Question

Discuss in detail the testing of pharmaceutical drugs and also please use examples.

Answer 1

After testing of the drug on animals, the results are observed to determine its efficacy and toxicity, these are known as pre-clinical trials, which are followed by clinical trials if results are promising.

The clinical trials are carried out in three phases.

1). Phase I

2). Phase II

3). Phase III

Phase I clinical trials: These studies are mainly targeted to assess the safety of the drug in patients (means, the test subjects are small number of patients suffering from any type of cancer). The following are findings of phase I clinical trials.

a). The dose at which the drug can be used safely

b). Side effects at different dose levels

c). Therapeutic response

It takes long time to complete phase I clinical trials because it is carried out in small number of people. The first group (cohort group) receive a small dose of the drug. Depending upon the results, the dose will be gradually increased with each study group. At each stage, the side effects and therapeutic response is observed to determine the best effective dose, this is known as dose escalation study.

Phase II clinical trials: The efficacy and safety of the test drug is tested in about 300 individuals

Phase III clinical trials are performed on about 1000 to 2000 number of patients of specific diseases to evaluate the efficacy and safety of the new therapeutic approaches. This includes the randomized controlled trains in multiple centers.

This is also known as “pre-marketing studies” because they are conducted to study the patient’s response before marketing the drug.

Example: Shire biopharmaceutical companies’ product Xiidra (lifitegrast ophthalmic solution 5%, twice a day) was approved by FDA for the treatment of signs and symptoms of dry eye disease. It is the first prescription drug approved for dry disease. The effect of Xiidra was assessed by four placebo-controlled clinical trials on the disease signs and symptoms at baseline, two weeks, six weeks and twelve weeks. About 2500 number of patients were included in this study, they were administered with either Xiidra or placebo twice daily for 12 weeks. All the four studies showed a significant reduction in signs and symptoms measured in terms of eye dryness score at six weeks and twelve weeks. Three of the four studies showed a significant reduction in inferior corneal staining score at twelve weeks treatment with Xiidra. The most typical side effects associated with Xiidra include irritation at the site if the application, diminished visual activity and unusual taste sensation. The side effects are reported in about 5% to 25% of the population.