Re: 7 days left to comment (was Re: representing potential drug-drug interaction knowledge and evidence - Last commenting period for the W3C Community Group report

Dear Rich,

Thank you for your helpful responses to my comments. As I mentioned before, my concerns are largely peripheral to the model itself although it's great to now have a visual representation of the model included in the report.

Much as I respect the expertise of your group, I cannot accept that the potential bioavailability of ophthalmic formulations of diclofenac is the same as systemically administered formulations (and therefore, if I've understood you correctly, suitable to be grouped together as "NOT topical diclofenac"). The UK Summary of Product Characteristics for Voltarol Ophtha Multidose Eye Drops states, "No measurable levels of diclofenac could be found in humans after ocular application of diclofenac sodium eye drops". The FDA-approved SPL for Diclofenac Sodium Ophthalmic Solution 0.1% states, "Results from a bioavailability study established that plasma levels of diclofenac following ocular instillation of two drops of Diclofenac sodium ophthalmic solution, 0.1% to each eye were below the limit of quantification (10 ng/mL) over a 4-hour period. This study suggests that limited, if any, systemic absorption occurs with Diclofenac sodium ophthalmic solution". Gold Standard's Clinical Pharmacology text summarises the pharmacokinetics of ophthalmic diclofenac by saying, "Systemic absorption from the ophthalmic formulation is not clinically significant". Perhaps I've misunderstood your assertion but anyway, you are quite right to point out that the report presents exemplars.

I agree that references to drug classes need to be accompanied by definitions that allow users or readers of the system to unambiguously understand the membership of those classes.

I take your point about presenting a more comprehensive level of drug information but to do so with clarity will require a complex implementation. Given your scenario of warfarin + topical diclofenac the user (be that a system implementer or a clinician) is presented with:


  *   Drugs involved: warfarin + NSAIDs


  *   Mechanism of interaction: Antiplatelet effect of NSAIDs increases bleeding risk


  *   Clinical consequence: Increased risk of bleeding including GI bleeding, intracranial haemorrhage, cerebral haemorrhage


  *   Seriousness: Serious


  *   OCS: No special precautions


  *   Evidence: Topical diclofenac has low systemic absorption

So it needs to be made clear to the user that most of this information does not apply. The key piece of information here is the Evidence because without that the OCS appears to be inconsistent with everything else presented. But, according to your model, Evidence isn't a mandatory data item. I think this approach represents a risky strategy. The lower-risk approach would be to ensure the drugs involved are precisely defined (e.g. warfarin_systemic + diclofenac_topical) and then present correspondingly appropriate mechanism, consequence, etc information. If someone (for whatever reason) chooses not to bother with the Evidence, they have still got a clinically accurate set of data.

Kind regards
Colin Macfarlane

Colin Macfarlane
Medicines Optimisation Team Lead
ELSEVIER | Clinical Solutions