Open questions
Everything this document says it does not know, collected in one place. A reference that publishes its own gaps can be checked against them, which is the point of publishing them.
This category is heavily promoted and thinly evidenced. A reference that says so is more useful than one that does not, and a reference that lists exactly which questions are open is more useful still, because it can be argued with.
If you know of published work that answers any of these, we would like to hear about it. The contact page exists for that purpose, and a correction is not a defeat. The editorial standards page sets out how corrections are handled and how they are recorded.
Chapter 01. The substance
Whether the chain length band a manufacturer targets makes any clinically detectable difference to results in human skin.
How long the injected material actually persists in human dermis before it is fully degraded.
Whether the water binding effect and any biological effect can be separated in a person, or whether the early visible change is simply local swelling.
Whether products that combine polynucleotides with hyaluronic acid behave like either component alone.
The actual residual protein content of products on the UK market, batch to batch, in a form a patient could see.
The true rate of allergic reactions, given that reporting in this sector is voluntary and incomplete.
Whether any difference exists between source species in practice, since no comparative human work is available to us.
How much of the product sold in UK clinics comes through fully traceable distribution.
Whether fragment length within the ranges used commercially affects clinical outcome at all.
Where the boundary between PN and PDRN should be drawn, since no agreed standard exists.
How much of the mechanistic account offered for cosmetic PN treatment survives if the PDRN literature is set aside.
Whether viscosity differences between preparations affect anything beyond how the product handles at the point of injection.
How many polynucleotide treatments are carried out in the United Kingdom each year, since no register exists.
What proportion of adverse events in private cosmetic practice are ever reported to anyone.
What clinical evidence sits inside the technical files of individual products, since those files are not public.
How many products in UK circulation have no UK regulatory route at all.
Whether polynucleotides outperform, match or underperform hyaluronic acid skin boosters on the same outcomes.
Whether combining the two in one session or one syringe adds anything over either alone.
How long any effect persists after the injected material has been cleared.
Whether an unwanted polynucleotide result can be managed by anything other than waiting.
What proportion of UK practitioners have read the instructions for use for the product they inject.
How much of the product circulating in the UK aesthetic sector comes through fully traceable distribution.
Whether asking these questions changes anything about the treatment a patient subsequently receives.
What proportion of consultations volunteer the absence of a reversal agent without being asked.
Chapter 02. Mechanism and evidence
How much adenosine is actually released in human dermis after a treatment, and for how long.
Whether fibroblast activity measurably changes in treated human skin, as opposed to in cell culture.
Whether any measured matrix change is large enough to account for what patients report seeing.
How much of the early visible change is simply local water retention.
Whether anything at all is detectable once the material has certainly cleared.
Whether any independent, adequately powered, blinded, controlled trial of cosmetic polynucleotide treatment exists that we have failed to find.
What the effect looks like at time points well past the clearance of the material.
How results compare against an active comparator such as a hyaluronic acid skin booster.
How much publication bias affects this literature, since studies with null results in cosmetic medicine are rarely published.
Whether outcome measures used in this field track anything a patient would notice.
Whether any measurable effect remains once the injected material has certainly been cleared.
How the treatment performs against an active comparator such as a hyaluronic acid skin booster.
Whether results differ by age, skin type, sun damage history or treatment area.
How much of the visible early change is local water retention rather than anything biological.
What the optimal number of sessions or interval between them is, as distinct from what manufacturers suggest.
Whether a maintenance schedule is necessary or is a commercial convention.
The true rate of complications, since there is no denominator and reporting is voluntary.
Whether repeated courses over years carry any cumulative effect, favourable or otherwise.
How often lumps or prolonged swelling occur in the periorbital area specifically.
Whether people with autoimmune conditions, on immunosuppression or with a history of granulomatous reaction respond differently.
What the residual protein content of products actually is, batch to batch.
Whether allergic reactions occur at a rate the current reporting system would detect.
Whether fragment length within the commercial range affects anything clinically.
Whether combination products behave like either component alone.
