Funding of drugs and clinical trials.

[Kiwidi]

Can anyone explain to me the role that pharmaceutical companies play in deciding which drugs are funded by a particular country? From what I can see individual agencies within each country bargain with them to get drugs at the lowest possible price. I would also like to know what part those companies play in clinical trials and what process is used to decide when and where those trials take place?

[Skyshark]

I don't know.

In the UK I would expect they pay for all the drugs and testing. As the trials protocol isn't approved by NICE the NHS can't deliver it or any part of it.

There was someone from US about a month ago that was asking about funding of A+O for a phase 1b Trial drug+A+O. Seems the drug company were only going to pay for the drug they supplied and not the whole regime. At US list prices for a year of A+O it would be around $250k.

If they moved the whole trial from the single site in Ohio to UK the A+O would be about £80k at list prices without the NHS discount.

[wellbeingwarrior]

First question - none. They are a supplier, the country is a buyer.

Yes the individual country negotiates the price off the supplier (in our case Pharmac).

Second question I can’t answer. There will be research protocols around new medicines becoming part of drug trials. Usually the approval of these are preceded by successful animal trials. That is the game of thrones medical research currently rests on.

[SERVrider]

Most large pharmaceutical companies are multi-national so they may carry out research in several countries at once. I met a pharmacist who had done a lot of development work on Acalabrutinib when doing his Master's degree in the UK while AstraZeneca is domiciled in Sweden and Acalabrutinib was first released in the USA. Marketing decisions will be taken by a different bunch of people from the scientists who developed a medicine.

My son-in-law worked on a clinical trial for tiny implanted radioactive pellets to treat macular degeneration. Part way through the trial was abandoned not because the treatment didn't work but because it wasn't reckoned to be financially profitable.

[SeymourB]

Kiwidi -

Trials are a multi-year process. It usually takes several years to plan before a trial starts.

Each jurisdiction has requirements for documentation of effectiveness, so trial diesign is aimed at satisfying that, first of all.

The cost of running trials makes the pharmaceutical company pick which jurisdiction to pursue. They consider the size of the market, and make an educated gamble on market size.

Jurisdictions know all this, and some simply rubber stamp approval trials done in other jurisdictions.

Some do factor cost into approval for state provided medication, while allowing the sale for self-pay or insurance pay. We see this in the U.S. with FDA approval for general sale coming before Medicare approval for reimbursement for retirees. So, in the U.S., the age of the market is a factor.

All that said, the government agencies, pharmaceutical companies, and medical societies are in constant contact about making the process easier or more effective for either the agency or company. For example:

cllsociety.org/2023/07/cll-...

Patient participation in medical societies gives us a voice in meeting needs beyond simple overall survival.

We're also seeing strategy shifts toward fixed duration combination therapies instead of long term monotherapy. There's growing push back from patients on long term immune system adverse effects that's leading to avoiding CD20 combos, and documenting BTKi and BCL2 combo effectiveness.

=seymour=

[Kiwidi in reply to SeymourB]

Thank you so much Seymour. Very informative reply.

[AussieNeil Partner Administrator in reply to Kiwidi]

To which I'd add that some jurisdictions recognise the importance of encouraging research into the less common (so called orphan disease) conditions, providing tax breaks etc, for the development of drugs for these otherwise less profitable markets. CLL is recognised as an orphan disease in the USA and EU for example. Also, after criticism years back about how long it took for new cancer treatments to be approved by the FDA's standard approval process, the FDA introduced an accelerated approval process, which has been effectively used for the approval of many of the recent targeted therapy CLL drugs.

The tough, and hence lengthy and expensive clinical trial processes now used throughout the world, are the result the massive tightening up of the clinical trial processes that resulted in the Thalidomide disaster. Some drug companies have still been caught out manipulating the approval process, resulting in drug approval withdrawals, which of course means a further tightening up of the approval processes.

With respect to how approved drugs in other countries are approved, as Seymour noted, "some simply rubber stamp approval trials done in other jurisdictions". There can also be joint collaborative agreements, such as project Orbis, whereby drug approvals in any of Australia, Canada or the USA result in approval in the other two countries fda.gov/about-fda/oncology-... Acalabrutinib was the second drug to receive joint approval through Project Orbis fda.gov/news-events/press-a...

With respect to how an approved drug gets onto the list of subsidised medicines in universal health care countries, (which is most of the world), that varies by country. Newly approved drugs need to show at least equivalence to currently improved medications and ideally a better adverse event profile while costing about the same. In Australia, it's much tougher to get a drug approved if it costs more that around A$55,000 per year per person. The first requirement (at least equivalence) was historically a big sticking point for the Australian approval of ibrutinib, delaying it for several years, because our Pharmaceutical Benefits Advisory Committee, which recommends drugs for listing on our Pharmaceutical Benefits Scheme, was looking for a comparison trial, with the comparison arm being the currently approved treatment (FCR) in Australia at that time. That's why the international ACE-CL-311 trial for acalabrutinib included one arm which was the standard therapy recommended by the treating physician, which in practice was typically FCR or BR.

In Canada, federal approval still needs provincial funding for patients. Chris Dwyer ( Cllcanada ) moved across the country when he needed treatment, because his home province hadn't arranged funding while British Columbia had done so.

In Australia, while health care funding is a state responsibility, the national Medicare system funds Therapeutic Goods Administration approved treatments on the Pharmaceutical Benefits Scheme, with some of Medicare's budget provided by a specific Medicare income tax levy.

Neil

[Kiwidi in reply to AussieNeil]

Thank you Neil for yet another informative reply.