Search this site
MRCP Part II: Written
User login
Drug trials
Drug trials may be
Trial design  Arrangement  Notes 
Doubleblind 


Singleblind 


Unblind / Open 


Crossover studies 


Parallel studies 

Intention to treat analysis
 Individuals are analysed according to the group they were randomised to regardless of whether they complied or completed the study or not
Basic Statistics
Averages:
 Mean: The arithmetic mean is the average value
 Mode: The most frequent value
 Median: The middle value when all the values are ranked. It is a more robust measure of the centre of a distribution as it is not affected by outliers as the mean
Standard deviation
 Measure of spread or variability of a set of measurements
 The smaller the SD or variance, the more tightly grouped the values
Standard error
 Measure of how precisely the sample mean approximates the population mean
 Can be used to construct confidence intervals
Confidence Interval
 Range of values within which the "true" population parameter is believed to be found, within a given level of confidence
Sensitivity
 A measure of how good a test is in detecting those individuals that have the disease
Specificity
 A measure of how good a test is in detecting those individuals that do not have the condition
Null hypothesis
 States that there is no difference between groups#
 Significance tests are carried out on the assumption that the null hypothesis is correct
 If Pvalues are large (>0.05), then there is insufficient evidence to reject the null hypothesis
 Statistical significance implies that the associations are unlikely to be due to chance and hence the null hypothesis can be rejected
Type I error (false positive)
 Probability of failing to accept the null hypothesis when it is correct
 The probability of making a type I error (alpha) is the level of statistical significance
Type II error (false negative)
 Probability of failing to reject the null hypothesis when it is false
 The probability of making a type 2 error (B) is determined by the power of the study (1B)
 If B is set at 10%, then there is 10% hance of failing to reject a false null hypothesis
 Most studies have a power of 8090%
 The power of a study is particularly increased by increasing the sample size
Drug studies
Preclinical: form the basis of the first in man studies
 Invitro pharmacokinetic (PK) and pharmacodynamic (PD) studies
 Animal PK, PD
 Toxicity
Clinical trials: Phase I  safety assessment studies
 Gradually increasing the dose based on the PK until the desired effect or adverse effects are observed
 Performed on healthy volunteers
 Data help to define the candidate dosage forms and regimens for evaluation in phase 2 in small numbers of patients
 Placebo controlled and usually double blind
Clinical trials: Phase II  defining likely safe and efficacious dose for the large phase 3 trials
 Dosage selection
 Dosage range
 Effects on patient variables  ie in patients with the target disease
 Dose response trials
 Efficacy
Clinical trials: Phase III  large scale trials comparing the new treatments to existing treatments
 Population PK/PD studies  this can also improve computer modelling
 Large efficacy trials
 PK/PD in special populations
 Once complete, the drug is usually submitted to the regulatory authorities for a product licence
Clinical trials: Phase IV  post marketing surveillance
 Allows for further refining of the drugplacebotherapeutic profile
 Greater assessment of efficiacy and toxicity