I find the placebo effect utterly fascinating, Ben Goldacre in an article once referred to the placebo effect as the “coolest strangest thing in medicine”. The fact that inert drugs or treatments can have dramatic effects on the pain a patient is suffering from or stop them feeling nauseated is amazing, I could wax lyrical in this post about how amazing the placebo effect is but I will resist. If you haven’t then read Goldacre’s book – he is far more eloquent on the subject than I could be.
Clinical-trials have to be designed with the placebo effect in mind and ideally the effect of a treatment should be compared to that of a placebo. But is the placebo effect observed in a clinical trial purely subjective or is it actually objective as well? Can the placebo effect differ from the natural course of the disease under study?
Wechsler et al carried out a fascinating trial in asthmatic patients comparing acute changes in lung function that occurred after repeated administration of four interventions:
- Masked bronchodilator (inhaled albuterol – otherwise known as salbutamol outside of the US)
- Two placebos – an inert inhaler and sham acupuncture needle
- No treatment
This was a randomised double-blind crossover study. 46 stable asthmatic patient were recruited and received each of the four interventions on 3 separate occasions, a total of 12 treatment visits over the course of a year. Patients were asked to rate their degree of symptomatic improvement on an visual analogue scale after receiving the intervention as well as undergoing spirometry to assess their FEV1 (maximum forced expiratory volume in the first second). Spirometry was undertaken before the intervention as baseline and was then repeated at 20 minute intervals for the next two hours.
- Patients recorded statistically significant symptomatic improvement with all three treatment-based interventions when compared to the no treatment group. Interestingly there was no statistically significant difference in the symptomatic improvement provided between the active albuterol inhaler and the placebo inhaler (P=0.12)
- Spirometry showed that only the active albuterol was effective in improving lung function. Patients experienced an average improvement in FEV1 of 20.1% with the blinded albuterol, whilst for placebo inhaler it was 7.5%, 7.3% with sham acupuncture and 7.1% with no treatment control
The patient’s own subjective evaluation of intervention effectiveness differed considerable from the objective spirometry results. The author’s conclusions:
Although albuterol, but not the two placebo interventions, improved FEV1 in these patients with asthma, albuterol provided no incremental benefit with respect to the self-reported outcomes. Placebo effects can be clinically meaningful and can rival the effects of active medication in patients with asthma. However, from a clinical-management and research-design perspective, patient self-reports can be unreliable. An assessment of untreated responses in asthma may be essential in evaluating patient-reported outcomes.
We will be discussing this fascinating paper at 8.00pm BST on Sunday