Dose selection

Question 1

State the importance of dose/
regimen selection

Answer 1

For regulatory agency - considering a new treatment approval
Regulatory agency and ethics committee - considering an application for a clinical trial

Question 2

Principles of Clinical Pharmacology and
Dose

Answer 2

Question 3

What safety factor is most commonly used when determining initial dose in an entry into human study?

Answer 3

10-fold safety dose reduction is applied following estimation of a human equivalent dose (HED). The HED is estimated from body surface area scaling of the no observable adverse effect level (NOAEL) in the toxicology studies.

Question 4

A drug company is planning a phase 2 study to determine the doses to be used in phase 3 for a new drug intended to treat neuropathic pain. Based on a biomarker measured in phase 1 they have determined a dose which is minimally effective (the lowest dose to show an effect on the biomarker). However, they don’t know how predictive the biomarker will be for the clinical outcome of pain relief.

Which dose(s) should be used?

Answer 4

A range of doses between the minimally effective and the maximum tolerated

The aim is to define the dose-response and/or the concentration-response relationships. This will usually involve at least 3 doses - ideally at least one dose on each of the lower shallow part of the curve, the steep part of the curve and the upper shallow part of the curve. Of course, all doses tested also must be at or below the maximum tolerated.