Do you agree with the BVA on cascade?

RE: Do you agree with the BVA on cascade?

David Mills — Tue, 17 Sep 2024 09:01:57 GMT

[quote userid="9239" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245457#245457"]Great, do we have published evidence that every licenced drug is a better choice for animals than their generic? [/quote]

Quite.

Whenever this discussion comes up industry immediately reach for the "safety" counterargument, conveniently forgetting that human generics have all been tested to toxic levels in animals (rodents, beagles) so we know the safety margin in the species we treat better than we do in humans.

Re efficacy, most licensed these days have to show non-inferiority to others rather than efficacy which is a subtle but important difference (especially when considering some of the marketing).

Again, the UK and EU are a piddling market globally, where most of the globe is not constrained by the cascade. Is veterinary medicine more safe in the EU/UK? No. It is a legal instrument that is pro-pharma, based on vague (non existent) but expedient reasons of safety and efficacy that do not stand up to scrutiny, and designed almost entirely to benefit drug manufacturers. The same could be achieved via patent legislation, which would prevent the reverse-licensing of generics.

I doubt I'll see a change to the cascade in my lifetime - there is simply too much financial and regulatory interest in keeping it as is.

[quote userid="9515" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245450#245450"]I see Veterinary Specials being used daily and often in preference to licensed medication. This is concerning as these products do not go through nearly the same testing as licensed pharmaceuticals and the vets using them don't realise this.[/quote]

Quite, and they slip by the cascade via the ease of application exemption and do not face anywhere near the same scrutiny.

RE: Do you agree with the BVA on cascade?

Rob Loxley — Mon, 16 Sep 2024 21:48:18 GMT

Radio silence from Colin!

RE: Do you agree with the BVA on cascade?

Dinu Catilina — Tue, 10 Sep 2024 08:43:53 GMT

Maybe, but licencing does not guarantee efficacy or long term safety. See the examples of Tralieve and Pardale, where is the evidence that they are better than just tramadol and paracetamol? Where is the evidence that licenced prednisolone is better than off licence prednisolone? There are multiple examples that make the cascade, frankly, a fraud.

[quote userid="28573" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245438#245438"]Its the reason why generic veterinary medicines in development have to undergo testing to demonstrate bioequivalence in order to gain a marketing authorisation. You have to do the work not just make the assumption.[/quote]

Great, do we have published evidence that every licenced drug is a better choice for animals than their generic? Further more, the cascade wants us to use an animal licenced drug first even if not licenced for the species intended. So can we presume that dogs are the same with cats? Is a dog drug better for cats than a human drug? Why and how?

RE: Do you agree with the BVA on cascade?

Sarah Keir — Sat, 07 Sep 2024 09:40:05 GMT

[quote userid="28573" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245438#245438"]veterinary specials is not something you can hang your hat on[/quote]

I see Veterinary Specials being used daily and often in preference to licensed medication. This is concerning as these products do not go through nearly the same testing as licensed pharmaceuticals and the vets using them don't realise this. The Veterinary Specials companies are very good at promoting their products through promotion from eminent members of our profession, rather than evidence. Concerning? It is to me.

https://www.veterinaryprescriber.org/free-articles/veterinary-specials-what-are-they-for

https://www.veterinaryprescriber.org/free-articles/transdermal-thiamazole-are-cat-owners-getting-crucial-safety-information

RE: Do you agree with the BVA on cascade?

Cinzia Gandini — Wed, 04 Sep 2024 13:46:49 GMT

[quote userid="8182" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245442#245442"] I don’t know if this is EU legislation[/quote]

It seems so, quote"

The European Commission (EC) has acknowledged that insufficient authorised VMPs are available for the treatment of every clinical case in every species. Therefore, Directive 2001/82/EC allows, under Articles 10 and 11, veterinary surgeons to prescribe products that are not authorised for the relevant clinical case or for the relevant species - this provision is known as the Cascade. This is a derogation from the main requirement in the EU legislation to use authorised veterinary medicines - therefore the Cascade increases the range of medicines that a veterinary surgeon can use.
In the UK the Veterinary Medicines Directorate (VMD) has fully implemented the Cascade into national legislation under Schedule 4(1) of the VMR.
https://assets.publishing.service.gov.uk/media/5a817bfeed915d74e623283f/VMGNote13.PDF

I also found as New legislation now in force 2024

The Veterinary Medicines (Amendment etc.) Regulations 2024, which amend the Veterinary Medicines Regulations 2013 in respect of Great Britain, are now in force.

