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BMJ Open Mar 2016To find evidence, either corroborating or refuting, for many persisting beliefs regarding the feasibility of carrying out surgical randomised controlled trials with a... (Review)
Review
OBJECTIVES
To find evidence, either corroborating or refuting, for many persisting beliefs regarding the feasibility of carrying out surgical randomised controlled trials with a placebo arm, with emphasis on the challenges related to recruitment, funding, anaesthesia or blinding.
DESIGN
Systematic review.
DATA SOURCES AND STUDY SELECTION
The analysis involved studies published between 1959 and 2014 that were identified during an earlier systematic review of benefits and harms of placebo-controlled surgical trials published in 2014.
RESULTS
63 trials were included in the review. The main problem reported in many trials was a very slow recruitment rate, mainly due to the difficulty in finding eligible patients. Existing placebo trials were funded equally often from commercial and non-commercial sources. General anaesthesia or sedation was used in 41% of studies. Among the reviewed trials, 81% were double-blinded, and 19% were single-blinded. Across the reviewed trials, 96% (range 50-100%) of randomised patients completed the study. The withdrawal rate during the study was similar in the surgical and in the placebo groups.
CONCLUSIONS
This review demonstrated that placebo-controlled surgical trials are feasible, at least for procedures with a lower level of invasiveness, but also that recruitment is difficult. Many of the presumed challenges to undertaking such trials, for example, funding, anaesthesia or blinding of patients and assessors, were not reported as obstacles to completion in any of the reviewed trials.
Topics: Anesthesia, General; Feasibility Studies; Humans; Placebos; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 27008687
DOI: 10.1136/bmjopen-2015-010194 -
Clinical Gastroenterology and... Dec 2014It is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn's disease (CD), to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
It is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn's disease (CD), to understand disease progression, and to calculate sample size. We conducted a systematic review and meta-analysis of rates of response to placebo in trials of patients with fistulizing CD.
METHODS
We searched MEDLINE, EMBASE, EMBASE CLASSIC, and the Cochrane central register of controlled trials for randomized controlled trials (RCTs) comparing pharmacologic agents with placebo in adults with fistulizing CD. We identified studies that reported complete fistula closure, partial closure, or response. Data were extracted as intention-to-treat analyses and pooled by using a random-effects model. Proportions of patients who received placebo and had complete or partial fistula(e) closure were calculated, with 95% confidence intervals (CIs). The effects of trial characteristics on the magnitude of response to placebo were examined.
RESULTS
Thirteen RCTs were eligible for our analysis; these included 579 patients assigned to placebo groups. The pooled rate of response to placebo, among all RCTs, for complete fistula closure was 15.6% (95% CI, 10.9%-20.9%), with significant heterogeneity (I(2) = 62.5%, P = .001). The pooled rate of response to placebo for partial fistula closure or response in 9 trials, comprising 423 patients, was 18.3% (95% CI, 14.8%-22.1%). Rates of response to placebo were significantly lower in trials with shorter durations of therapy and shorter intervals to assessment of fistula closure. Neither exposure to the pharmacologic agent during the induction phase of the same (or related) RCT nor concomitant medications had any effect.
CONCLUSIONS
In a meta-analysis of rate of response to placebo in patients with fistulizing CD, we found that fistulae closed in almost 1/6 patients given placebo in RCTs of pharmacologic agents. Future research should identify characteristics of patients that predict response to placebo.
Topics: Crohn Disease; Fistula; Humans; Placebo Effect; Placebos; Randomized Controlled Trials as Topic
PubMed: 25218669
DOI: 10.1016/j.cgh.2014.08.038 -
Medecine Sciences : M/S 2019A placebo drug is defined as a treatment without any specific pharmacological efficacy, that works when the patient thinks to receive an active treatment, through a... (Review)
Review
A placebo drug is defined as a treatment without any specific pharmacological efficacy, that works when the patient thinks to receive an active treatment, through a psychological and physiological mechanism. This study aimed to evaluate the use of placebo in French hospitals, in Polyvalent Medicine units. A questionnaire comprising 15 items was sent to 372 units. The analysis of 153 responses was conducted from dynamic crosstabs in Excel and using the R software available online. The survey confirmed that the use of placebos in hospital is frequent, with nearly 2/3 of professionals answering the questionnaire declared to use it. The oral capsule is the most commonly used form. Placebo is mainly administered at night, in case of pain, insomnia or anxiety, to so-called "difficult" patients. Placebo is not always given after medical prescription. In most cases, patients are not informed that they receive a placebo. The majority of professionals believed in the placebo effect but considered to be insufficiently informed and trained in the use of placebo in current practice. Although the placebo effect is now demonstrated, ethical and legal considerations recommend placebo treatment only on medical prescription, with the prior information of the patient. The placebo could be used as complementary therapy to conventional treatment in the cases of this therapeutic effectiveness has been demonstrated. Professionals should be trained in the use of placebo in order to avoid nocebo effect and potentiate beneficial effects of placebo.
