scholarly journals Placebo control in Covid-19 trials: A missed opportunity for international guidance

2021 ◽  
pp. 01-04
Author(s):  
Urban Wiesing ◽  
Hans-Jörg Ehni
Keyword(s):  
Biomedical Research ◽  
Ethical Dilemmas ◽  
Placebo Control ◽  
Vaccine Research ◽  
Ethical Conflict ◽  
Control Groups ◽  
Global Regulation ◽  
Placebo Controls ◽  
New System ◽  
Missed Opportunity

Vaccines preventing Covid-19 have been approved in several countries. Is it still ethically acceptable to use placebo controls during the development of other vaccine options? If two of the most influential international guidelines of biomedical research are consulted, the Declaration of Helsinki and the CIOMS-guidelines, the answer is “no”. We discuss the implications for ongoing vaccine research, and how placebo controls might be justified nevertheless. However, the ethical conflict remains highly problematic. We suggest that such ethical dilemmas should be avoided in the future by the introduction of a new system of global governance. Once vaccines are approved, a global regulation should oblige producers to provide the necessary amount of vaccine doses for the control groups of ongoing vaccine research.

A trial of sepia 200

1995 ◽  
Vol 84 (01) ◽  
pp. 14-20 ◽  
Author(s):  
A.V. Williamson ◽  
W.J. Crawford ◽  
B. Rennie ◽  
W.L. Mackie
Keyword(s):  
Reproductive Performance ◽  
Disease Risk ◽  
Controlled Trial ◽  
Mean Value ◽  
Post Treatment ◽  
Placebo Control ◽  
Control Groups ◽  
Placebo Controls ◽  
Group Data ◽  
The Difference

AbstractThe effect of Sepia 200c on the reproductive performance of Friesian cross dairy cows was assessed in a controlled trial from September 1989 until August 1990. Overall reproductive performance was monitored monthly and pregnancy diagnosis and cyclical status was determined. The cows were randomly allocated to 4 groups, untreated controls, placebo controls, Sepia-treated 24 to 48 hours postpartum and Sepia-teated day 14 postpartum.The trial was concluded in July 1990 when another treatment was employed to reduce declining herd reproductive status. Statistical analysis of the results was based on differences between the placebo control and the Sepia-treated, 24–48 hours postpartum, the pooled control groups and placebo control with Sepia day 14, and lastly the difference between the 2 Sepia-treated groups.The highest rates of periparturient disease occurred in the Sepia-treated groups, the highest single incidence rate of periparturient disease risk (cysts) found in the cows in the Sepia 24 to 48 hours postpartum group. Sepia day 14 produced the largest percentage of cows seen in first oestrus (45%), the largest number of observed heats (60%) in the cows without periparturient disease risk factors or recurrent traits and the lowest total mean value days to oestrus post-treatment.Sepia day 14 produced the largest percentage that held to first service, the lowest post-treatment period to first service, calving to conception interval, mean number of services and rectal examinations per conception, mean day calving interval and calving index. The results show that the effect of Sepia 200c administered to cows two weeks postpartum increased the numbers of cows observed in first oestrus, held to first service and lowered the calving to conception interval and calving index. The results of the Sepia day 14 postpartum group were also found to be compatible with the same group data reported in the previous study.

scholarly journals Study the effect of supplement Stop-Cystitis® Plus in diseases of the urinary tract of cats and dogs

2021 ◽  
Vol 2021 (1) ◽  
pp. 32-37
Author(s):  
Ol'ga Petrova
Keyword(s):  
Amino Acids ◽  
Urinary Tract ◽  
Clinical Examination ◽  
Placebo Control ◽  
Biochemical Profile ◽  
Control Groups ◽  
Chemical Indicators ◽  
Treatment Complications ◽  
Baseline Values ◽  
Physical And Chemical

In this article were present of effectiveness Stop-cystitis® Plus drug containing the amino acids tryptophan, methionine and L-theonine and herbal. Evaluation of efficiency was carried out on the basis of a comprehensive clinical examination, analysis of physical and chemical indicators of urine, blood values (clinical and biochemical profile), ultrasound, cystocentase and microscopy, etc. Relapses after treatment, complications were monitored, and the dynamics of restoring the physiology of urination in animals was determined. For comparison, we used the indicators for placebo control groups and baseline values in healthy animals.

scholarly journals Placebo comparator group selection and use in surgical trials: the ASPIRE project including expert workshop

2021 ◽  
Vol 25 (53) ◽  
pp. 1-52
Author(s):  
David J Beard ◽  
Marion K Campbell ◽  
Jane M Blazeby ◽  
Andrew J Carr ◽  
Charles Weijer ◽  
...  
Keyword(s):  
Randomised Controlled Trials ◽  
Medical Research Council ◽  
Placebo Control ◽  
Controlled Trials ◽  
Surgical Trials ◽  
Surgical Interventions ◽  
Placebo Controls ◽  
Randomised Controlled ◽  
The Uk ◽  
Future Work

Background The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. Design To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. Setting A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. Results To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. Conclusions The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Limitations Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. Funding Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council–National Institute for Health Research Methodology Research programme.

