Nebulized Salbutamol for Treatment of Transient Tachypnea of the Newborn: A Randomized Placebo-controlled Clinical Trial in Iran

Should the Food and Drug Administration Limit Placebo-Controlled Trials?

In this issue, Temple and Ellenberg address the ethical challenge presented by use of placebo controls. Under what circumstances are placebo controls ethical, and what alternatives are available?

Centrally active nonhormonal hot flash therapies

A Meta-Analysis of the Placebo Rates of Remission and Response in Clinical Trials of Active Ulcerative Colitis

Critical Missing Data on Erythropoiesis-Stimulating Agents in CKD: First Beat Placebo

Chapter 44 - Withdrawal studies: Design, measures, and classic examples

Implantation of CD133+ Stem Cells in Patients Undergoing Coronary Bypass Surgery

BackgroundThe value of neuraminidase inhibitors (NAIs) in reducing severe clinical outcomes from influenza is debated. A clinical trial to generate better evidence is desirable. However, it is unknown whether UK clinicians would support a placebo-controlled trial. A survey was conducted to determine the attitude of clinicians towards a clinical trial and their current practice in managing adults admitted to hospital with suspected influenza.MethodsSenior clinicians (n = 50) across the UK actively involved in the care of patients hospitalised with severe respiratory infections and/or respiratory infection research were invited to participate in an on-line survey. Participants were asked their opinion on the evidence for benefit of NAIs in influenza, their current practice in relation to: a) testing for influenza; b) treating empirically with NAIs; and c) when influenza infection is virolologically confirmed, prescribing NAIs.ResultsThirty-five (70%) of 50 clinicians completed the survey. Respondents were drawn mainly from infectious diseases, intensive care and respiratory medicine. Only 11 (31%) of 35 respondents agreed that NAIs are effective at reducing influenza mortality; 14 (40%) disagreed, 10 (28.6%) neither agreed nor disagreed. When managing adults admitted to non-ICU wards with a respiratory infection during an influenza season, 15 (51.7%) clinicians indicated they would usually perform a test for influenza in greater than 60% of patients but only 9 (31%) would treat empirically with NAIs in greater than 60% of patients. Few clinicians would either test or empirically treat patients presenting with other (non-respiratory infection related) diagnoses. If influenza infection is confirmed, 17 (64.5%) clinicians would prescribe NAIs in greater than 80% of patients with a respiratory infection treated on non-ICU wards Thirty-one (89%) clinicians agreed that a placebo-controlled clinical trial should be conducted and 29 (85%) would participate in such a trial.ConclusionsThere is strong support from UK clinicians for a placebo-controlled trial of NAI treatment in adults hospitalised with suspected influenza. Current variation in medical opinion and clinical practice demonstrates collective equipoise, supporting ethical justification for a trial. Low use of NAIs in the UK suggests randomisation of treatment would not substantially divert patients towards placebo.

Background<br/><br/>There are ethical shortcomings to current standard practices regarding the provision of information about placebos in clinical trials. Written information about placebos for clinical trial participants can be incomplete and even misleading. We aimed to develop accurate yet accessible written information about placebos for patients who might participate in clinical trials, and to test the effects of such information on patients’ beliefs about placebos.<br/><br/>Methods<br/><br/>With input from 22 patients and public volunteers, a new, “elaborated” information leaflet was developed to provide accessible and evidence-based information about placebos and their possible effects. A “standard” leaflet was also produced which gave a neutral but incomplete description of placebos. In an online experiment 328 participants with chronic health conditions were randomised to read either the elaborated or the standard leaflet. Participants completed validated measures of the credibility and expected effectiveness of placebo treatment for pain and intentions, attitudes, perceived behavioural control, and subjective norms towards taking part in a placebo-controlled trial. <br/><br/>Results<br/><br/>The elaborated leaflet had a significant positive effect on participants’ ratings of the credibility (t(326)=-2.78, p&lt;.01) and effectiveness (t(326)=-2.59, p&lt;.05) of placebo treatment for pain. It had no effect on intentions to take part in placebo-controlled clinical trials. <br/><br/>Conclusions<br/><br/>The elaborated leaflet provided more comprehensive information about placebos than is commonly provided in current clinical trials. Such a leaflet appears to have greater ethical validity and might increase the magnitude of placebo effects. Further research is needed with participants who are actively considering enrolling in a placebo-controlled trial.