Topics: Adult; Disclosure; Female; France; General Practice; Hospital Units; Hospitals; Humans; Male; Morals; Physician-Patient Relations; Placebo Effect; Placebos
PubMed: 31532380
DOI: 10.1051/medsci/2019127 -
PloS One 2014Surveys of doctors suggest that they use placebos and placebo effects clinically to help patients. However, patients' views are not well-understood. We aimed to identify...
BACKGROUND
Surveys of doctors suggest that they use placebos and placebo effects clinically to help patients. However, patients' views are not well-understood. We aimed to identify when and why placebo-prescribing in primary care might be acceptable and unacceptable to patients.
METHODS
A purposive diverse sample of 58 English-speaking adults (18 men; aged 19-80 years) participated in 11 focus groups. Vignettes describing doctors prescribing placebos in primary care were used to initiate discussions. Data were analyzed inductively.
RESULTS
Participants discussed diverse harms and benefits of placebo-prescribing for individual patients, carers, healthcare providers, and society. Two perspectives on placebo-prescribing were identified. First, the "consequentialist" perspective focused on the potential for beneficial outcomes of placebo-prescribing. Here, some participants thought placebos are beneficial and should be used clinically; they often invoked the power of the mind or mind-body interactions. Others saw placebos as ineffective and therefore a waste of time and money. Second, the "respecting autonomy" perspective emphasized the harms caused by the deceptive processes thought necessary for placebo-prescribing. Here, participants judged placebo-prescribing unacceptable because placebo-prescribers deceive patients, thus a doctor who prescribes placebos cannot be trusted and patients' autonomy is compromised. They also saw placebo-responders as gullible, which deterred them from trying placebos themselves. Overall, the word "placebo" was often thought to imply "ineffective"; some participants suggested alternative carefully chosen language that could enable doctors to prescribe placebos without directly lying to patients.
CONCLUSIONS
Negative views of placebos derive from beliefs that placebos do not work and/or that they require deception by the doctor. Positive views are pragmatic in that if placebos work then any associated processes (e.g. mechanisms, deception) are deemed unimportant. Public education about placebos and their effects is warranted and research to identify optimal ways of harnessing placebo effects in clinical practice is needed.
Topics: Adult; Aged; Aged, 80 and over; Female; Focus Groups; Humans; Male; Middle Aged; Patients; Placebo Effect; Placebos; Treatment Outcome; Young Adult
PubMed: 25006673
DOI: 10.1371/journal.pone.0101822 -
The British Journal of Surgery Aug 2020Placebo-controlled trials play an important role in the evaluation of healthcare interventions. However, they can be challenging to design and deliver for invasive...
BACKGROUND
Placebo-controlled trials play an important role in the evaluation of healthcare interventions. However, they can be challenging to design and deliver for invasive interventions, including surgery. In-depth understanding of the component parts of the treatment intervention is needed to ascertain what should, and should not, be delivered as part of the placebo. Assessment of risk to patients and strategies to ensure that the placebo effectively mimics the treatment are also required. To date, no guidance exists for the design of invasive placebo interventions. This study aimed to develop a framework to optimize the design and delivery of invasive placebo interventions in RCTs.
METHODS
A preliminary framework was developed using published literature to: expand the scope of an existing typology, which facilitates the deconstruction of invasive interventions; and identify placebo optimization strategies. The framework was refined after consultation with key stakeholders in surgical trials, consensus methodology and medical ethics.
RESULTS
The resulting DITTO framework consists of five stages: deconstruct treatment intervention into constituent components and co-interventions; identify critical surgical element(s); take out the critical element(s); think risk, feasibility and role of placebo in the trial when considering remaining components; and optimize placebo to ensure effective blinding of patients and trial personnel.
CONCLUSION
DITTO considers invasive placebo composition systematically, accounting for risk, feasibility and placebo optimization. Use of the framework can support the design of high-quality RCTs, which are needed to underpin delivery of healthcare interventions.
Topics: Humans; Placebos; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 32187680
DOI: 10.1002/bjs.11509 -
Arquivos de Gastroenterologia 2020Inflammatory bowel disease comprises two distinct conditions - Crohn's disease and ulcerative colitis - which can be treated with immunomodulators. A non-neglectable... (Review)
Review
Inflammatory bowel disease comprises two distinct conditions - Crohn's disease and ulcerative colitis - which can be treated with immunomodulators. A non-neglectable proportion of these patients will need biologic therapy, and many patients under biologic treatment will experience either primary or secondary failure. As a consequence, clinical trials evaluating new therapeutic alternatives are being developed. These trials share common features, such as being controlled with placebo. Placebo use in clinical trials is a matter of intense debate. Those who support placebo use highlight the methodologic advantages placebo-controlled trials have. Those against placebo use argue that it would be against ethical principles in clinical research to expose a patient to placebo when a valid therapeutic alternative exists. In this review, we summarize the existing arguments for and against the use of placebo in the context of inflammatory bowel disease research. We finally suggest that it is very likely that in the near future inflammatory bowel disease trials will no longer be controlled with a placebo arm, but instead they will be non-inferiority trials with an active comparator.
