Use of invasive placebos in research on local anaesthetic interventions

Abstract

Placebos play a vital role in clinical research, but their invasive use in the context of local anaesthetic blocks is controversial. We assessed whether recently published randomised controlled trials of local anaesthetic blocks risked harming control group patients in contravention of the Declaration of Helsinki. We developed the 'SHAM' (Serious Harm and Morbidity) scale to assess risk: grade 0 = no risk (no intervention); grade 1 = minimal risk (for example, skin allergy to dressing); grade 2 = minor risk (for example, subcutaneous haematoma, infection); grade 3 = moderate risk (with or without placebo injection) (for example, neuropraxia); and grade 4 = major risk (such as blindness, pneumothorax, or liver laceration). Placebo interventions of the 59 included trials were given a SHAM grade. Nine hundred and nineteen patients in 31 studies, including six studies with 183 children, received an invasive placebo assessed as SHAM grade ‡ 3. A high level of agreement (78%, j = 0.80, p < 0.001) for SHAM grades 0-4 increased to 100% following discussion between assessors. More than half of the randomised controlled study designs subjected patients in control groups to risks of serious or irreversible harm. A debate on whether it is justifiable to expose control group patients to risks of serious harm is overdue.

A randomized controlled trial comparing intrathecal morphine with transversus abdominis plane block for post-cesarean delivery analgesia

“…Secondly, fluid distension of tissue planes may result in a mechanical or other response that might affect postoperative pain requirements. 12 Although pain scores were higher in patients receiving TAP blocks, they were within a range deemed acceptable by post-cesarean delivery patients according to a recent study. 13 In that study no women with a pain score <6/10 requested additional analgesia for pain and <10% described the pain as bothersome.…”

“…There are two reasons for using a sham block. The first is the concept that research should not put women to any unnecessary risk, as discussed by McGuirk et al 12 While the risks of a TAP block are low, introduction of a needle into tissue always carries a risk of bleeding, infection and damage to surrounding structures. The use of spinal anesthesia for surgery meant that women already had altered sensation over their abdomen, and we believed pushing a capped needle against the skin was sufficient to provide blinding.…”

Analgesic Efficacy of Paravertebral Bupivacaine During Percutaneous Nephrolithotomy: An Observer Blinded, Randomized Controlled Trial

“…The fact that control group patients are often exposed to harm for the sole purpose of blinding has been highlighted in a review by McGuirk and coworkers. 19 The PVB catheters were taped to the back and not easily apparent in this study. To decrease bias in pain assessment, however, objective measurement of the PCA fentanyl consumption was considered in addition to VAS scores.…”

The case for invasive placebo – is the devil in the detail?

“…Pre-operative hypertension (Table 1) [1] is associated with an increased risk of peri-operative cardiac events and/or mortality (for example [2][3][4][5]); however, its omission from various risk stratification algorithms, such as the Revised Cardiac Risk Index [6] amongst others, has precipitated a fall in profile of this condition. This fall in profile is at odds with its frequency.…”