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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 -
Medical Decision Making : An... Jan 2016Despite the benefits of the placebo-controlled trial design, it is limited by its inability to quantify total benefits and harms. Such trials, for example, are not...
BACKGROUND
Despite the benefits of the placebo-controlled trial design, it is limited by its inability to quantify total benefits and harms. Such trials, for example, are not designed to detect an intervention's placebo or nocebo effects, which if detected could alter the benefit-to-harm balance and change a decision to adopt or reject an intervention.
OBJECTIVE
In this article, we explore scenarios in which alternative experimental trial designs, which differ in the type of control used, influence expected value across a range of pretest assumptions and study sample sizes.
METHOD
We developed a decision model to compare 3 trial designs and their implications for decision making: 2-arm placebo-controlled trial ("placebo-control"), 2-arm intervention v. do nothing trial ("null-control"), and an innovative 3-arm trial design: intervention v. do nothing v. placebo trial ("novel design"). Four scenarios were explored regarding particular attributes of a hypothetical intervention: 1) all benefits and no harm, 2) no biological effect, 3) only biological effects, and 4) surreptitious harm (no biological benefit or nocebo effect).
RESULTS
Scenario 1: When sample sizes were very small, the null-control was preferred, but as sample sizes increased, expected value of all 3 designs converged. Scenario 2: The null-control was preferred regardless of sample size when the ratio of placebo to nocebo effect was >1; otherwise, the placebo-control was preferred. Scenario 3: When sample size was very small, the placebo-control was preferred when benefits outweighed harms, but the novel design was preferred when harms outweighed benefits. Scenario 4: The placebo-control was preferred when harms outweighed placebo benefits; otherwise, preference went to the null-control.
LIMITATIONS
Scenarios are hypothetical, study designs have not been tested in a real-world setting, blinding is not possible in all designs, and some may argue the novel design poses ethical concerns.
CONCLUSIONS
We identified scenarios in which alternative experimental study designs would confer greater expected value than the placebo-controlled trial design. The likelihood and prevalence of such situations warrant further study.
Topics: Control Groups; Decision Making; Double-Blind Method; Humans; Placebos; Randomized Controlled Trials as Topic; Single-Blind Method
PubMed: 25977361
DOI: 10.1177/0272989X15584770 -
Annals of the Rheumatic Diseases Dec 2008To examine the placebo effect and its potential determinants in the treatment of osteoarthritis (OA) via a systematic literature search of Medline, EMBASE, Scientific... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To examine the placebo effect and its potential determinants in the treatment of osteoarthritis (OA) via a systematic literature search of Medline, EMBASE, Scientific Citation Index, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library.
METHODS
Randomised placebo controlled trials in OA were included. The placebo effect was defined as the overall change from baseline in the placebo group. It was estimated as the effect size (ES; the standard mean difference between baseline and endpoint) and this was compared with the ES obtained from untreated control. ES for pain was the primary outcome. Statistical pooling was undertaken as appropriate and 95% CIs were used for comparison. Quality of trials was assessed and potential determinants of placebo effect were examined using multiple regression analysis. The partial regression coefficient (beta) was used to present the adjusted size of the association.
RESULTS
We identified 198 trials with 193 placebo groups (16 364 patients) and 14 untreated control groups (1167 patients) that met our inclusion criteria. These included a range of therapies (non-pharmacological, pharmacological and surgical treatments). Placebo was effective at relieving pain (ES 0.51, 95% CI 0.46 to 0.55 for the placebo group and 0.03, 95% CI -0.13 to 0.18 for untreated control). Placebo was also effective at improving function and stiffness. The pain-relieving effect increased when the active treatment effect (beta=0.38, p<0.001), baseline pain (0.006, p=0.014) and sample size (0.001, p=0.004) increased, and when placebo was given through injections/needles (0.144, p=0.020).
CONCLUSION
Placebo is effective in the treatment of OA, especially for pain, stiffness and self-reported function. The size of this effect is influenced by the strength of the active treatment, the baseline disease severity, the route of delivery and the sample size of the study.
