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The impact of treatment and other clinical and community health interventions: A ‘does it work?’ evaluation
Published in Milos Jenicek, Foundations of Evidence-Based Medicine, 2019
The clinical trial closest to the experiment is the ‘randomized, double-blind, placebo-controlled’ trial. Its title reflects three fundamental precautions (added to observational design) to ensure maximum objectivity of findings and their interpretation. Randomization is the procedure of assigning subjects to treatment groups using the effect of chance. Blinding is the procedure that makes the nature of the observations and actions unknown to the participants (patients) and the investigators. Unbiased reading and interpretation of findings is sought this way. Placebo represents an inactive, ‘sham’ treatment (drug, surgical procedure, etc.) to which the active procedure under study is compared. Starch pills, saline solution injections or skin-deep incisions instead of full operations may serve as placebos. It is, however, sometimes desirable that the placebo imitate the side effects of the active procedure (for example, extrapyramidal effects of psychoactive drugs, etc.), thus being called an ‘active placebo’. The placebo procedure is selected at the moment of trial planning as soon as control groups are considered. Randomization is performed at stage 4. Blinding applies to the whole trial except for its planning and interpretation after the statistical analysis of findings.
Very few patients benefit from the drugs they take
Published in Peter C. Gøtzsche, Richard Smith, Drummond Rennie, Deadly Medicines and Organised Crime, 2019
Peter C. Gøtzsche, Richard Smith, Drummond Rennie
For many drugs, it’s relatively easy to overcome the fundamental problem with breaking of the blind through side effects by using so called ‘active placebos’. The term is somewhat misleading, as the idea is not that the placebo should contain a substance that is active against the disease, only a substance that gives a similar side effect as the active drug. For antidepressants, trials have been performed where the placebo contained atropine, which causes dryness in the mouth like the active drugs. As expected, such trials showed a considerably smaller difference between drug and placebo than trials that didn’t use an ‘active placebo’.14
Opioid Therapy for Chronic Noncancer Pain: Cautions, Concerns, Misconceptions, and Potential Myths
Published in Mark V. Boswell, B. Eliot Cole, Weiner's Pain Management, 2005
Michael E. Clark, Robert W. Young, B. Eliot Cole
One potential solution to this problem of ineffective blinding involves the use of an active placebo as the opioid comparison group. An active placebo is a pharmaceutical selected based on similarities between its adverse effects profile and that of the opioid under study. If ineffective blinding due to the use of inactive placebos occurs, one would expect to find increased pain reduction when appropriate active placebos are employed. In the CNCP OT literature we could identify only two studies that used an active placebo (benztropine). In the first study (Moulin et al., 1996), the authors found that following the opioid to placebo crossover, the pain intensity scores of active placebo subjects actually were lower than those of opioid subjects (see Figure 11.1, weeks 15 through 20), suggesting that either their crossover procedures failed or that morphine was no more effective than the active placebo in reducing pain. The fact that Moulin and colleagues also systematically assessed the integrity of their blinding procedures and reported that 47.8% of subjects and 67.4% of investigators correctly identified treatment with morphine suggested that the blind was only partially successful. In the second study (Watson et al., 2003), which examined opioid efficacy with neuropathic pain, the active placebo subjects experienced substantially less pain reduction than the opioid group. However, when they assessed the integrity of their blinding procedure, they found that 88% of their subjects and investigators correctly identified the opioid condition. Thus, in this case the blind clearly was not maintained despite the use of a placebo with an adverse effects profile similar to the opioid analgesic, and the advantage of opioid over placebo that they reported may have reflected subject and experimenter bias. They also commented on the special difficulties maintaining study blinds in crossover trials, even when active placebos are used, due to subject and experimenter exposure to both conditions.
Cognitive remediation therapy for post-acute persistent cognitive deficits in COVID-19 survivors: A proof-of-concept study
Published in Neuropsychological Rehabilitation, 2023
Mariagrazia Palladini, Beatrice Bravi, Federica Colombo, Elisa Caselani, Camilla Di Pasquasio, Greta D’Orsi, Patrizia Rovere-Querini, Sara Poletti, Francesco Benedetti, Mario Gennaro Mazza
Nevertheless, these results must be viewed in light of some weaknesses. First, the limited sample size of the present investigation prevents us from generalizing the favourable effect of CRT. Second, both the neuropsychological assessment and the training sessions were conducted by the same psychologist, possibly inducing subjective influence in the post-treatment testing. As our work only involves a passive control group, further studies should include an active placebo condition in order to control for non-specific therapist/patient-related effects, such as demand characteristics, attention or care. Notwithstanding the successful application of a matching routine afterward, the lack of a structured double-blind randomization design makes it challenging to disentangle the beneficial effect of CRT from the bias related to the ability/inability to regularly attend the full programme. However, our procedure allowed us to meet a clinical need and preserve a more naturalistic setting.
Irving Kirsch opens a window on antidepressant medications
Published in American Journal of Clinical Hypnosis, 2023
Emma Grace Chen, Alison Kate Oliver, Amir Raz
Rather than prescribing standard sugar pill placebos, one might consider swapping the roles and prescribing antidepressants as active, rather than inert, placebos. An active placebo is a drug that should not have any major effect on the condition being treated, but it may produce side effects – the ones for which antidepressants are so famous. Frequently, patients believe these placebos are actually active drugs because they can feel the adverse effects. However, the side effects of antidepressants make for an extensive and unpleasant list. The most common side effect is sexual dysfunction; 75% of patients on SSRIs end up developing some form of sexual impairment (Modell, Katholi, Modell, & DePalma, 1997). Moreover, this sexual dysfunction can linger even after the treatment has ended – post-SSRI sexual dysfunction (PSSD). Antidepressants also come with an increased likelihood of long-term weight gain, insomnia, diarrhea, and nausea.
Blinding and expectancy confounds in psychedelic randomized controlled trials
Published in Expert Review of Clinical Pharmacology, 2021
Suresh D. Muthukumaraswamy, Anna Forsyth, Thomas Lumley
A standard parallel groups design with an active comparator (Figure 2e) may still be appropriate provided that the active comparator has convincing enough psychedelic properties that a reasonable patient given placebo would believe they had been allocated to the treatment. For example, take a trial where ketamine is the treatment and midazolam the active placebo. Pre-testing may indicate that all participants in the ketamine group might correctly guess their treatment arm, while half of those given midazolam may believe they had been administered ketamine. In the RCT, participants could be allocated in a 1:2 ratio favoring placebo, although it is not necessary to state the allocation ratio to participants; indeed, there may be advantages to mild deception for this factor. As per Section Assessment of Masking Success in Clinical Trials, soon after the intervention, but prior to outcome assessment, belief about the allocation intervention can be measured (B). Only those participants in the control group who believe they are in the active group Equation 14). As noted above, sophisticated approaches are possible where there is a greater uncertainty in B as long as the uncertainty is not informative about actual treatment. One potential issue with this design is because the stratification on B is performed post-randomization, one can no longer assume that pre-trial covariates are balanced.