Topics: Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Humans; Placebos
PubMed: 32294741
DOI: 10.1590/S0004-2803.202000000-15 -
Medicina (Kaunas, Lithuania) Apr 2019Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by gastrointestinal and extraintestinal manifestations triggered after gluten ingestion in the absence... (Review)
Review
Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by gastrointestinal and extraintestinal manifestations triggered after gluten ingestion in the absence of celiac disease and wheat allergy. Because of the lack of biomarkers for NCGS diagnosis, the cornerstone for its assessment is a single- or double-blind placebo-controlled (DBPC) gluten challenge. However, there are some non-standardized points in the diagnostic approach proposed by the experts. This complicate comparisons among the results published by different research groups. The gluten vehicle and placebo must be indistinguishable from each other, which entails sensory and technological evaluations of the designed gluten vehicle and placebo products. At the moment, there is no standardized method for the preparation of the gluten vehicle and placebo for carrying out DBPC gluten challenges for NCGS assessment. This review focuses on the challenges that researchers have to face, either for the development of an accepted gluten vehicle and placebo or for identifying NCGS cases on the basis of DBPC gluten challenges.
Topics: Food Hypersensitivity; Glutens; Humans; Placebos; Wheat Hypersensitivity
PubMed: 31035487
DOI: 10.3390/medicina55050117 -
Homeopathy : the Journal of the Faculty... Nov 2017
Topics: Consensus Development Conferences as Topic; Europe; Homeopathy; Humans; Materia Medica; Placebos; Research Support as Topic; Societies, Medical
PubMed: 29157468
DOI: 10.1016/j.homp.2017.10.001 -
Psychogeriatrics : the Official Journal... Nov 2017Choto-san is a traditional medicine used for hypertension and headaches in Japan and China. Some studies have shown its effectiveness in the treatment of dementia. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Choto-san is a traditional medicine used for hypertension and headaches in Japan and China. Some studies have shown its effectiveness in the treatment of dementia. The present review aimed to assess the effectiveness and acceptability of Choto-san in the treatment of adults with cognitive impairment.
METHODS
We included randomized controlled trials comparing Choto-san with placebo for patients with dementia or mild cognitive impairment.
RESULTS
Three randomized controlled trials evaluating 219 participants were included. Two were studies on vascular dementia, and the other was on Alzheimer's dementia. There was no difference between Choto-san and placebo in terms of short-term dichotomous judgement of improvement, but Choto-san was more effective than placebo in terms of short-term improvement of cognitive function as measured by continuous outcomes. Also, dropouts judged it to be acceptable. However, the results were imprecise and/or heterogeneous. The number of participants included in the analysis was small (n = 199 in the primary analysis) and sometimes inconsistent, as indicated by the large I (72% in the primary analysis).
CONCLUSION
Low-quality evidence was suggestive of Choto-san's efficacy for vascular dementia, but the present results may be overestimated. Studies with a larger sample size and conducted over longer periods should be performed. Regardless, Choto-san can be one of the choices for the treatment of vascular dementia as it is well tolerated.
Topics: Cognition Disorders; Dementia; Drugs, Chinese Herbal; Humans; Placebos; Plant Extracts; Plants, Medicinal; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28589702
DOI: 10.1111/psyg.12275 -
The Journal of Pediatrics Mar 2017To investigate the magnitude and determinants of the placebo response in studies with pediatric abdominal pain-related functional gastrointestinal disorders. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To investigate the magnitude and determinants of the placebo response in studies with pediatric abdominal pain-related functional gastrointestinal disorders.
STUDY DESIGN
The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL were searched for systematic reviews and randomized placebo-controlled trials concerning children 4-18 years of age with an abdominal pain-related functional gastrointestinal disorder. The primary outcome was the pooled proportion of subjects assigned to placebo with improvement as defined by the authors. The effect of trial characteristics on the magnitude of the placebo response was investigated using univariate meta-regression analysis.
RESULTS
Twenty-one trials were identified. The pooled proportion of subjects with improvement was 41% (95% CI, 34%-49%; 17 studies) and with no pain was 17% (95% CI, 8%-32%; 7 studies). The pooled standardized mean difference on the Faces Pain Scales compared with baseline was -0.73 (95% CI, -1.04 to -0.42; 8 studies). There was significant heterogeneity across studies with respect to both outcomes. Lower dosing frequency (P = .04), positive study (P = .03), longer duration of treatment (P < .001), and higher placebo dropout (P < .001) were associated with higher report of no pain. Response on Faces Pain Scales was greater in studies conducted in the Middle East (P = .002), in studies that did not report the randomization schedule (P = .02), and in studies with a higher percentage of females (P = .04).
CONCLUSIONS
Approximately 41% of children with abdominal pain-related functional gastrointestinal disorders improve on placebo. Several trial characteristics are correlated significantly with the proportion of patients with no pain on placebo and with the magnitude of the placebo response on Faces Pain Scales. These data could be valuable for the design of future studies.
Topics: Abdominal Pain; Adolescent; Child; Child, Preschool; Female; Gastrointestinal Diseases; Humans; Male; Pain Measurement; Pediatrics; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Reference Values; Severity of Illness Index; Treatment Outcome
PubMed: 28081889
DOI: 10.1016/j.jpeds.2016.12.022