Topics: Aged; Female; Humans; Injections, Intra-Articular; Male; Middle Aged; Osteoarthritis; Pain Measurement; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 18541604
DOI: 10.1136/ard.2008.092015 -
Current Opinion in Investigational... Jul 2010Evaluating the efficacy of a drug therapy in the acute and prophylactic treatment of migraine requires the conduct of placebo-controlled, randomized clinical trials. In...
Evaluating the efficacy of a drug therapy in the acute and prophylactic treatment of migraine requires the conduct of placebo-controlled, randomized clinical trials. In order to plan and conduct these studies in the most appropriate manner, it is desirable to know which factors influence the placebo response. This editorial overview discusses the factors that influence placebo response in trials for migraine and other headaches; such factors include expectation, blinding, route of drug administration, patient age and gender, and geographic distribution of the trials. The placebo response rates in the treatment of acute headache episodes are higher than in headache prophylaxis, and invasive procedures, such as injections, have a higher placebo response compared with orally administered drugs.
Topics: Adolescent; Adult; Child; Clinical Trials as Topic; Headache; Humans; Migraine Disorders; Placebo Effect; Placebos
PubMed: 20597189
DOI: No ID Found -
Developing World Bioethics Dec 2022This article analyzes the bioethical implications of using a control/placebo group when conducting clinical trials (CTs) investigating the treatment of periodontitis....
This article analyzes the bioethical implications of using a control/placebo group when conducting clinical trials (CTs) investigating the treatment of periodontitis. For this, the deductive method was used, proposing the interrelation of values, and a scoping systematic review was carried out. A total of 53% of the CTs reviewed were performed in low- and middle-income (LMI) countries, and 92% used a control/placebo group as a comparison group. Although there is a gold standard for the adjunctive treatment of periodontitis, the research ethics committees of most of the analyzed studies approved the use of control/placebo groups for the performance of CTs that did not explore new therapeutic alternatives. In some cases, the CT protocols were not approved by ethics committees, nor was informed consent used. In the LMI countries, a shorter period of recruitment was observed for patients who attended universities and public hospitals. Likewise, most of the CTs reviewed had public funding, a significant amount of which came from the pharmaceutical industry. Only one CT reported the low economic and educational level of its participants. Furthermore, none of the authors of the reviewed CTs declared conflicts of interest. Although the axiology of techno-science always takes into account at least the epistemic, technical and economic value systems, the hegemony of the economic values imposed by the pharmaceutical industry is evident in the performance of CTs investigating the treatment of periodontitis in LMI countries.
Topics: Humans; Control Groups; Developing Countries; Ethics Committees, Research; Informed Consent; Periodontitis
PubMed: 34498369
DOI: 10.1111/dewb.12334 -
International Review of Neurobiology 2020Throughout the history of medicine, multiple conceptions of "placebo" and "placebo effect" have often co-existed across different domains, and today the meaning of these... (Review)
Review
Throughout the history of medicine, multiple conceptions of "placebo" and "placebo effect" have often co-existed across different domains, and today the meaning of these concepts is still disputed. Against this background, this chapter provides a succinct account of the key events in the history of the concepts of "placebo," "placebo control," and "placebo effect." The first section reconstructs the etymology of the term "placebo" and its first introduction in medicine. The next sections provide an account of how placebos have been employed in both medical practice and scientific research in modern medicine. Later sections trace the emergence of the concepts of "placebo control" and "placebo effect" in the first half of the 20th century, from the first empirical studies investigating the effects of placebos up to the publication of Beecher's landmark article "The Powerful Placebo." Finally, the last two sections review the varieties of randomized, placebo-controlled trials (RCTs) in the second half of the 20th century, and the subsequent wave of empirical studies that, starting from the 1970s, have investigated the psychological, pharmacological and neurobiological mechanisms of placebo effects.
