Hb level [Design Issues]

posted by Ohlbe – France, 2019-12-29 17:04 2a01:e34:eccb:f980:209d:fce8:64d3:fb12 – Posting: # 21033
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Dear Chirag,

Some thoughts, in addition to what ElMaestro already wrote.

» The list of laboratory reference ranges or intervals are included in Appendix 5. Please note that as this study is conducted in healthy volunteers, subjects should be recruited into the study only if their health is fully verified, including verification that serum biochemistry and haematology parameter values are within pre-defined normal ranges. The enrolment of a subject with measured values for the health verification parameters that fall outside the pre-defined site normal values should not occur, except on a rare, exceptional basis. On the rare occasion when a subject is enrolled in a study despite having a measurement outside the site normal range, the study physician should have a clearly documented and medically rigorous justification for making that exception.

I do not know whether the use of different terms by the WHO is intentional or not, but it certainly adds to the confusion.

» Good Clinical Practices (GCP) require that the rights, safety, and well-being of trial subjects be given top priority in every trial conducted.

Absolutely. And that's why I'm not too comfortable with this:

» To cite an example
» A. Laboratory Reference range for Haemoglobin - 13-18 g/dL
» B. Pr-defined Site Normal range for Haemoglobin - > 12.5 g/dL
»
» B has been set by the physician at his/her own discretion
»
» Can "B" value be used for enrolment of a volunteer into the study

It is fairly common for healthy volunteers in India to have a Hb level below 13 g/dl (I'd even say that based on ElMaestro's definition of "5% of normal folks are outside of the normal range", the normal range used by many labs in India does not seem to have been adapted to the population they usually serve). You can live a perfectly normal life with a Hb level between 12.5 and 13 g/dl. Where I become somewhat uneasy is that you are going to collect a few hundred ml of blood from these subjects. And that ethically and in the subject's best interest, you should avoid doing this from subjects who already have a borderline low Hb level. In France, you can only do a blood donation if your Hb level is at least 14 g/dl. I don't know whether there is an official limit in India.

Another aspect, again specifically for Hb: this can also be an indication of over-participation in BE trials / CRO shopping. I do not trust 100% the databases (OVIS and the like) which have been put in place against this.

This being said, and while mentioning Hb and collecting a large amount of blood from the subjects: many bioanalytical labs still use 500 µl of plasma when developing their methods, just like in the old days of HPLC/UV and though their LLOQ is now 3 logs lower thanks to LC/MS-MS. Using just 50 µl of plasma would be enough in most cases, which would allow to significantly reduce the blood volume collected (e.g. 2 ml per sample instead of 5), while keeping the possibility to re-analyse the samples multiple times if needed.

Regards
Ohlbe

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