What clinical evidence sits inside individual products' technical files, which are not public.
How much product in UK circulation has a UK regulatory route and full traceability.
How many treatments are performed in the United Kingdom annually.
What proportion of practitioners injecting it hold a healthcare registration.
Whether the licensing power in the Health and Care Act 2022 will be commenced, and in what form.
How much of the promotional material currently in circulation would survive an ASA investigation.
How much of the material cited in UK clinic marketing for this category would survive being checked against its source.
How often studies in this field are registered before they start, which would allow outcome switching to be detected.
How many negative or null studies in cosmetic injectables exist and were never published.
Whether patient satisfaction in this field tracks anything measurable about the tissue.
Where the most frequently repeated duration figures in this category originally came from.
Whether any UK clinic publishing a satisfaction rate for this treatment could produce the underlying method.
Whether readers make better decisions when given a qualitative verdict rather than a number.
How many of the figures in circulation would survive being traced to a primary source.
What concentration of the injected material actually reaches fibroblasts in human dermis, and for how long.
Whether laboratory effects on fibroblasts occur at concentrations achievable in living tissue.
Whether findings in rodent skin transfer to human skin in this specific context.
Whether the wound healing models that dominate the preclinical literature are relevant to cosmetic use at all.
Chapter 03. The course of treatment
Whether a course produces more than a single session does.
Whether the interval between sessions matters at all within the ranges used.
Whether maintenance sessions preserve anything, or restart a short lived effect each time.
Whether combining polynucleotides with other treatments in one session adds anything over doing either alone.
Whether stopping partway through a course leaves you worse off than not starting, which nobody appears to have studied.
Whether results differ meaningfully between treatment areas, which nobody appears to have compared directly.
Whether the neck and decolletage respond at all in the way the face is claimed to.
How often prolonged swelling occurs in the periorbital area relative to other areas.
Which hair loss conditions, if any, scalp injections might be relevant to.
How commonly UK practitioners treat outside the manufacturer's stated intended use, and whether patients are told.
How often prolonged periorbital swelling occurs after this treatment.
Whether it is more common with polynucleotides than with other injectables in the same area.
What predicts it, and whether anyone could be screened out in advance.
Whether any intervention shortens it, given there is no reversal agent.
Whether the treatment addresses any component of under eye appearance other than skin texture.
How long visible signs actually last, by area, since nobody appears to have recorded it systematically.
What proportion of patients bruise, and what predicts it.
Why periorbital swelling persists longer in some people than others.
Whether any aftercare measure shortens recovery, as opposed to being customary.
Whether any of the customary restrictions actually change outcomes.
Why clinic aftercare lists differ so widely in duration and content.
Whether massage after treatment helps, harms or does nothing, since advice points both ways.
What the actual infection risk is after multiple dermal punctures in a clinical setting.
Whether any effect persists after stopping, which is the same open question as the rest of this document.
What repeated courses over many years do, favourably or otherwise.
Whether a rebound effect exists, which nobody appears to have looked for.
Whether people who stop and restart respond as they did the first time.
Chapter 04. Safety and candidacy
Whether people with autoimmune conditions respond differently or experience more adverse events.
Whether immunosuppressive medication changes the infection risk of this specific procedure meaningfully.
Whether a history of keloid scarring predicts any problem after multiple dermal punctures.
What proportion of consultations in this sector end in a decision not to treat.
Whether people with body image concerns are being identified at consultation at all.
The actual frequency of any complication of this treatment in the United Kingdom.
How often persistent nodules occur and what distinguishes those that settle from those that do not.
Whether vascular events occur at a different frequency with this material than with others.
What proportion of adverse events in private cosmetic practice are ever reported to anyone.
Whether biofilm plays a role in late presenting nodules after this treatment.
Actual residual protein content in products on the UK market, batch to batch.
Whether allergic reactions to these products occur at a rate the current reporting system could detect.
Whether people with severe fish allergy have been studied in this context at all.
