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Journal of Clinical Epidemiology Jul 2017Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of... (Review)
Review
OBJECTIVES
Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo.
STUDY DESIGN AND SETTING
An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress).
RESULTS
The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect.
CONCLUSION
Pharmacological active placebo control interventions are rarely used in randomized clinical trials, but they constitute a methodological tool which merits serious consideration. We suggest that active placebos are used more often in trials of drugs with noticeable side effects, especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high.
Topics: Control Groups; Humans; Pharmaceutical Preparations; Placebo Effect; Randomized Controlled Trials as Topic; Research Design
PubMed: 28342907
DOI: 10.1016/j.jclinepi.2017.03.001 -
Comprehensive Physiology Apr 2012Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers:... (Review)
Review
Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause versus treatment; physical activity and inactivity mechanisms differ; gene-environment interaction (including aerobic training adaptations, personalized medicine, and co-twin physical activity); and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, nonalcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, pre-eclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life.
Topics: Adaptation, Physiological; Chronic Disease; Exercise; Gene-Environment Interaction; Humans; Metabolic Syndrome; Motor Activity; Pharmacogenetics; Physical Fitness; Risk Factors; Sedentary Behavior; Twin Studies as Topic
PubMed: 23798298
DOI: 10.1002/cphy.c110025 -
Nutricion Hospitalaria Sep 2013The benefits of regular physical activity have been known since ancient Greek. But in the last Century the scientific knowledge around this topic has progressed... (Review)
Review
The benefits of regular physical activity have been known since ancient Greek. But in the last Century the scientific knowledge around this topic has progressed enormously, starting with the early studies of JN Morris and RS Paffenberger, who demonstrated that physical activity at work reduced incidence of cardiovascular disease and mortality. In the Harvard alumni study, the lowest risk was associated with a weekly output of 1000 to 2000 kcal performing vigorous activities. Further studies in all age groups have supported these findings and have added that even moderate levels of physical activity provide considerable benefits to health, including lower prevalence of overweight and obesity at all ages. Metabolic fat oxidation rate is highest at exercise intensities between 45 and 65% of VO2max. This means that people must be active regularly and force physiological mechanisms at certain intensities. All this body of evidence has contributed to current WHO physical activity recommendations of 150 min/week of moderate to vigorous physical activity (MVPA) in adults and elderly, and 60 min/day of MVPA in children and adolescents, with additional strength training, apart from adopting an active lifestyle. In the last 50 years, occupational physical activity has been reduced for about 120 kcal/day, and sedentarism has emerged as an additional risk factor to physical inactivity. Even if less than 60 min of TV time in adults have been related to lower average BMI, there is still a need for research to determine the appropriate dose of exercise in combination with sedentary behaviours and other activities in the context of our modern lifestyle in order to prevent obesity at all ages. As public health measures have failed to stop the obesity epidemic in the last 3 decades, there is clearly a need to change the paradigm. The inclusion of sport scientists, physical education teachers and other professionals in the multidisciplinary team which should be responsible for drawing the road map to prevent the increase of the obesity epidemic effectively is a "must" from our point of view.
Topics: Adult; Cardiovascular Diseases; Child; Health Status; Humans; Life Style; Motor Activity; Obesity; Sedentary Behavior; Sports
PubMed: 24010748
DOI: 10.3305/nh.2013.28.sup5.6923 -
Alternative Therapies in Health and... Sep 2023The selection of a control group should foremost be determined by the study's primary intended outcome and trial design. When examining the effects of the physical... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
The selection of a control group should foremost be determined by the study's primary intended outcome and trial design. When examining the effects of the physical movements that comprise yoga postures, an active control group, with physical exercise as the control, is often recommended.
OBJECTIVE
The current study aimed to define an active control group that participates in physical exercise, emphasizing the importance of matching the exercise's volume to that of an intervention group's yoga, and to provide a tangible example from a federally funded, recently completed, randomized controlled trial.
DESIGN
The research team designed a control group, providing a case study as a example of it.
SETTING
The study took place at Colorado State University.
INTERVENTION
The exercise component for the control group included 60 minutes of low-intensity exercise, matched with 60 minutes of Hatha yoga for the intervention group. Because the intervention included chronic pain self-management in addition to the exercise component, the education component for the control group included 45 minutes of group-based, general health-and-wellness education and discussion.