Which means it hasn't been removed

https://www.gov.uk/guidance/vmd-information-hub#new-legislation-now-in-force

RE: Do you agree with the BVA on cascade?

Eamon McAllister — Wed, 04 Sep 2024 11:03:46 GMT

The following statements are verbatim extracts from a Dechra Pharmaceuticals Annual Report:

”The Cascade Legislation; the basic principle of this EU legislation is that the Veterinary Surgeon must prescribe a veterinary licensed product above any other alternative. Therefore any products licensed specifically for animals must be used instead of a human ethical or generic product irrespective of price”

”Most of our projects utilise existing pharmaceutical entities that are typically used within the human market and therefore the majority of product creation is development and not research based”

”Development projects have a high probability of success with a relatively low cost; research based projects are usually expensive with a low probability of success”

”After minimal expenditure on early explorative product evaluation an identified human pharmaceutical has a high probability of achieving a veterinary license”

”An identified existing pharmaceutical product can often be brought to full license for the veterinary market within five years”

It is plain from the above evidence that the Dechra business model is based on developing licenses inexpensively for the same drugs that we have been legally prohibited from using, achieving proprietary status and then bringing them to market quickly whilst charging a considerable premium for a relatively small effort.

I don’t know if this is EU legislation but if so perhaps it can be rejected now that that we have Brexit freedoms. It seems to me that this legislation was introduced as a result of concerted and aggressive lobbying by the Pharmaceutical Industry and that the motive was profit and not the welfare of animals.

RE: Do you agree with the BVA on cascade?

Arlo Guthrie — Tue, 03 Sep 2024 10:20:10 GMT

[quote userid="28573" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245438#245438"]In some cases yes.....a good case example is the branded vs generic versions of omeprazole where the generic version was found to have higher bioavailability than the comparator. The formulations are, if not identical, similar.[/quote]

Thank you Colin Capner - I wasn't aware that the different excipients from one formulation to another could have a major effect on the bioavailability of an active. I thought they were inactive (I am a layman!).

I suppose the question that still leaves is that of how significant the effect, both in terms of the number of actives that are affected and to what degree they are affected.

In other words, if the impact on the effectiveness of an active is usually marginal, then it could be a huge amount of cost (borne by the consumer) for little benefit.

[quote userid="4181" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245439#245439"]Or generic Benazecare 20mg costs £77.22 compared to original Forekor 20mg £80.44?[/quote]

Rob Loxley I was going to ask if you happen to know how the price between branded and generic medicines varies in human medicine.

Then I googled it.

Over a four year period, generics are 70-90% cheaper.

Source: https://www.britishgenerics.co.uk/view-news/uk-generic-medicines-market-functioning-well-and-delivering-significant-savings-oxera.html (June 2019)

RE: Do you agree with the BVA on cascade?

Rob Loxley — Tue, 03 Sep 2024 09:23:21 GMT

[quote userid="28573" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245438#245438"]I'm afraid its not the case that you can assume that because two products contain the same active that they have identical effects. Its the reason why generic veterinary medicines in development have to undergo testing to demonstrate bioequivalence in order to gain a marketing authorisation. You have to do the work not just make the assumption.[/quote]

Maybe you can however explain how, having to do much more limited work to bring a generic to the market (based on bioequivalence as you say), the list price of Vitofyllin Tabs 100mg is £35.25 per 56, compared to the original product (which did all the R&D, animal testing, trials etc.) Vivitonin 100mg at £37.23 per 60 tablets?
Or generic Benazecare 20mg costs £77.22 compared to original Forekor 20mg £80.44?
How would you define price gouging? Surely the generic route should give a more significant cost saving to the customer?? I do hope that this is on the CMA radar when looking at how the drug marked works (or doesn't) for the consumer!

RE: Do you agree with the BVA on cascade?

Colin Capner — Tue, 03 Sep 2024 06:19:32 GMT

[quote userid="2100" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245381#245381"]Same question applies to brands of anything really. Is there potentially a significant difference in efficacy between one brand and another containing the same amount of a given active?[/quote]

In some cases yes.....a good case example is the branded vs generic versions of omeprazole where the generic version was found to have higher bioavailability than the comparator. The formulations are, if not identical, similar.