Can Reliance be Placed on a Single Meta-Analysis?

1990 ◽  
Vol 24 (3) ◽  
pp. 405-415 ◽  
Author(s):  
Nathaniel McConaghy
Keyword(s):  
Literature Review ◽  
Effect Size ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Effect Sizes ◽  
Control Groups ◽  
Consistent Finding ◽  
Placebo Controls ◽  
Effect Of Treatment ◽  
Meta Analyses

Meta-analysis replaced statistical significance with effect size in the hope of resolving controversy concerning evaluation of treatment effects. Statistical significance measured reliability of the effect of treatment, not its efficacy. It was strongly influenced by the number of subjects investigated. Effect size as assessed originally, eliminated this influence but by standardizing the size of the treatment effect could distort it. Meta-analyses which combine the results of studies which employ different subject types, outcome measures, treatment aims, no-treatment rather than placebo controls or therapists with varying experience can be misleading. To ensure discussion of these variables meta-analyses should be used as an aid rather than a substitute for literature review. While meta-analyses produce contradictory findings, it seems unwise to rely on the conclusions of an individual analysis. Their consistent finding that placebo treatments obtain markedly higher effect sizes than no treatment hopefully will render the use of untreated control groups obsolete.

Ethics of Death and Dying: Historical Perspective

1979 ◽  
Vol 9 (3) ◽  
pp. 203-237 ◽  
Author(s):  
Gerald J. Gruman
Keyword(s):  
Intellectual History ◽  
Biomedical Research ◽  
Medical Practice ◽  
Historical Perspective ◽  
Ethical Dilemmas ◽  
Death And Dying ◽  
Therapeutic Principle ◽  
The Individual

The ethical dilemmas surrounding dying and death today can be understood more adequately when placed in an historical perspective. The methodology of intellectual history is employed to examine the sequence of cultural stages from prehistory to the contemporary scene, using the concept of the death system (Kastenbaum) as an organizing formulation. It is suggested in conclusion that a modern version of the meliorist ethos can lend support to the on-going modes of biomedical research and the application of the activist therapeutic principle in medical practice. Humanity has labored and suffered too much to abandon hope at this time and either submerge the personality of the individual or turn to a nihilistic “death worship” (Borkenau).

Effects of Visuo-motor Behavior Rehearsal, Relaxation, and Imagery on Karate Performance

1981 ◽  
Vol 3 (3) ◽  
pp. 228-238 ◽  
Author(s):  
Robert S. Weinberg ◽  
Thomas G. Seabourne ◽  
Allen Jackson
Keyword(s):  
Trait Anxiety ◽  
State Anxiety ◽  
Motor Behavior ◽  
Test Period ◽  
Attention Control ◽  
Placebo Control ◽  
Performance Tests ◽  
Control Groups ◽  
Testing Period ◽  
Anxiety Trait

The present investigation attempted to determine whether imagery combined with relaxation (VMBR) is more effective in facilitating karate performance than either imagery or relaxation alone. Each subject (N = 32) was randomly assigned to either a VMBR, relaxation, imagery, or attention-placebo control condition in a one-way design. During the first day of the karate class (which met twice a week), each group was individually provided with an explanation of how to practice their assigned strategy at home. Trait anxiety tests were administered at the beginning and the end of the 6-week test period. In addition, performance tests were administered at the end of the testing period along with precompetitive state anxiety. Trait anxiety results indicated that all subjects displayed a reduction in trait anxiety over the course of the testing period. State anxiety results indicated that the VMBR and relaxation groups exhibited lower levels of state anxiety than the imagery and attention-control groups. Performance was broken down into three subareas which consisted of skill, combinations, and sparring (actual competition). Results only showed an effect for sparring, with VMBR group exhibiting better performance than all other groups.

scholarly journals Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients.