CONCLUSIONS
Future randomized trials for yoga and other complementary or integrative health interventions should continue to use appropriate active control groups, which will serve to enhance the scientific rigor of conclusions that can be drawn with respect to the effectiveness of these interventions.
Topics: Humans; Yoga; Control Groups; Exercise; Physical Therapy Modalities
PubMed: 35687710
DOI: No ID Found -
PM & R : the Journal of Injury,... Nov 2012After obesity rates in youth reached alarming rates, public health officials recognized the need for specific physical activity guidelines for children and adolescents.... (Review)
Review
After obesity rates in youth reached alarming rates, public health officials recognized the need for specific physical activity guidelines for children and adolescents. Numerous health care groups and sports and fitness organizations collaborated on the development of the Physical Activity Guidelines for Americans in 2008, which have been widely endorsed and include recommendations for the pediatric population. Children and adolescents should participate in moderate-to-vigorous physical activity 1 or more hours per day and muscle and bone-strengthening activities 3 or more times per week. Physical activities should be age appropriate, enjoyable, and varied and occur beyond what is required for typical activities of daily living. Adequate exercise in youth improves strength, cardiorespiratory fitness, and body composition and therefore decreases cardiovascular risk factors. An improved cardiovascular profile provides a continued benefit in adulthood. Exercise also improves bone health, psychological well-being, cognition, and school performance and may decrease the risk of sports injury. Exercise habits established in childhood often continue into adulthood.
Topics: Adolescent; Body Composition; Bone Density; Cardiovascular Physiological Phenomena; Child; Executive Function; Health Behavior; Health Promotion; Humans; Mental Health; Motor Activity; Muscle Stretching Exercises; Obesity; Oxygen Consumption; Physical Fitness; Practice Guidelines as Topic; Range of Motion, Articular; Resistance Training; Respiratory Physiological Phenomena
PubMed: 23174545
DOI: 10.1016/j.pmrj.2012.09.585 -
Exercise and Sport Sciences Reviews Oct 2019The corpus callosum is an important neural structure for controlling and coordinating bilateral movements of the upper limbs; however, there remains a substantial lack... (Review)
Review
The corpus callosum is an important neural structure for controlling and coordinating bilateral movements of the upper limbs; however, there remains a substantial lack of knowledge regarding its association with lower limb control. We argue that transcallosal structure is an integral neural mechanism underlying control of the lower limbs and callosal degradation is a key contributor to mobility declines.
Topics: Accidental Falls; Aging; Corpus Callosum; Gait Analysis; Humans; Lower Extremity; Motor Activity; Walking
PubMed: 31525166
DOI: 10.1249/JES.0000000000000202 -
The International Journal of Behavioral... Jul 2017Well-designed research trials are critical for determining the efficacy and effectiveness of nutrition education interventions. To determine whether behavioral and/or... (Review)
Review
BACKGROUND
Well-designed research trials are critical for determining the efficacy and effectiveness of nutrition education interventions. To determine whether behavioral and/or cognition changes can be attributed to an intervention, the experimental design must include a control or comparison condition against which outcomes from the experimental group can be compared. Despite the impact different types of control groups can have on study outcomes, the treatment provided to participants in the control condition has received limited attention in the literature.
METHODS
A systematic review of control groups in nutrition education interventions was conducted to better understand how control conditions are described in peer-reviewed journal articles compared with experimental conditions. To be included in the systematic review, articles had to be indexed in CINAHL, PubMed, PsycINFO, WoS, and/or ERIC and report primary research findings of controlled nutrition education intervention trials conducted in the United States with free-living consumer populations and published in English between January 2005 and December 2015. Key elements extracted during data collection included treatment provided to the experimental and control groups (e.g., overall intervention content, tailoring methods, delivery mode, format, duration, setting, and session descriptions, and procedures for standardizing, fidelity of implementation, and blinding); rationale for control group type selected; sample size and attrition; and theoretical foundation.
RESULTS
The search yielded 43 publications; about one-third of these had an inactive control condition, which is considered a weak study design. Nearly two-thirds of reviewed studies had an active control condition considered a stronger research design; however, many failed to report one or more key elements of the intervention, especially for the control condition. None of the experimental and control group treatments were sufficiently detailed to permit replication of the nutrition education interventions studied.
