From this Guideline (Guideline on similar biological medicinal products containing monoclonal antibodies – non-clinical and clinical issues):

Comparative clinical studies between the biosimilar and reference medicinal product should always be conducted. The number and type of studies might vary according to the reference product and should be justified based on a sound scientific rationale. A stepwise approach is normally recommended throughout the development programme, and the extent and nature of the clinical programme depends on the level of evidence obtained in the previous step(s). During the clinical development programme, patients are normally enrolled commensurate with the level of evidence obtained from preceding steps which support comparability.

Does this mean "if the level of gathered evidence is high enough for the successful completion of step 1, then patients are enrolled for step 2"?


2 Answers 2


It is not clear whether specific patients are enrolled because they've shown to be promising candidates for the biosimilar in previous clinical tests in which they themselves were involved, or if patients in general are enrolled only when previous clinical tests justify further tests with the biosimilar.

If is the former, the tests would be culling from the population only those patients who have responded favorably to the biosimilar. That might be a valid approach, for identifying the traits which unite those who respond most favorably to the biosimilar would allow the biosimilar to be targeted to a specific subset of the population.

But I think it is probably the latter. Promising results license further clinical tests, and it is not the same set of patients (a subset of them) that moves on from one test to the next.

  • I think it's hazy because it was written by Europeans, who are probably not native speakers of English. Jan 19, 2017 at 12:04
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    I think Patients are normally enrolled commensurate with the level of evidence is the problem. If I've understood the meaning correctly, I'd rewrite as follows: "Only when the evidence from preceding steps demonstrates that the biosimilar is comparable to the reference medicine should patients be enrolled in further clinical tests."
    – TimR
    Jan 19, 2017 at 12:41

This is what I have understood,

In order for patients to be enrolled in these clinical studies, they have to first satisfy certain criteria. The previous step(s) referred to are those previously mentioned in the Guideline; i.e. 4.1 In vitro studies, 4.2 Determination of the need for in vivo studies and 4.3 In vivo studies.

The (s) in step(s) suggests that one or more steps may be taken into account.

The more productive (or positive) the results are (commensurate with the level of evidence), the easier it is to compare those results (support comparability) from the two different studies 1. Non-clinical studies 2. Clinical studies

Therefore, only those patients who meet this requirement are normally selected (enrolled) .

  • But human patients do not participate in "in vitro studies". So it's unclear what "requirement" they should meet. Jan 19, 2017 at 12:01
  • @CowperKettle First of all, you are the expert in this field, secondly, I didn't read the entire guideline. As to whether patients participate in "in vitro studies" I confess I do not know, it does seem unlikely, so I trust your statement. What about the other two steps?
    – Mari-Lou A
    Jan 19, 2017 at 12:05

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