Legitimacy in the absence of double-blind randomised clinical trials


double-blind randomised

Double-blind randomised clinical trials

A double-blind randomised clinical trial prevents bias when evaluating patient outcomes, validating the research. It is referred to as a double-blind study, as neither the researcher nor the patient knows who has received an intervention and who has received a placebo.

However, it is almost impossible to conduct double-blind studies in psychotherapy, and consequently psychedelic-assisted therapy, due to the patient’s active involvement in the therapy component. 

As a result, studies can only be single blind, with therapists unaware of the treatment patients have received. This can weaken the legitimacy of the research, as it presents the opportunity for conscious and unconscious bias to occur, with drug developers able to overstate treatment efficacy to raise capital and share prices. 

This can create a conundrum for drug developers, who need to undertake rigorous research to attract investment but cannot conduct double-blind trials. To produce scientifically valid research, psychedelic drug developers instead need to design clinical trials that draw upon best practices from blinded randomised studies. 

Randomised clinical trials

Randomised clinical trials involve at least two different study groups, one of which receives a placebo or conventional treatment that the psychedelic medicine is benchmarked against. This is called the control group, and study participants are randomly inducted into either the control group or the group receiving the experimental treatment.

Unconscious bias, as the name suggests, is unintentional but can still influence clinical trials and the conclusions drawn. For instance, researchers may unwittingly place those with less severe symptoms into the experimental group, but these patients may respond better due to their lower condition severity.

For this reason, the age, gender and symptom severity of participants may be taken into account prior to group allocation. Although this may detract from the arbitrary nature of the trial, it does enable researchers to better compare groups without accounting for differences in study participants.

Blinded clinical trials

By ensuring researchers and study participants are blinded as to whether an intervention or placebo was administered, it prevents the former from treating study groups differently. This is essential to mitigate confirmation bias in investigators and avoid an excessive placebo effect in participants, which may distort the results of the study. 

Without blinding clinical trials, there is an increased risk of false positives occurring and treatment efficacy being overstated. This bias could present itself in the collection of data, the analysis of the data or even in its presentation – resulting in inaccurate conclusions being drawn.

Considerations for psychedelic healthcare

Double-blind randomised clinical trials are essential to legitimise research, particularly when the intervention has been stigmatised following decades of prohibition.

However, psychiatric conditions, such as major depressive disorder and generalised anxiety disorder, are typically measured on subjective rating scales and treated through cognitive behavioural therapy – with patient scores on these scales treated as study endpoints.

In spite of this, it is crucial that interventions with subjective endpoints are investigated with the same rigour as double-blinded studies. This ensures that the potential benefits of psychiatric drugs, including psychedelic medicines, are not overstated and that the research holds weight in scientific circles.

Although the MHRA and FDA do not require researchers to conduct double-blind controlled studies, they are seen as the gold standard of clinical trials and help drug developers attract investment. In the absence of double-blind studies in psychedelic healthcare, rigorously designed clinical trials are essential.

Designing rigorous clinical trials

A study led by Imperial College London involved ‘self-blinding’, whereby participants mixed doses of psychedelic medicines with a placebo. Over a four-week period, some taking psychedelic medicines, and others a placebo, they filled out surveys on their experiences and completed online cognitive tests.

Both groups reported similar psychological benefits, with the conclusion drawn that improvements were likely the result of personal expectation, the placebo effect, rather than an undetected mechanism of action. 

David Erritzoe, a Clinical Senior Lecturer at Imperial College London, said, ‘The successful execution of this study could inspire similar studies in a broad range of scientific or medical contexts.

‘Accounting for the placebo effect is important when assessing trends… where social pressure or users’ expectations can lead to a strong placebo response. Self-blinding citizen science initiatives could be used as an inexpensive initial screening tool before launching expensive clinical studies.’

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