I’m seeing conflicting accounts on when allocation concealment via opaque, sequentially numbered, sealed envelopes was first rigorously described; I’ve found the MRC’s 1948 streptomycin RCT used centralized allocation, while Austin Bradford Hill discussed envelope methods in the early 1950s. Does anyone have a primary citation that nails down the earliest proper description, ideally with specifics like opacity, tamper-proofing, and numbering?
I ran into this while auditing an old trial and the clearest early ‘opaque, sequentially numbered, sealed envelopes’ description wasn’t in a paper but in the trial’s pharmacy appendix. Check the MRC/Wellcome Collection finding aids for investigator manuals and SOPs — those appendices spell out tamper‑evident seals and countersignature logs better than the BMJ/Lancet reports do, like the real method hiding in the footnotes: Collections | Wellcome Collection.
I’d check the pharmacy files before the journal reports — our 2009 RCT had the sealed, opaque, sequentially numbered envelopes procedure only in the pharmacist’s randomization SOP, and the 1950s MRC boxes at the UK National Archives had similar memos: https://discovery.nationalarchives.gov.uk; if you want a citable ‘first’, it may be a manual rather than a paper. Are you open to an archive doc instead of a journal citation?
This drives me nuts too! I remember digging through old trial archives and finding that envelope method mentioned in a 1952 report that wasn’t widely circulated. Sometimes it feels like we’re going in circles trying to pin down the exact origin. @jacwils, it’s frustrating when the best accounts are buried in protocol documents, right?