Topics: Biomedical Research; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Placebo Effect; Placebos; Randomized Controlled Trials as Topic
PubMed: 32563292
DOI: 10.1016/bs.irn.2020.03.028 -
Medical Hypotheses May 2010Just as a placebo can mimic an immediately effective drug so chronic drug dependence may mimic an effective long-term or preventive treatment. The discovery of the...
Covert drug dependence should be the null hypothesis for explaining drug-withdrawal-induced clinical deterioration: the necessity for placebo versus drug withdrawal trials on normal control subjects.
Just as a placebo can mimic an immediately effective drug so chronic drug dependence may mimic an effective long-term or preventive treatment. The discovery of the placebo had a profound result upon medical practice, since it became recognized that it was much harder to determine the therapeutic value of an intervention than was previously assumed. Placebo is now the null hypothesis for therapeutic improvement. As David Healy describes in the accompanying editorial on treatment induced stress syndromes [1], an analogous recognition of the effect of drug dependence is now overdue. Drug dependence and withdrawal effects should in future become the null hypothesis when there is clinical deterioration following cessation of treatment. The ideal methodology for detecting drug dependence and withdrawal is a double-blind placebo controlled and randomized trial using disease-free normal control subjects. Normal controls are necessary to ensure that the possibility of underlying chronic disease is eliminated: so long as subjects begin the trial as 'normal controls' it is reasonable to infer that any clinical or psychological problems (above placebo levels) which they experience following drug withdrawal can reasonably be attributed to the effects of the drug. This is important because the consequences of failing to detect the risk of covert drug dependence may be considerably worse than failing to detect a placebo effect. Drug dependent patients not only fail to receive benefit and suffer continued of inconvenience, expense and side effects; but the drug has actually created and sustained a covert chronic pathology. However, the current situation for drug evaluation is so irrational that it would allow chronic alcohol treatment to be regarded as a cure for alcoholism on the basis that delirium tremens follows alcohol withdrawal and alcohol can be used to treat delirium tremens! Therefore, just as placebo controlled trials of drugs are necessary to detect ineffective drugs, so drug withdrawal trials on normal control subjects should be regarded as necessary to detect dependence-producing drugs.
Topics: Control Groups; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 20223602
DOI: 10.1016/j.mehy.2010.02.015 -
Canadian Journal of Psychiatry. Revue... May 1995
Topics: Control Groups; Dissent and Disputes; Ethics, Medical; Group Processes; Humans; Placebos; Randomized Controlled Trials as Topic
PubMed: 7621384
DOI: 10.1177/070674379504000401 -
Current Allergy and Asthma Reports May 2007The placebo is much more than a control medicine in a clinical trial. The placebo response is the largest component of any allergy treatment and consists of two... (Review)
Review
The placebo is much more than a control medicine in a clinical trial. The placebo response is the largest component of any allergy treatment and consists of two components: nonspecific effects (eg, natural recovery) and a "true placebo effect" that is the psychological therapeutic effect of the treatment. Belief in the beneficial nature of the treatment is a key component of the true placebo effect, and can be enhanced by factors such as interaction with the physician and the sensory impact of the treatment. Negative beliefs can generate a nocebo effect that may explain some psychogenic illnesses; this is the basis of much research in psychoneuroimmunology. An understanding of the placebo and nocebo effects is important for general allergy practice, and harnessing the power of the true placebo effect is a major challenge to modern medicine.
Topics: Attitude to Health; Clinical Trials as Topic; Control Groups; Humans; Hypersensitivity; Physician-Patient Relations; Placebo Effect; Placebos; Psychophysiologic Disorders; Suggestion
PubMed: 17437679
DOI: 10.1007/s11882-007-0006-2 -
Lancet (London, England)
Topics: Anti-HIV Agents; Control Groups; Controlled Clinical Trials as Topic; Drug Administration Schedule; Ethics, Medical; Ethiopia; Female; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Internationality; Placebos; Pregnancy; Pregnant Women; Therapeutic Human Experimentation; Zidovudine
PubMed: 9428264
DOI: 10.1016/S0140-6736(05)63659-8