CONCLUSIONS
Findings advocate for improved intervention study design and more complete reporting of nutrition education interventions.
Topics: Control Groups; Diet; Health Education; Humans; Research
PubMed: 28693581
DOI: 10.1186/s12966-017-0546-3 -
Brain Injury Oct 2020Interventions are needed to address chronic health conditions, such as obesity and diabetes, faced by adults with traumatic brain injury (TBI). The objective of this... (Review)
Review
PRIMARY OBJECTIVE
Interventions are needed to address chronic health conditions, such as obesity and diabetes, faced by adults with traumatic brain injury (TBI). The objective of this narrative is to present the justification for and an exemplar of an active attention control condition as a needed comparison group in clinical trials for intensive lifestyle interventions after TBI.
RESEARCH DESIGN
Narrative review.
METHODS AND PROCEDURES
N/A.
MAIN OUTCOMES AND RESULTS
Despite the historical use in scientific research, integration of appropriate control conditions to account for not only the placebo effect, but also to isolate the "active ingredients" of behavioural interventions, remains a challenge. This is particularly true for intensive lifestyle interventions, especially with the increasing use of mobile health (mHealth) to augment these interventions. Herein we describe the design, content, and implementation of a group-based, attention control condition, referred to as the Brain Health Group, as an exemplar active comparison to an intensive lifestyle intervention for weight-loss among individuals with TBI (GLB-TBI).
CONCLUSIONS
Intervention studies should incorporate strong scientific designs and active control conditions to assess effectiveness and aid in replication. Following recommended guidelines, we provide an active control condition for future group-based intensive lifestyle interventions post-TBI.
Topics: Adult; Attention; Brain Injuries; Control Groups; Humans; Life Style; Obesity
PubMed: 33001707
DOI: 10.1080/02699052.2020.1825807 -
Seminars in Arthritis and Rheumatism Aug 2021To assess how patient characteristics and study design influence the effectiveness of control interventions in hand OA trials. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess how patient characteristics and study design influence the effectiveness of control interventions in hand OA trials.
METHODS
The study protocol was registered in PROSPERO (CRD42020163473). Two authors independently searched four electronic databases from their inception to December 31, 2019. Randomized and non-randomized controlled hand OA trials were included if pain intensity was assessed using a validated scale. We allocated control groups into one of the following: placebo, add-on treatment, no treatment, or active treatment. The standardized mean differences (d) of pain, as well as subjective function and hand strength, were pooled with 95% confidence intervals (CI) and 90% prediction intervals using random-effects models. Meta-regression and post-hoc subgroup analyses were performed to investigate which factors potentially impacted placebo analgesia and between-study heterogeneity.
RESULTS
Thirty-one placebo, 11 add-on, 12 no-treatment, and 10 active-treatment controls were included in meta-analyses. Effective pain relief was observed in placebo (d = -0.50, 95% CI -0.63 to -0.37), add-on (d = -0.35, 95% CI -0.59 to -0.12), and active-treatment (d = -0.92, 95% CI -1.35 to -0.48) groups. In subjective function, these treatments had smaller but beneficial effects; hand strength, contrastingly, was not improved. Placebo effects were larger when flare designs were used (d = -0.96) and more homogeneous when minimum pain thresholds were set (d = -0.46, 90% prediction intervals -0.79 to -0.14).
CONCLUSION
Placebo, add-on, and active control treatments were more effective than the no treatment control in relieving hand pain and improving subjective function. By choosing minimum pain thresholds and flare requirements at patient enrollment, moderate pain relief may be replicated among control participants in future randomized placebo-controlled trials.
Topics: Control Groups; Hand; Humans; Osteoarthritis; Pain; Randomized Controlled Trials as Topic
PubMed: 34146952
DOI: 10.1016/j.semarthrit.2021.04.006 -
Current Opinion in HIV and AIDS Nov 2023Ending the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel... (Review)
Review
PURPOSE OF REVIEW
Ending the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.
RECENT FINDINGS
Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.
SUMMARY
Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.
Topics: Humans; HIV Infections; Control Groups; Research Design; Anti-Retroviral Agents; AIDS Vaccines; Randomized Controlled Trials as Topic
PubMed: 37712852
DOI: 10.1097/COH.0000000000000818