sample of depressive subjects and compares the impact of the programme’s unaccompanied version with its therapeutic accompanied version. Methods A sample of 400 subjects that have a mild to severe depressive episode (Becks Depression Inventory - II and Hamilton Depression Scale) will be used. Subjects are randomly assigned to immediate access to an unaccompanied course (no support from psychologist via weekly phone calls), immediate access to an accompanied course (support from a psychologist via weekly phone calls) or a waiting list control group (access to the intervention after 24 weeks). The intervention will last for a period of 12 weeks. Depressive symptoms as a primary parameter, as well as various secondary parameters, such as life satisfaction, therapeutic relationships, social activation, self-esteem, attitudes towards Internet interventions and drop-out rates, are recorded at four different points in time: at baseline (T1), 6 weeks after the start of the intervention (T2), 12 weeks after the start of the intervention (T3) and 3 months after completion of the treatment follow-up (T4). Conclusion This randomized and controlled, blinded study will make use of a “dismantled” approach to adequately compare the accompanied and unaccompanied versions of the intervention. Positive and meaningful results are expected that could influence the acceptance and implementation of online interventions. Trial registration German Clinical Trials Register DRKS00017191. Registered on 14 June 2019

scholarly journals Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandra Rajewska-Rager ◽  
Monika Dmitrzak-Weglarz ◽  
Pawel Kapelski ◽  
Natalia Lepczynska ◽  
Joanna Pawlak ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Calcium Binding ◽  
Clinical Symptoms ◽  
Small Sample Size ◽  
Serum Levels ◽  
Small Sample ◽  
Drop Out ◽  
Control Group ◽  
Longitudinal Assessment ◽  
Depressed Group

AbstractMood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

scholarly journals Efficacy and safety of duloxetine for postoperative pain after total knee arthroplasty in centrally sensitized patients: study protocol for a randomized controlled trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shicheng Wang ◽  
Wensheng Wang ◽  
Long Shao ◽  
Jing Ling
Keyword(s):  
Clinical Trial ◽  
Total Knee Arthroplasty ◽  
Randomized Controlled Trial ◽  
Pain Control ◽  
Controlled Trial ◽  
Control Group ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Total Knee ◽  
Postoperative Residual

Abstract Background Postoperative residual knee pain after total knee arthroplasty (TKA) is a significant factor that contributes to patient dissatisfaction. Patients with preoperative central sensitization (CS) may be more susceptible to unexplained chronic pain after TKA, and duloxetine has been reported to be effective in post-TKA pain control in patients with CS. However, there remains limited evidence to support this off-label use in routine clinical practice. Hence, we designed this randomized, placebo-controlled, triple-blind clinical trial to evaluate the effects of preoperative screening and targeted duloxetine treatment of CS on postoperative residual pain compared with the care-as-usual control group. Methods This randomized controlled trial includes patients with knee osteoarthritis on a waiting list for primary unilateral TKA. Patients with preoperative CS will be randomly allocated to the perioperative duloxetine treatment group (duloxetine group) or the care-as-usual control group (placebo group). Patients in the duloxetine group will receive a half-dose of preemptive duloxetine (30 mg/day) for a week before surgery and a full-dose of duloxetine (60 mg/day) for six weeks after surgery. The primary outcome is the intensity of residual pain at six months after TKA, including the visual analogue scale, 11-point numeric rating scale, the sensory dimension of the brief pain inventory, and the pain subscale of the Knee injury and Osteoarthritis Outcome Score. The secondary outcome measures will include the pain and function related outcomes. All of the patients will be followed up at one, three, and six months after surgery. All adverse events will be recorded and immediately reported to the primary investigator and ethics committee to decide if the patient needs to drop out from the trial. Discussion This clinical trial will convey the latest evidence of the efficacy and safety of the application of duloxetine in postoperative pain control in CS patients who are scheduled for TKA. The study results will be disseminated at national and international conferences and published in peer-reviewed journals. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn) registration number: ChiCTR2000031674. Registered 07 April 2020.

scholarly journals Intraoperative protective ventilation in patients undergoing major neurosurgical interventions: a randomized clinical trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Federico Longhini ◽  
Laura Pasin ◽  
Claudia Montagnini ◽  
Petra Konrad ◽  
Andrea Bruni ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Outcome ◽  
Adverse Events ◽  
Respiratory Rate ◽  
Randomized Clinical Trial ◽  
Protective Ventilation ◽  
Adult Patients ◽  
Control Group ◽  
Neurosurgical Procedures ◽  
Neurosurgical Patients

Abstract Background Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. Methods This single-centre, pilot randomized clinical trial was conducted at the University Hospital “Maggiore della Carità” (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6–8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. Results A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. Conclusions LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. Trial registration registered on the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au), registration number ACTRN12615000707561.

scholarly journals The control of pain due to dentin hypersensitivity in individuals with molar–incisor hypomineralisation: a protocol for a randomised controlled clinical trial

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e044653
Author(s):  
Ana Paula Taboada Sobral ◽  
Elaine Marcilio Santos ◽  
Ana Cecilia Aranha ◽  
Paulo Vinícius Soares ◽  
Caroline Moraes Moriyama ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tooth Enamel ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Dentin Hypersensitivity ◽  
Molar Incisor Hypomineralisation ◽  
Randomised Controlled Clinical Trial ◽  
Sensitive Teeth ◽  
Randomised Controlled ◽  
Incisor Hypomineralisation

IntroductionDentin hypersensitivity (DH) is defined as high sensitivity of the vital dentin when exposed to thermal, chemical or tactile stimuli. Two mechanisms are required for the occurrence of DH: (1) the dentin must be exposed and (2) the dentinal tubules must be open and connected to the pulp. Molar–incisor hypomineralisation (MIH) is a qualitative abnormality of a genetic origin that affects tooth enamel and, in most cases, is accompanied by DH. The control of tooth sensitivity is fundamental to the successful treatment of MIH. The aim of the proposed randomised, controlled, clinical trial is to evaluate the effectiveness of different protocols for the control of DH in patients with teeth affected by MIH.Methods and analysisOne hundred and forty patients who meet the inclusion criteria will be allocated to four groups. Group 1 will be the control group (placebo). In Group 2, sensitive teeth will be sealed with PermaSeal (Ultradent). In Group 3, sensitive teeth will receive low-level laser (LLL, AsGaAl) at a wavelength of 780 nm (Laser XT Therapy, DMC, São Carlos, Brazil). In Group 4, sensitive teeth will be treated with both LLL and PermaSeal (Ultradent). DH will be evaluated 15 min after the application of the treatments and the patients will be reevaluated 1 week, 1 month, 3 months and 6 months after the treatments. The primary outcome of this study is change in pain/sensitivity, when evaluated through a Visual Analogue Scale, to determine the effectiveness of the proposed treatments, as well as differences among the evaluation times for each proposed treatment.Ethics and disseminationThis protocol has been ethically approved by the local medical ethical committee (protocol number: 4.020.261). Results will be submitted to international peer-reviewed journals and presented at international conferences.Trial registration numberNCT04407702.

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