How often the fish origin of the material is disclosed at consultation without being asked about.
The rate of infection after cosmetic injectable procedures in the United Kingdom.
How much of the variation in complication risk is attributable to setting rather than to material.
Whether the licensing power in the Health and Care Act 2022 will be commenced, and what it will cover.
How many providers currently operate outside any premises inspection regime.
How many people who experience a complication after a private cosmetic procedure end up in NHS care.
What proportion of providers offer a genuine out of hours contact route.
How many complications are never reported to anyone at all.
Whether the licensing power in the Health and Care Act 2022 will be commenced, and what redress it would create.
Whether autoimmune conditions change outcomes or adverse event rates for this treatment specifically.
What the correct interval after systemic acne treatment actually is, since practice varies and rests on convention.
How previously placed materials interact with a new injectable in the same area.
How often histories are taken in a way that changes the plan rather than being filed.
Chapter 05. Regulation
What proportion of practitioners offering this treatment in the United Kingdom hold a healthcare registration.
Whether outcomes differ by practitioner background, which nobody appears to have measured.
Whether the licensing power in the Health and Care Act 2022 will be commenced and what it will require.
How many providers fall outside any premises inspection regime.
Whether regulations under section 180 will be made, and when.
Which procedures would fall within scope of any scheme.
What training or qualification standard a personal licence would require.
How a scheme would be enforced and resourced by local authorities.
What would happen to practitioners already operating who could not meet the standard.
How common remote prescribing arrangements remain in UK aesthetic practice.
What proportion of practitioners offering injectables can access urgent prescription medicines when needed.
Whether the absence of a reversal agent changes what emergency medicines a practitioner should hold.
How many practitioners have a written emergency protocol as opposed to a general intention.
How much of the polynucleotide marketing currently in circulation would survive an ASA investigation.
How many complaints about this category the ASA has received.
Whether unfalsifiable category language such as regenerative can be addressed by the Code at all.
How much social content about this treatment is incentivised and undisclosed.
Whether any prosecution or judicial decision has addressed the scope of the 2021 Act in relation to products of this kind.
How the exception for registered health professionals is being applied in practice.
How much cosmetic treatment content reaching under eighteens on social platforms is undisclosed advertising.
How the equivalent position stands in Scotland, Wales and Northern Ireland.
What proportion of UK providers of this treatment fall within any premises regulator's scope.
What proportion of non registered practitioners hold indemnity insurance.
How many local authorities operate special treatment licensing that would cover these procedures.
How often patients successfully obtain redress after a complication from a private cosmetic procedure.
Chapter 06. Deciding
What proportion of consultations in this sector result in a decision not to treat.
Whether free consultation models produce different recommendations from paid ones.
How often the possibility of no visible change is mentioned at consultation.
How often the absence of a reversal agent is volunteered rather than asked about.
How often the absence of a reversal agent is included in consent discussions for this treatment.
How often patients are told that no visible change is a possible outcome.
How often the unresolved status of the central claim is disclosed at consultation.
Whether patients who receive a full consent discussion report different satisfaction from those who do not.
Whether patients who ask these questions receive different treatment or different outcomes.
How many practitioners could answer the product questions without checking.
How common commission structures are in UK aesthetic practice.
Whether informed questioning at consultation changes anything at all about what follows.
How any of these treatments compares with any other on the same outcomes in the same people.
Whether combining them adds anything over using one.
What the regulatory status of individual exosome products in the United Kingdom actually is.
Whether preparation variability makes platelet rich plasma studies comparable with one another at all.
What the treatment actually costs across the UK market, which we deliberately do not publish.
Whether package purchasing changes how many sessions people ultimately have.
How commonly finance is offered at the point of decision in this sector.
How many people continue maintenance for years without reassessing whether it is doing anything.
How many people who consider this treatment decide against it, since nobody counts.
Whether people who decline report any different outcome from those who proceed.
How much of the demand for this category is generated by undisclosed incentivised content.
Whether the licensing position in England will change the market at all.
Revisions to this document
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