scholarly journals Placebo controls in clinical trials: concerns about use in relapse prevention studies in schizophrenia

BMJ ◽  
2016 ◽  
pp. i4728 ◽  
Author(s):  
Robin Emsley ◽  
W Wolfgang Fleischhacker ◽  
Silvana Galderisi ◽  
Lisa J Halpern ◽  
Joseph P McEvoy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Relapse Prevention ◽  
Placebo Controls ◽  
Prevention Studies

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
Relapse Prevention ◽  
Remission Induction ◽  
Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

Diarrhea in Placebo Arms of Cancer Studies

2021 ◽  
Vol 1 (5) ◽  
pp. 379-385
Author(s):  
BIRTE J. WOLFF ◽  
JOHANNES E. WOLFF
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Adverse Events ◽  
Healthy Volunteers ◽  
Cancer Prevention ◽  
Cancer Patients ◽  
Systematic Literature Review ◽  
Oncology Clinical Trials ◽  
Prevention Studies ◽  
Cancer Studies

Background/Aim: Diarrhea is among the most common adverse events in early oncology clinical trials, and drug causality may be difficult to determine. Materials and Methods: This is a systematic literature review of placebo arms of randomized cancer trials. Results: Anemia was reported in 95 of 127 placebo monotherapy cohorts. Publications involving healthy volunteers and cancer prevention studies reported lower frequencies than those with cancer patients. The average reported frequency of diarrhea grade 1 or higher among studies in cancer patients was 15%. The maximal reported frequencies for grades 1, 2, 3, 4, 5 were 56, 24, 6, 2, and 0%, respectively. Conclusion: When higher diarrhea frequencies than those are observed in treatment arms of clinical trials, then drug causality is likely.

Evidence-based complementary medicine for palliative cancer care: does it make sense?

2003 ◽  
Vol 17 (8) ◽  
pp. 704-707
Author(s):  
E Ernst ◽  
J Filshie ◽  
Janet Hardy
Keyword(s):  
Clinical Trials ◽  
Complementary Medicine ◽  
Cancer Care ◽  
Randomized Clinical Trials ◽  
Ethical Problems ◽  
Placebo Controls ◽  
Considerable Debate ◽  
Final Verdict ◽  
Conducting Research ◽  
Methodological Difficulties

Complementary medicine is fast becoming an integral part of palliative cancer care. There is considerable debate as to whether such treatments require proof of effectiveness through randomized clinical trials or whether it may suffice that patients adopt them with apparent appreciation. We attempt to raise some of the arguments on both sides. The arguments include the logistical problems of conducting research in palliative care, ethical problems of placebo controls, methodological difficulties of standardizing treatments or quantifying subtle effects and the, often considerable, costs of clinical trials. We feel that neither those who argue against nor those who argue in favour of rigorous clinical trials are entirely wrong or entirely right. However, our final verdict is that an absence of rigorous science will critically hinder progress. This, in turn, would be to the detriment of future patients. Through discussing the strengths and weaknesses of both sets of arguments, both sides might learn valuable lessons.

Ethical, Scientific, and Regulatory Perspectives Regarding the Use of Placebos in Cancer Clinical Trials

2008 ◽  
Vol 26 (8) ◽  
pp. 1371-1378 ◽  
Author(s):  
Christopher K. Daugherty ◽  
Mark J. Ratain ◽  
Ezekiel J. Emanuel ◽  
Ann T. Farrell ◽  
Richard L. Schilsky
Keyword(s):  
Clinical Trials ◽  
Placebo Response ◽  
Drug Approval ◽  
Active Treatment Group ◽  
Cancer Clinical Trials ◽  
Full Disclosure ◽  
Placebo Controls ◽  
Regulatory Standards ◽  
New Treatment ◽  
Oncology Drug Development

PurposeTo examine the ethical, scientific, and regulatory issues in the design and conduct of placebo-controlled cancer clinical trials.MethodsSeveral content experts contributed to this article.ResultsSpecific criteria can be applied to determine the appropriate use of placebos in oncology drug development. Placebo controls may be justified to prove efficacy of a new treatment in diseases with high placebo response rates; in conditions that wax and wane in severity, have spontaneous remissions, or have an uncertain and unpredictable course; when existing therapies are minimally effective or have serious adverse effects; or in the absence of effective therapy. Use of placebos may also be justified to assure blinding of physicians and patients regarding treatment assignment so as to minimize bias in assessment of study end points. If a trial meets these methodologic criteria, it must then fulfill additional criteria to be considered ethical. These criteria include full disclosure to patients and an assurance that participants randomly assigned to placebo are not substantially more likely than those in active treatment group(s) to die; suffer irreversible morbidity, disability, or other substantial harms; suffer reversible but serious harm; or suffer severe discomfort.ConclusionWe conclude that placebo-controlled oncology trials are scientifically feasible, ethically justifiable, and may be necessary or desirable to meet regulatory standards for drug approval. Using cross-over or randomized withdrawal trial designs, requiring inclusion of state-of-the-art palliative care, and developing valid and acceptable surrogates for survival are critical strategies to address some of the ethical dilemmas associated with placebo-controlled trials.

Placebos in Clinical Trials of Psychotropic Medication

1997 ◽  
Vol 42 (3) ◽  
pp. 1-6 ◽  
Author(s):  
Donald Addington ◽  
Richard Williams ◽  
Yvon Lapierre ◽  
Nady El-Guebaly
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
High Risk ◽  
Psychotropic Medication ◽  
Psychotropic Drugs ◽  
Placebo Response ◽  
Response Rates ◽  
Psychotropic Medications ◽  
Placebo Controls

This paper represents the position of the Canadian Psychiatric Association on the ethical and scientific issues related to the use of placebos in the evaluation of new psychotropic drugs. The position taken by the Association is that new psychotropic medications must be shown to be effective and must be weighed against the best current interventions. Placebo controls may be appropriate under certain circumstances, even when an established intervention is effective. These include situations in which placebo response rates are high, variable, or close to response rates for effective therapies. Placebo controls arc also appropriate when established interventions cany a high risk of side effects or are effective against only certain symptoms of the disorder.

scholarly journals Ceteris Paribus: An Epistemological Error with Ethical Consequences

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Chris Arsenault
Keyword(s):  
Clinical Trials ◽  
Standard Of Care ◽  
Ceteris Paribus ◽  
Novel Treatments ◽  
Placebo Controls

Herein I call into question a common epistemological justification for placebo controls, and thereby problematize the use of placebo in many modern clinical trials. I demonstrate both the ethical harm and epistemic inferiority of placebo controls in certain knowledge contexts, arguing the standard of care should be the more acceptable comparator for novel treatments in such contexts.

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