2020 ◽  
Author(s):  
Flavio A. Cadegiani ◽  
Andy Goren ◽  
Carlos G. Wambier ◽  
John McCoy
Keyword(s):  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Control Group ◽  
Placebo Control ◽  
Control Groups ◽  
Persistent Symptoms ◽  
Number Of Patients ◽  
Outpatient Settings

Abstract Background: While there was a lack of pharmacological interventions proven to be effective in early, outpatient settings for COVID-19, in a prospective, open-label observational study (pre-AndroCoV Trial) the use of nitazoxanide, ivermectin and hydroxychloroquine demonstrated similar effects, and apparent improvement of outcomes compared to untreated patients. The unexpected apparent positive results led to ethical questions on the employment of further full placebo-control studies in early stage COVID-19. The objective of the present study was to elucidate whether the conduction of a full placebo-control RCT was still ethically viable, through a comparative analysis with two control-groups.Materials and methods: Active group (AG) consisted of mild-to-moderate early stage COVID-19 patients enrolled in the Pre AndroCoV-Trial, treated with nitazoxanide ivermectin, or hydroxychloroquine in selected cases, in association with azithromycin. Vitamin D, vitamin C, zinc, glucocorticoids and anticoagulants, when clinically recommended. Control Group 1 (CG1) consisted of a retrospectively obtained group of untreated patients from the same population as those from the Pre-AndroCoV Trial, and Control Group 2 (CG2) resulted from a precise prediction of clinical outcomes, based on a thorough and structured review of articles indexed in PubMed and MEDLINE and statements by official government agencies and specific medical societies. For both CGs, patients were matched for proportion between sex, age, obesity and other comorbidities. Results: Compared to CG1 and CG2, AG showed a reduction of 31.5 to 36.5% in viral shedding (p < 0.0001), 70 to 85% and 70 to 73% in duration of COVID-19 clinical symptoms when including and not including anosmia and ageusia, respectively ((p < 0.0001 for both), and 100% in respiratory complications through the parameters of the Brescia COVID-19 Respiratory Scale (p < 0.0001). For every 1,000 confirmed cases for COVID-19, a minimum of 140 patients were prevented from hospitalization (p < 0.0001), 50 from mechanical ventilation, and five deaths, when comparing to age-, sex- and comorbidity-matched non-treated patients with similar initial disease severity at the moment of diagnosis.Conclusion: Apparent benefits of the combination between early detection and early pharmacological approaches for COVID-19 demonstrated to be consistent when when compared to different control groups of untreated patients. The potential benefits could allow a large number of patients prevented from hospitalizations, deaths and persistent symptoms after COVID-19 remission. The potential impact on COVID-19 disease course and numbers of negative outcomes and the well-established safety profile of the drugs proposed by the Pre-AndroCoV Trial led to ethical questions regarding the conduction of further placebo control randomized clinical trials (RCTs) for early COVID-19. Early pharmacological approaches including azithromycin in combination with any of the options between nitazoxanide, ivermectin or optionally hydroxychloroquine should be considered for those diagnosed with COVID-19 presenting less than seven days of symptoms. Of the three drugs, we opted for nitazoxanide, due to more extensive demonstration of in vitro and in vivoantiviral activity, proven efficacy against other viruses in humans, and steadier safety profile.

Evidence for the Efficacy of an Opioid-Sparing Effect of Intravenous Acetaminophen in the Surgery Patient: A Systematic Review

Pain Medicine ◽  
2020 ◽  
Vol 21 (12) ◽  
pp. 3301-3313
Author(s):  
Daniel E Hilleman ◽  
Mark A Malesker ◽  
Sarah J Aurit ◽  
Lee Morrow
Keyword(s):  
Systematic Review ◽  
Active Control ◽  
Opioid Consumption ◽  
Placebo Control ◽  
Control Groups ◽  
Systematic Analysis ◽  
Active Comparator ◽  
Opioid Sparing ◽  
Analgesic Agents ◽  
Sparing Effect

Abstract Background Intravenous (IV) acetaminophen is used in multimodal analgesia to reduce the amount and duration of opioid use in the postoperative setting. Methods A systematic review of published randomized controlled trials was conducted to define the opioid-sparing effect of IV acetaminophen in different types of surgeries. Eligible studies included prospective, randomized, double-blind trials of IV acetaminophen compared with either a placebo- or active-treatment group in adult (age ≥18 years) patients undergoing surgery. Trials had to be published in English in a peer-reviewed journal. Results A total of 44 treatment cohorts included in 37 studies were included in the systematic analysis. Compared with active- or placebo-control treatments, IV acetaminophen produced a statistically significant opioid-sparing effect in 14 of 44 cohorts (32%). An opioid-sparing effect was more common in placebo-controlled comparisons. Of the 28 placebo treatment comparisons, IV acetaminophen produced an opioid-sparing effect in 13 (46%). IV acetaminophen produced an opioid-sparing effect in only 6% (one out of 16) of the active-control groups. Among the 16 active-control groups, opioid consumption was significantly greater with IV acetaminophen than the active comparator in seven cohorts and not significantly different than the active comparator in eight cohorts. Conclusions The results of this systematic analysis demonstrate that IV acetaminophen is not effective in reducing opioid consumption compared with other adjuvant analgesic agents in the postoperative patient. In patients where other adjuvant analgesic agents are contraindicated, IV acetaminophen may be an option.

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