Sunday, 4 December 2011

Controlling Trials

You quote: It must be difficult to justify giving one set of patients the proposed (nutriceutical) drug and another just the placebo when you know they are receiving nothing and the only benefit they will get is the placebo effect, whilst there are DMT's that could help them already on the market.

Remember previous posts such as Do you think placebo-controlled trials are ethical?

Has G changed his mind One Year On?-Probably not, because the promise of effective first-line oral agents has sadly still yet to materialise within the UK, but this is changing elsewhere.

In RR MSers there has been an increasing number of clinical trials comparing active drug typically compared with an injectable such as interferon rather than placebo. This speaks to avoiding an ethical issue of MSer's not gettting no active treatment.

However, it also has to be said that this provides a real marketing oppertunity to show that the new test drug is better than current, competitor drugs. Examples of this could be the efficacy of alemtuzumab over interferon beta. These lack a placebo arm, but are not really double-blinded (MSersand and treating doctor don't know treatment drug) when comparing daily injectables with intravenous injectables. Should we make antibodies infused monthly to go aginst tysabri, which is highly effecicacious? This unlikely to occur as it has the risk to backfire when the test drug has worse efficacy than the current treatment such as occurred with oral laquinimod.

Compared to say interferons/glaterimer acetate that are low hisk-modest gain there are a number of high risk-high gain agents such as alemtuzumab/rituzimab (yet to be licensed) and tysabri it is perhaps easier to see why this trial design of high-risk drugs compared to low-risk drugs occurs, but once we have a low risk-high gain drug especially if it is oral then we may have a game changer. Then it will not only be hard to justify placebo control, but also not having to test drug on top of the low-risk, high efficacy established drug. if the two drugs are say immunosuppressive it may be difficult to show efficacy without increasing the risk of side-effects due to reduction in normal immune function. Therefore, once one of these drugs are shown to be effective and safe, it is going to be hard to knock the drug off its perch and develop new drugs Therefore, it is surprising that pharmaceutical companies are pricing their drugs so high, such that it limits uptake of the drug.

Therefore, there may be a limited window of opportunity to test nutriceuticals such as probiotics and vitamin D that will be of very low risk, but maybe of modest efficacy (based on animal studies) before a pharmaceutical becomes established, first-line treatments


  1. 1. '... but are not really double-blinded ...':
    Isn't it possible to do a trial where everybody gets two treatments without knowing which of the two is real?

    2. 'Then it will not only be hard to justify placebo control, but also not having to test drug on top of the low-risk, high efficacy established drug.':
    Why would it be necessary to test the new treatment on top of the older one?

  2. 1. Yes it possible to do trials where people get one of two placebos. For a beta interferon arm it means numerous injections for 2-3 years and for alemtuzumab would mean infusions plus course of steroids.

    However you have to justify doing 2-3 of pointless injections with placebo when you know the active drug is so superior in terms of efficacy.

    Once one drug is found to be safe and highly efficacious, it will not be ethical to give someone nothing in a trial.

    So it will have to be an active comparitor. The bar for the first generation of drugs is about 30% inhibition of relapse, which is just above the placebo effect. However the new generation of drugs, if say is over 50% effective so if one of these if found safe the bar is raised and this is the new baseline over which you have to show and effect.

  3. Thank you. I misunderstood 'on top of' to mean 'in addition to'

  4. Where do you believe that either BG12 or Gilenya fits in on this scale risk/benefit?

  5. Yes at some stage i think it will be in addition to. This is known as an add on. For example sativex is an add on. If it had been tested on drug naive people against just placebo maybe it would have worked much better than compared to people on active drug.

  6. Bg12v gilenya.
    First point is gilenya is a licensed treatment Bg12 is not yet. Many things can happen.

    In terms of efficacy based on trial data both are oral and both are of high benefit. They appear to be about as effective as each other in Relapsing ms. However if one has better efficacy on progression it could give it one an edge. This would be a marketing potential as results from progressive ms are some years away.

    Now if think about gilenya there is a high risk that you will be seriously out of pocket if you are paying for the drug. IF approved will Bg12 be cartel priced or will it be priced lower to be "Nice" priced. It may get a market share or start a price war.

    In terms of side effect profile it is too early to call but my prediction will be that the risks may be greater than with interferons . Time Will tell there have been more people treated with gilenya than Bg12 but Bg12 is based on drug used lot in psoriasis.
    It will be a better environment if there is choice.

    Coi : none


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