I'm afraid its not the case that you can assume that because two products contain the same active that they have identical effects. Its the reason why generic veterinary medicines in development have to undergo testing to demonstrate bioequivalence in order to gain a marketing authorisation. You have to do the work not just make the assumption.

It is also the reason why substitution of human targeted products or veterinary specials is not something you can hang your hat on to assume same dose and same activity. Formulation matters and the bioavailability of many actives can be substantially affected by how they are formulated or in what circumstances they are administered/consumed.

It may be that working down the cascade is both more convenient and more economic, but cascade is a good principle that ensures the highest reliability that the administered dose is the received dose and effect. Beyond tested medicines uptake can work in both directions as the above example demonstrates. For products with narrower therapeutic indices it could be important and be a source of iatrogenic harm.

For the NHS authorised generics are promoted based upon cost precisely because there is regulation and testing for bioequivalence. None of that applies unless the medicine has been tested within the target species. Often clinical papers make recommendations on products and doses without assocviated pharmacology where they are not used on label. There are many examples where as time passes (sometimes years) it becomes understood that those doses are too high or low, once the pharmacology is investigated. No wonder morphine in the cat was for many years thought to produce mania when doses were around 40mg/Kg. Understanding the pharmacology of morphine in the cat made the drug possible to use.

Modern day examples where the pharmacology may be important but mismatches current clinical use include, tramadol, gabapentin, memantine amongst a number of others. Veterinary pharmacology as a discipline has been at a low ebb in the UK for over a decade now and I think that has been increasingly evident.

RE: Do you agree with the BVA on cascade?

Cinzia Gandini — Fri, 23 Aug 2024 22:12:41 GMT

[quote userid="24356" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245387#245387"]tablet sizes occasionally but does it really make that much difference? [/quote]

In my opinion it does, if a tablet is huge or can't be split maybe is best to look for a more appropriate one. There many veterinary formulations for cats with tablets the size of a papaya that the clients are supposed to give three times a day to their pets.

RE: Do you agree with the BVA on cascade?

Elizabeth — Fri, 23 Aug 2024 21:48:27 GMT

Surely we swap between them all the time when the animal product is out of stock everywhere. There's issues with tablet sizes occasionally but does it really make that much difference?

And this should really be a tangent, but does anyone know why humans seem to get away with much lower prednisolone doses than animals? Are we overdosing or is it different pharmacokinetics?

RE: Do you agree with the BVA on cascade?

Cinzia Gandini — Fri, 23 Aug 2024 19:01:21 GMT

[quote userid="8663" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245380#245380"]My training would not allow me to work out the different pharmacokinetics of alternative brands of phenobarbital (for example) to a licensed product for dogs. Would yours?[/quote]

I’m not sure I got the question but if this might answer you, surely yes, when I started working there wasn’t any phenobarbital licensed for dogs, it was the human Luminal,Luminalettes, and Gardenal tablets and phenobarbital sodium injectable solutions at different dosage. I knew the dosages and the pharmacokinetics from studying pharmacology and the dosage requested for the dog/weight/age and IV/IM/PO and type of use like epilepsy for example...

RE: Do you agree with the BVA on cascade?

Clive Ansell — Fri, 23 Aug 2024 10:29:47 GMT

Yes it would. I would have to revise theoretical pharmacology, and source relevant information, but fairly sure I could come up with and educated and informed opinion.

Surely the chemical, the molecule, Phenobarbitone, is Phenobarbitone, and its chemistry and pharmacokenetics would be the same whoever processed it in to a pill or liquid and branded it?

RE: Do you agree with the BVA on cascade?

Arlo Guthrie — Fri, 23 Aug 2024 09:54:37 GMT

Alasdair Hotston Moore - phenobarbital being one of my specialist subjects (albeit in a human context), I'm very interested in this point.

Would the pharmacokinetics of phenobarbital vary significantly between brands? By significantly, I mean to the extent of requiring a different dose to achieve an effect.

My understanding has always been that it is a VERY blunt tool in the first place, so I would be rather surprised if the there was any measurable difference between one brand and another at the same dose.

Same question applies to brands of anything really. Is there potentially a significant difference in efficacy between one brand and another containing the same amount of a given active?

RE: Do you agree with the BVA on cascade?