Psychosis, Agitation, and Antipsychotic Treatment in Dementia

CVS to phase out tobacco sales, launch smoking cessation program

Lessons from the glitazones

Background: Placebo-controlled trials can provide evidence to inform end-of-life care, but it is contested whether asking dying patients to participate in such trials is morally justifiable. To investigate the experiences of these patients is even more complex. Therefore, proxy assessments by relatives can be a good alternative. Aim: To explore the experience of participating in a placebo-controlled trial at the end of life from the perspective of bereaved relatives. Design: Mixed-method study, including questionnaires and interviews. Setting/participants: The SILENCE study was a randomized, double-blind, placebo-controlled trial on the efficacy of scopolamine butylbromide to prevent death rattle. The study was performed in six inpatient hospice facilities. Patients were asked to participate at admission in the hospice. Three months after the death of the patient, bereaved relatives were invited to fill in a questionnaire and to participate in an interview. One hundred four questionnaires were completed and 17 relatives were interviewed. Results: Fourteen percent of the relatives participating in the questionnaire study considered the participation of their loved one in research a bit burdensome and 10% considered it a bit stressful. Seventeen percent thought that it was a bit burdensome for the patient. Eighty-three percent considered participation in this type of research (very) valuable. The in-depth interviews showed that patients and relatives jointly decided about participation in this double-blind placebo-controlled medication trial. Relatives generally respected and felt proud about patients’ decision to participate. Conclusion: The large majority of bereaved relatives experienced the participation of their dying love one in this RCT as acceptable and valuable.

A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis

The objective of this chapter is to provide an overview of the problems and solutions of randomized placebo-controlled trials in acupuncture. Studies examining how acupuncture might work cover a broad range of physiological systems, ranging from a single biochemical pathway to the whole biological system. Needling, touch, and pressure occur before skin penetration and then surface receptors/structures are stimulated by both shallow and deeper insertions with additional receptors are further stimulated by deeper insertions. This process raises important questions about the use of penetrating and non-penetrating sham acupuncture techniques and placebo effects. In clinical research the placebo treatment must be inert, and only when the provided randomization and blinding are properly used, a trial comparing the test treatment to the placebo treatment can be said as placebo-controlled. A placebo-controlled trial is an explanatory trial since it tests the known mechanisms associated with the treatment. But in hands-on therapies like acupuncture what can constitute a valid placebo control treatment? Are there predictable mechanisms by which acupuncture works suggesting which valid placebo can be used? Are there any sham acupuncture interventions that can constitute placebo treatments? Are they credible to be sham treatments? If they are not inert or credible, then how can we perform placebo-controlled trials on acupuncture? Are such trials possible? Many forms of sham acupuncture have been tried out in efforts to control placebo effects. In the ‘real’ or ‘test’ acupuncture the ‘real’ technique is applied to the ‘real’ acupoints. Thus, sham acupuncture involves varying the techniques of treatment and the locations of treatment. Given these two variables, three basic variations of sham acupuncture are possible. One of these could possibly act as a placebo control research model, provided that the sham techniques are clinically inert and the sites of their application are clinically inert. The other two models act to compare either treatment sites or treatment techniques. In the latter two models placebo can be held equal between treatment groups, but these models are not capable of acting as placebo-controlled trials. The second and third sham models are often used inadvertently as though they were capable of answering the same question as the first or were placebo-controlled clinical trials like the first. This chapter will give an overview on the current status and problems of placebo-controlled trials in acupuncture trials and suggest possible solutions. We can summarize the evidence: so far no sham acupuncture techniques are inert; they are also clinically effective; and no placebo-controlled trials of acupuncture have ever been performed. Given the evidence, we propose to stop performing sham acupuncture studies since they cannot achieve control for placebo effects. We propose a two-pronged approach to address the issues of mechanisms of action and effectiveness.