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Skip to 0 minutes and 5 seconds So we know that any drug has a level at which it becomes effective and at a level at which it becomes harmful, and sometimes the margin between the two is very, very close, so that when you’re hitting the efficacy point you’re also very close to hitting the harmful point. So for instance, the the drug might be beneficial at ten milligrams but if you reach eleven milligrams then the drug is very, very difficult to use. In an ideal world, we would like a drug where you could give a large, very effective dose and have very little harm, or no harm whatsoever, and that would be great because you would say that has a wide therapeutic index.

Skip to 0 minutes and 52 seconds It has a huge margin between benefit and harm but if you have a narrow therapeutic index then the boundary between benefit and harm is quite blurred and you could slip in into harm very easily.

Skip to 1 minute and 13 seconds Well it’s it’s interesting in oncology, because you’re dealing with a life-threatening disease, you want to give something known as the maximum dose to achieve efficacy, and it’s almost inevitable that you will get harm at that dose, so you’re prepared to make quite a lot of sacrifices in terms of harming the patient, so that you can achieve your goal of destroying the tumour and saving the patient’s life. So that’s why, in oncology, a lot of toxicity is acceptable because of its a high-stakes game.

Skip to 1 minute and 46 seconds And I think the oncologists get some reassurance that the drug’s actually working at that point, rather than giving a drug at a low dose with no toxicity and then ultimately, three or six months down the line, finding that it has had no benefit for the patient at all and they might have succumbed to their cancer.

Narrow therapeutic index

Watch this video in which Professor Yoon Loke explains the term narrow therapeutic index and the challenges of choosing a chemotherapy dose that gives the most acceptable balance between benefit and harm.

Professor Loke is convenor for the Cochrane collaboration’s Adverse Events Methods Group.

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Using Personalized Medicine and Pharmacogenetics

UEA (University of East Anglia)