Sunday, 23 December 2012

BPA: why is a drug license necessary?

"Why is a drug license necessary? I posted on this topic last week, under the title off-label prescribing. Each country or region has an agency that licenses drugs; in Europe it is the European Medicines Agency (EMA), in the US the Food and Drug Administration (FDA), in Canada, Health Canada, in the UK, the Medicines and Healthcare products Regulatory Agency (MHRA), etc. These agencies make sure the drug has an appropriate risk:benefit ratio for the target population of patients with a specific disease or subtype of disease. In MS this could be a clinically-isolated syndrome, relapsing-remitting, secondary progressive or primary progressive disease. 

If a license is turned down by the regulators or licensing agencies it generally means they are unconvinced by the risk:benefit ratio of the drug! In other words the drug has too many side effects or undefined risks to warrant its use given it effectiveness, or the drug is not effective. 

A license by an agency is essentially a seal of approval and it then allows the drug to be marketed for its specific indication by the Pharma company concerned. Marketing is important as this allows neurologists to be approached and given information about the drug and its benefits. Without a license you can't inform anybody about the benefits and payers don't have to pay for the drug either. In the UK getting payment for an off-license drug, no matter what it costs, is getting increasingly difficult. In austerity Britain where the NHS has to save £20 billion over 5 years pennies count. Who are the payers? These are the people who decide on whether or not a drug or service is worth paying for; in the UK these are the so called Primary Care Trusts (PCTs), soon to be Commissioners. In other parts of the world payers are Insurance companies or Health Maintenance Organisations (HMOs).

What happens if you market a drug off-license? If the authorities find out the Pharma companies get huge fines. Recently some of these fines have come close to $3 billion. What happens if a neurologist promotes the use of a drug off license? Not much at present, but I if the drug is risky he or she will be putting themselves at risk of a medicolegal challenge. For example, if Dr Chataway started promoting the off-license use of Simvastatin at a dose of 80mg per day for progressive MS on the back of the results of one phase 2 study and an MSer happens to die from developing a rare complication of the treatment. Would Dr Chataway, the MSer or the neurologist who prescribed  the drug be responsible? The courts will decide, but Dr Chataway would definitely have to accept some responsibility. If found guilty it could result in him being sanctioned by the General Medical Council. The point I am making is that we need to have the same level of evidence applied for all drugs for treating MS, we can't simply lower our scientific standards for off patent, cheaper drugs, hoping the community will take up prescribing with a lower evidence base. 

As I get older I realise that scientific research is also a social science; i.e. how do you get the community to adopt you ideas and translate the evidence into clinical practice. Part of getting the neurologists of the world to use drug X for progressive MS is having a good enough evidence-base to convince them. An important part of the evidence base is the seal of approval of regulators. In other words we need to get drugs licensed. You would have more confidence in a licensed drug compared to an unlicensed drug. Or may be I am wrong?"

9 comments:

  1. While I agree that drugs need to be trialled to show efficacy / safety and licensing is the right approach, the difference is the nature of MS. We are not taking toothache here. This is the slow or fast destruction of the brain / spinal cord. Is safety really an issue for Debbie Purdy? Can a person with SPMS wait 10 years for the slow wheels of licensing to turn. If I was your best friend and had SPMS and asked about simvastin would you say come back in 10 years or suggest ways I might gain access to this drug? The system you describe above is fine for non-lie threatening diseases. MS is a life shortening disease which severely reduces the quality of life. We've waited decades for anything that will provide some neuro protection. Several agents look promising yet we are asked to wait a decade or more again. Looks like the fear of litigation overrides the desire to really help patients.

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  2. 'You would have more confidence in a licensed drug compared to an unlicensed drug' - Yes I would, but as the previous comment says, we are short of time.

    If there is good-enough evidence that a drug is useful, and it doesn't cost much, and it is known to be low-risk from long use for other purposes, and there is no proven alternative, then I think it's worth using.

    At the same time, I would expect somebody to work on collecting better evidence and finding better drugs. This unlicensed/unproven use should be temporary.

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    1. I agree with above - am of similar opinion - would love to get a neuro protective drug like simvastatin even with some safety issue. I would take the drug waiting for more safety trials but would like to have the option to get drugs sooner and decide for myself how much risk I am willing to take!

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    2. Why would you go on a trial if you knew that if you didnt you get the drug?

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  3. If you can find me some more white knights it will be much appreciated. It. Is hard to be pharma free, if you are any good pharma will want to hear from you.

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    1. what gives these people the right to pontificate the right over other the life choices of other peoples life ,essentially its a cheap shot and an easy target towards disabled.

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  4. Agree with the need for speed, but fear this is playing Russian roulette with the risks. Great if something does what it says on the tin and we get it sooner. However, for example, had Tysabri been made available sooner, the PML risk would have appeared only as isolated case studies that perhaps wouldn't have been picked as quickly. The push to find ways to assess risk would have taken longer to develop and even more people would have died.

    Make the science faster but not hastier

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  5. So, what happens if you know an off label drug to be safe and the efficacy is anecdotal? I actually use an off label prescription which is at least safe. Also, what research has been done suggests the right biochemical activity to control my MS. So, if I choose to use such a therapy, why should I be refused it? I am an experienced researcher of science so I am confident in my choice, and to be honest, the alternatives for SPMS are too risky for me and I have rejected them.
    So, my point is this, if a drug is low cost and known not to be dangerous even at very high doses, then let me have it if I ask for it!! That is a no brainer and even leaves the existing systems for licensing intact and in most cases, those systems work fine.
    So what is this inocuous drug that needs such attention? It is called Low Dose Naltrexone, and every bit of new research just strengthens the case. Of the 100 thousand or so users, many seem to use it for flawed reasons, like they believe it boosts the immunes system! Well it doesn't, and in fact it is entirely compatible with other options. It stimulates met enkephalin which controls proliferative diseases like cancer or autoimmune diseases by blocking the cells from replicating. A simple process which operates directly on the DNA to block proliferation hence it's alter ego, Opioid Growth Factor.
    So, if we [patients choose to follow our nose with a safe and low cost drug, we need licensing to make exceptions in our favour, and LDN just shows, that any system, however 'perfect', has limits and need exceptio processing from time to time. LDN is such a cause.

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  6. I take Rebif 44 and LDN. I buy my LDN and make it myself from Naltrexone, which I buy from my local pharmacy. I don't know if it's doing anything wonderful for my brain, but it has really helped my bladder. I can sleep through the night now - which I haven't done for 20 years. It's certainly low cost. It's about 30 euros a year for me. My GP knows about this and so does my neuro and as my blood test results are fine, they are happy to let me carry on taking it.
    You can't follow this option in the UK.

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