Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Figure 2. Mean pharmacokinetic profiles for the repeated example bioequivalence study.1.2 –- -- - Test drug—— Reference drug1.0 –Plasma concentration (mmol/L)0.8 –0.6 –0.4 –0.2 –0 –|Predose|5|10|15|20|25Time after dosage (hours)The same might happen if blood samples for pharmacokinetic analysis are nothandled properly. For example, consider an anonymized study where twoformulations of a drug are compared to see if they are bioequivalent. Bothformulations are chemically unstable and break down very rapidly, hence certainchemicals need to be added to the blood samples as stabilizers. Thepharmacokinetic analysis showed that the test formulation was significantly lessbioavailable than the reference drug (see Figure 1). However, the study debriefshowed that the test-drug blood samples had a lower concentration of stabilizer;this caused the test drug to break down more quickly than the reference drug andshow falsely lower concentrations when assayed. When the study was repeatedusing the same drugs with adequately stabilized blood samples, the meanconcentrations of the two drugs were very similar (Figure 2).In order to avoid this type of bias, trials should be conducted according tostandardized written protocols with clearly defined study procedures. Studypersonnel must be well trained and certified for particular tasks to ensure thatthe various measurements and assessments are performed identically on everysubject and on each occasion. Study participants should be closely supervisedwherever possible to ensure their compliance and to check that study restrictionsare observed.59