Ask what the vehicle arm did
In sixteen controlled trials now in this register, between 3% and 58% of people improved on the base cream or the placebo tablet alone. Not one compounded product sold direct to consumers has ever published that number, because not one has ever measured it.
Every controlled trial has two arms. One gets the drug. The other gets the identical product with the active removed, applied on the same schedule, by people attending the same appointments and following the same instructions. The second arm is the only thing that converts a result into evidence, and it is the number the consumer end of this market has never once printed.
Here is what the base alone achieved across the approved products in this register.
The spread is enormous and it is not noise. In photoageing, nearly four people in ten improved on sunscreen, sun avoidance and a plain emollient. In rosacea, a third succeeded on foam base and instructions. In acne, the vehicle response ran from 3% to 17%. In one melasma comparator arm, nobody cleared at all.
What the vehicle arm is actually made of
It is tempting to file this under placebo and move on. That is the wrong reading, and the Finacea trials show why. Subjects in both arms were instructed to avoid the foods and drinks that provoked their own flushing, and to stop using soaps, alcohol-containing cleansers, tinctures, astringents, abrasives and peeling agents for the duration.
A third of the rosacea vehicle group succeeded on trigger avoidance, stopping their irritants, and applying a bland base twice a day. That is not placebo. That is treatment.
Renova's vehicle arm is the same story in a different condition. Every subject in every arm was on a comprehensive skin care and sunlight avoidance programme including sunscreen, protective clothing and a non-prescription emollient. Thirty-nine per cent improved on that alone, and the label says so in the indication section itself.
So the vehicle arm bundles four things: the base cream, the behavioural instructions, the removal of whatever the person was doing before, and the attention of being in a trial. Three of those four are free.
Why nobody selling direct will ever show you one
Running a vehicle-controlled trial means manufacturing an identical inactive product, recruiting hundreds of people, randomising them, blinding the assessors and accepting in advance that the answer might be small. It costs millions and it can embarrass you. Nothing requires a compounding pharmacy to do it, and no compounded product in this register has.
What appears instead is the day-30 satisfaction survey: 74%, 79%, 80%, 81%, 88%, 90%, 91%. Uncontrolled, unblinded, self-assessed, by paying subscribers, at a timepoint before most of these drugs have finished working. Those figures are not lies. They are measurements of a different thing — how people who bought something feel about it a month later — presented in the visual grammar of a clinical result.
The comparison that makes the point is Tri-Luma. Investigator-assessed complete clearing of melasma at eight weeks: 38% in the better trial, 13% in the other. Compounded melasma products advertising 74% to 91% are not outperforming it. They are not measuring the same thing, and one of them has a control arm.
39% improved on vehicle; the drug reached 60%. The gap is the drug.
Vehicle arms at 23.4% and 32.5%, achieved largely by trigger avoidance.
Erythema on vehicle, 15.4%, exceeded erythema on drug, 12.2%.
The comparator arm without hydroquinone cleared nobody at all in trial 1.
A 91%-by-day-30 self-report, for a retinoid the same page says takes six to eight weeks.
The practical version
Two things follow for anyone buying skincare, prescription or otherwise.
- Do the vehicle arm first. Daily sunscreen, sun avoidance, stopping the astringents and abrasives, identifying and avoiding your own triggers, and one bland moisturiser applied consistently. In these trials that combination produced success in between a quarter and four in ten people, depending on the condition. It is free, and every drug in this register was tested on top of it.
- When a percentage is quoted at you, ask what the other group got. If there was no other group, the number is a description of customers rather than a measurement of a drug — and it should be read that way regardless of how large it is.
We will keep publishing the vehicle arm alongside the drug arm in every review of a product that has one, and keep noting the absence in every review of a product that does not. It is the single most informative figure on a label and the one nearest to being free.
EVERY FIGURE IN THIS ENTRY IS DRAWN FROM THE REVIEW REGISTER OR A CITED SOURCE. RECORD NUMBERS RESOLVE. NOT MEDICAL ADVICE.