The general adoption of the Double-blind RCT was based on theoretical reason and intuitive attractiveness rather than a compelling body of data Randomization: aim to eliminate unconscious and deliberate human influence Blinding: treatment and analysis of outcomes are not colored by prejudice Where is the evidence that our evidence is real?
Primary empirical evidence for the objectivity of the double-blind RCT lies in the differential outcomes it detects compared with other research designs The more rigorous the methods the less efficacious the treatment
SINGLE- BLIND PILOT STUDYDOUBLE BLIND PILOT STUDY 19 patients demonstrated that the cardiac drug Khellin was dramatically better than placebo pill 39 patients demonstrated no difference between the two groups The history of the innovation of blinding starts well before this in the 1700’s with a debate about mesmerism; but in contemporary medicine this is the sole piece of data that began the adoption of our modern arguments From 1960-1970 many other reports mostly in the psychiatric realm continued to see less efficacious treatments with the blinded approach and further used this as validation of the RCT approach Whats the take away point?: RCT’s produce smaller efficacy thus are more true
Post 1970’s metanalysis: “the unpredictability paradox: review of empirical comparisons of randomized and non-randomized clinical trials” – kunz Objective To summarise comparisons of randomised clinical trials and non-randomised clinical trials, trials with adequately concealed random allocation versus inadequately concealed random allocation, and high quality trials versus low quality trials where the effect of randomisation could not be separated from the effects of other methodological manoeuvres
Eleven studies that compared randomised controlled trials with non-randomised controlled trials (eight for evaluations of the same intervention and three across different interventions), two studies that compared trials with adequately concealed random allocation and inadequately concealed random allocation, and five studies that assessed the relation between qualityscores and estimates of treatment effects, were identified. Failure to use random allocation and concealment of allocation were associated with relative increases in estimates of effects of 150% or more, relative decreases of up to 90%, inversion of the estimated effect and, in some cases, no difference.
Modified Discrepancy Argument Instead of consistently adjusting for bias in the direction of inflated estimates of effects, the methodological safegaurds of randomization and blinding are now considered the “best protection against the unpredictability… of bias” Note: there are studies that have found observational studies to be more homogenous than RCT’s Thought: Scientific syntax is very persuasive- if you instead of saying double-blinded RCT use the words intentional ignorance RCT does it sound as persuasive?
- Circular Logic: “the truth is what we find out in such a way” We recognize it as truth because of how we find it How do we know that the method is good? Because it get at the truth Randomly subjecting a person to a milieu of hidden exposures and then spolighting him or her with relentless observation does not nurture normalcy, nor does it isolate humans from their mental processes. They are not immune to any “unconscious” processes that subvert science
Knowledge that one has a chance of receiving placebo may introduce uncertainty sufficient enough to decrease the magnitude of the response or extreme vigilance increasing its effects “resentful demoralization” – participation may create ambivalence, confusion, passivity and voluntary submission
Trial in where both physician and patient were unaware that they were even involved in a blind RCT France 1990: 30 matched pairs of pt with insomnia DB-RCT 1 group knew of trial for new Benzo with hypnotic effects versus placebo; other group unaware Both groups given placebo only Control group had higher hypnotic activity (p<.05) Does informed consent mitigate the drug?
France: 49 consecutive patient with mild/mod cancer pain randomly chosen to be informed or not informed 25 not informed pts received naproxen and placebo randomly thinking they were under standard of care 18 informed patients entered the identical DB-RCT Informed group placebo and naproxen significantly more effective than any intervention of non informed (placebo even better than naproxen of non-informed) Knowledge can affect placebo and treatment disproportionately!!! If placebo in treatment and non treatment arm are not the same- how can you do any significant analysis???
US study 100 volunteers; all told they would be in a trial receiving placebo or real drug (caffeine) 50 then told they would be in Double Blind RCT (real coffee versus decaff) 50 were deceived saying would receive real coffee Alertness, tension, pulse, BP, certainty of consumed caffeine were monitored Deceptive administration of placebo resulted in higher pulse rate and alertness (p<.05 p<.003) Conclusion: certainty of receiving a drug maximizes effects and doubt diminishes effects
Another caffeine experiment 100 subjects; 3 arms ( informed receive caffeine, informed no caffeine, informed RCT) then all given random caffeine or decaf Results: cognitive states interacted with drug and placebo on several outcome points No caffeine reported less alertness than those told received caffeine or double blind Told caffeine and did not get caffeine reported greater tension Double Blind lower BP than other groups and only reliable discriminate group Conclusion: DB studies may lead to erroneous conclusions about clinical effects of particular drugs
Thank you for letting me enthrall you with my words