Question 29.1

A Phase III study of a drug was undertaken to determine if it improved mortality in severe sepsis. The study design was a randomized, double-blind, placebo-controlled, multicenter trial (n=1200). The mortality rates in the placebo arm and the trial drug arm were 32% and 26% respectively. There were no adverse effects noted in relation to the trial drug.

a) What do you understand by the term Phase III.?

b) What was the absolute risk reduction?

c) What was the relative risk reduction?

d) Calculate the “number needed to treat”?

a) What do you understand by the term Phase III.?

Phase III trials compare new treatments with the best currently available treatment (the

standard treatment). Much larger sample sizes than Phase II and are usually randomised. They are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment.

b) What was the absolute risk reduction?

6%

c) What was the relative risk reduction?

18.75%

d) Calculate the “number needed to treat”?

16.66

Again, the candidate is called upon to recall equations and to perform basic mathematics. A helpful list of such equations is available.

a) a Phase III trial is a study of the treatment effect of the drug, which is performed in a large group of patients, all of whom have the disease being studied. The purpose of a a Phase III trial is to test efficacy of an experimental treatment in comparison to standard of care or "gold standard" therapy.

One can find more information about the phases of clinical research in brief in this 2011 BMJ statistics question by Phillip Sedgwick, in greater detail in this article by M.A. Rogers, and in great detail in this 2013 publication from the IJPCBS.

b) Absolute risk reduction (ARR) = (AR in treatment group - AR in control group)

In this trial, the ARR = (32% - 26%) = 6%

c) The relative risk reduction (RRR) = (ARR / control group AR)

In this trial, RRR = (0.06 / 0.32) = 18.75%

d) The Numbers Needed to Treat (NNT) = (1/ARR),

In this trial, NNT = (1 / 0.06) = 16.6

Sedgwick, Philip. "Phases of clinical trials." *BMJ* 343 (2011).

Rogers, M. A. "What are the phases of intervention research." *Access Academics and Research* (2009).

Rohilla, Ankur, D. Sharma, and R. Keshari. "Phases of clinical trials: a review."*IJPCBS* 3 (2013): 700-3.