jueves, 14 de noviembre de 2013

Linagliptin for the elderly (or Who moved my Lancet?)

Some weeks ago I was writing that my Lancet had changed. Somebody had exerted a kind of evil influence or so. I couldn’t recognize him; he was ill. And I told to myself: "well, maybe he's got a fever, leave him recover himself in peace..."

Very recently, October 26th, The Lancet was publishing a phase III Clinical Trial dealin' 'bout linagliptin in the elderly. I hereby invite everybody to think 'bout the issue, and to throw my writings to the garbage can. I consider the background appropriate: we live in world where the elderly are important and will be more important in the future, specially in Health issues. The article proposes the comparison linagliptin vs. placebo in poorly controlled Type 2 Diabetes using conventional means. And they do so by conventional means - I beg you pardon for the reiteration-: an international Phase III Clinical Trial (including Australia, Canada, Denmark, Holland and Sweden, that's to say only one nation, isn't it?). I can maintain this because more than 96% of subjects participating in the study were whites - no difference between study arms -. A kind of study made for the white nation?

Next issue: linagliptin arm was composed by 71,6% of men, while this figure was only 62% in the placebo arm. Political correction was absent in the present study: whites, proceeding from rich countries, male predominance - we only need to add protestants and well in touch with the Bilderberg Club  -. I acknowledge that my writings can be provo, unscientific and disgusting, and I apologize for that. My style is entirely inappropriate. But it's only a way to attract your attention 'bout the peculiar study representation and the population to whom the study conclusions could be applicable - if at all -.

Next issue: sample size. Listen: this used to be my Lancet and it is assumed that one can pose certain requests. Taking into account that it is a Phase III Clinical Trial centered upon surrogated variables, 162 individuals composing the linagliptin arm and 79 in the placebo arm seem too small a sample for a Lancet paper, don't you think? When I was younger, so much younger than today this paper could aspire to get - if at all – a position in Diabetic Medicine or Diabetes Care - and relying upon strong inner support -. The elderly pose a high risk of events. This way, the fact of accumulating events in a so little time span, makes it relatively easy designing a trial centered in robust end points, not surrogate ones. For old Lancet papers you could either make this or design a longer study in order to provide strong data upon drug safety.

Moreover: old Lancet papers had strict comments that tended to alleviate authors' euphoria. I cannot find it here, as I didn't in the previous canagliflozin paper. Comments are centered upon treatment protocol and other questions as, for example, to be fragile or not. To be or not to be, that’s the question. In any case, the question seems to lie too far from correctly analyzing this paper flaws. Or maybe this is a too stringent comment for a comment. In fact, old comments tended to be very stringent and created a sense of education ‘bout reading a scientific paper. Indeed, I have to thank this to old Lancet comments and I have to say that I do not find it now. But it is just a humble opinion.

Changin’ the scope, it comes to my mind that this study conclusions are applicable only to a very special kind of population, scarcely representative at all of the global burden of disease, even selecting the age subset to which the study is addressed. We’re going to forget minor quibbles as, for example, the tiny gender disproportion between study arms, surprisingly not taken into account – as far as I know - by reviewers and commenters.

Unfortunately, at the light of the present article, I have to put forward my point of view: this is not my old dear Lancet. Somebody or something has changed it. Papers that would have made an acceptable Diabetic Medicine – under a strong criticism from a serious leader writer – have strangely climbed the stairs up to old top-rank journals, making the way for a suspicion that comes and goes into my brain since I decided to write my first novel K.O.L. Key Opinion Leader (still in the Spanish language): if it is The Lancet what they believe, you only need to buy it or rent it… You just need to ask Rupert Murdoch. It’s the easiest way through.


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