Alasdair Hotston Moore — Fri, 23 Aug 2024 08:51:24 GMT

[quote userid="4103" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245292#245292"] thought we were graduated in Veterinary Medicine, and our curriculum was including pharmacology, toxicology, small animal medicine and therapeutics and also including inorganic chemistry, organic chemistry and biochemistry (like in my case). I though we were the ones advising on the content and presentation of pharmaceuticals for animal use.[/quote]

My training would not allow me to work out the different pharmacokinetics of alternative brands of phenobarbital (for example) to a licensed product for dogs. Would yours?

RE: Do you agree with the BVA on cascade?

Cinzia Gandini — Tue, 13 Aug 2024 15:11:30 GMT

[quote userid="8991" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade/245274#245274"]Human medicines and veterinary medicines containing the same active substance may not be interchangeable[/quote]

I thought we were graduated in Veterinary Medicine, and our curriculum was including pharmacology, toxicology, small animal medicine and therapeutics and also including inorganic chemistry, organic chemistry and biochemistry (like in my case). I though we were the ones advising on the content and presentation of pharmaceuticals for animal use.

RE: Do you agree with the BVA on cascade?

David Mills — Mon, 12 Aug 2024 13:41:31 GMT

Interesting some of the reasons that the cascade can be ignored from https://www.gov.uk/guidance/the-cascade-prescribing-unauthorised-medicines

Cascade use when new products come to market

If an authorised veterinary medicine becomes available while an animal is already being treated for a condition under the cascade, you should consider transferring the animal onto the authorised veterinary medicine. However, if you have concerns that changing the product could compromise the stability of the patient’s condition, it may be acceptable to continue treatment under the cascade. Any new cases should receive the authorised veterinary medicine.

Animal owner considerations

You may conclude that an animal owner, perhaps due to age or disability, would have difficulties in administering the authorised product. In the interest of animal welfare and treatment compliance you could consider an alternative treatment under the cascade.

Yet

Human medicines

You are not allowed to prescribe a human medicine simply because it is cheaper than using an authorised veterinary medicine.

Human medicines and veterinary medicines containing the same active substance may not be interchangeable.

None of the above are in the VMR as far as I can see so therefore have no legal basis...

RE: Do you agree with the BVA on cascade?

Kate Richardson — Mon, 12 Aug 2024 12:10:44 GMT

Its nonsense. We " PROMISE AND SOLEMNLY DECLARE that I will pursue the work of my profession with integrity and accept my responsibilities to the public, my clients, the profession and the Royal College of Veterinary Surgeons, and that, ABOVE ALL, my constant endeavour will be to ensure the health and welfare of animals committed to my care" but we can't take costs into consideration when this is probably the biggest limiting factor to ensuring health and welfare of animals.

RE: Do you agree with the BVA on cascade?

David Mills — Mon, 12 Aug 2024 10:24:58 GMT

It's a funny one as we hear it's "legally" not allowed but it isn't in any statute or the code as far as I can see. It seems to stem from VMD pronouncements but hasn't actually been tested in a legal sense. The BVA have perpetuated this misunderstanding and simply linked the code where cost isn't mentioned either.

Given all human generics will have been tested on animals the argument they might not work doesn't stack up either. It's scaremongering. There are many jurisdictions where the cascade doesn't exist and R and D continues apace (America for instance). So again the BVA are wrong about this.

The Vet Times reported a few years ago it was widespread but the VMD openly admitted they didn't have the resources to investigate.

It is a b*S response but not surprising. Given corporate dominance, the majority of BVA members will be from these groups. The rest of the response is pretty much leave things as they are, all vets discuss all options and definitely aren't constrained by KPIs, ATVs and sales performance targets...

RE: Do you agree with the BVA on cascade?

Clive Ansell — Mon, 12 Aug 2024 07:47:35 GMT

No, it's bull****.

[quote userid="12930" url="~/f/clinical-questions/31011/do-you-agree-with-the-bva-on-cascade"]but it would be irresponsible to suggest an unlicensed generic on the basis of cost, especially where that unlicensed product may not work, may result in underdose or overdose, or may even cause harm.[/quote]

How so?

I think any clinician should be able to use their training and experience, to make an informed and educated choice, in full discussion with the client, while at the same time weighing any risks or limitations, as to whether or not using a generic product is appropriate or not.

Would be a change in legislation to decriminalise.

May need clients to sign disclaimers to agree they accept any risks and bear full responsibility.