Point of Inquiry: Dispensing Skepticism

For those interested, I recently spoke with Karen Stollznow for the Point of Inquiry podcast.  What is Point of Inquiry?

Point of Inquiry is the premier podcast of the Center for Inquiry, drawing on CFI’s relationship with the leading minds of the day including Nobel Prize-winning scientists, public intellectuals, social critics and thinkers, and renowned entertainers. Each episode combines incisive interviews, features and commentary focusing on CFI’s issues: religion, human values and the borderlands of science.

This discussion focused on the role of the pharmacist and the need for science-based pharmacy practice. We touched on a lot of issues including the changing role of the pharmacist, the ethical responsibilities of pharmacists when it comes to products like homeopathy, what compounding pharmacies do, what generic drugs are, what an expiry date means, what pharmacists think about vitamins and other supplements, and more. You can listen to the podcast here.

6 thoughts on “Point of Inquiry: Dispensing Skepticism

  1. Had a comment about the podcast re: generic vs. brand name drugs. Your description of the regulation and approval is accurate, but also a little off. You explained that the generic is compared to the drug with the expired patent, and that they must have the same active ingredient, same absorption, etc. The difficulty here is in how the statistics are performed, and as well how the non medicinal components might affect the clinical efficacy.
    My understanding about the statistics is that generics typically need to show non-inferiority, which is not the same as showing equal effectiveness. A superiority trial would demonstrate that the product is not less effective, but it would be unfair to expect a generic to perform better than the product that precedes it.
    Equality could be assessed within some margin, but you can’t show that two samples come from the same distribution (or that the distributions are the same); you can fail to detect a difference. For an equality test, one sets some threshold or distance, and states that the comparator should not lie more than that far from the original. But of course we don’t need a two-sided test, if we only care if the generic is not worse than the original.
    This leaves the non-inferiority test, which doesn’t in fact show that something is non-inferior – it shows that if it is inferior, it’s not more inferior than some cutoff. Deciding on the margin for such a test is tricky.
    So while you are correct that the generic products get assessed, it’s worth noting that they don’t need to prove themselves to be equal to the existing product – just that they are likely not to be worse by more than a set margin.

    • Thanks for the comment. If I wasn’t clear in the discussion then this gives me an opportunity to elaborate on generic drug evaluation.

      The comparative studies used to evaluate generics are not efficacy evaluations or non-inferiority trials. They are bioequivalence trials, examining pharmacokinetic parameters only. They are designed to show a generic version of a product (with the exact same active pharmaceutical ingredient) displays the same rate and extent of absorbtion as the brand (reference) product. The evaluation is therefore a comparison of a drug’s concentration versus time profile following oral administration. (test vs. reference). The measures of interest are Cmax, (AUC|0 to t) and (AUC|0 to infinity).

      Regulators generally require 90% confidence intervals (CIs) of the ratio of the generic and reference for these measures to fall within 80% and 125%. That is, the generic can’t be off in either direction.

      Noninferiority and equivalence trials look at clinical differences from comparators, verifying that the outcome of interest does not vary more (or is less than) than the “equivalence margin”. In the case of generics, variation of any parameter outside the 80% to 125% would lead to a conclusion of generic inequivalence. So while non-inferiority trials are occasionally referred to as equivalence trials, or bioequivalence trials, they are different in design and intent.

    • It’s a very common question. Many are surprised when they learn that there are generally no effectiveness studies conducted to support bioequivalence determinations. Here’s a chapter on bioequivalence[PDF] written by Dr. Jake Thiessen – my pharmacokinetics professor in pharmacy school. It outlines the consideration process far more eloquently (and in detail) that I have done.

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