Definition: “A clinical trial is a planned experiment on
human beings which is designed to evaluate the effectiveness of one,
or more, forms of treatment.”
(Altman, 1991)
“An experiment is a series of observations made under conditions
controlled, or arranged, by the investigator.”
(Piantadosi, 1997)
Treatment: a drug (pharmaceutical) or other form of medical treatment (e.g. surgery, radiotherapy, diet, counselling); method of organising and or delivering health care (e.g. pro-active call-centre based treatment support (PACCTS), education leaflet, phone app).
Classification: is by purpose or by phase in drug development.
Phase I: focus upon the Pharmacokinetics/Pharmacodynamics (absorption, distribution, metabolism and excretion of a drug or vaccine) and toxicity (drug safety); Maximum Tolerated Dose (MTD).
Phase II: initial clinical investigation into doses and dose schedules (dose-finding) and early indication of efficacy.
Phase III: aimed at full scale evaluation, efficacy, of a new, experimental, treatment compared to a standard therapy or placebo, acting as a control.
Phase IV: measure effectiveness, post marketing surveillance (information regarding uncommon side-effects, long-term effects).
Effect: - “difference between what happened to the patient as a result of treatment and what would have happened if treatment had been denied”, (Senn, 1997).
Efficacy: - “the true biological effect of a treatment” (Piantadosi, 1997, p 521) and relates to the question: Does the treatment work under idealised (e.g. study) conditions?
Effectiveness: - “the effect of a treatment when widely used in general practice” (Piantadosi, 1997, p 521) and relates to the the question: Does the treatment work in practice (i.e. in the real world)?
Efficiency: - the economics of treatment (time and cost related).
The research protocol is a formal written document specifying the research plan for a clinical trial. It is the single most important quality control tool:
is necessary when applying for a grant to carry out a trial
is required for local ethics committee review
provides sufficient detail to serve developmental, ethical and peer review purposes
guidelines: “Good Clinical Practice” (GCP), ICH E6
publication is encouraged:
http://controlled-trials.com/mrc
http://thelancet.com
background and clear statement of study aims
information on patient selection (in/ex-clusion)
details of treatment schedules
methods of evaluation of patients response to treatment
the general trial design
the recruitment and methods of randomisation of patients
how patient consent was acquired
the required study size
details of the planned monitoring of trial progress
explicit details of the forms and data handling
the intended handling of protocol deviations
plans for the statistical analysis
details of administrative responsibilities
(Pocock, 1983, P28-31)
Guidelines exist for promoting Good Clinical Practice, particularly for assessing safety and efficacy of medicinal products:
Committee for Proprietary Medicinal Products (CPMP)
International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH). Adopted on 1st May 1996 by European Union, the United States and Japan
ICH E6: Guideline for Good Clinical Practice
ICH E9: Statistical Principles for Clinical Trials
http://www.ich.org
Food and Drug Administration (FDA): US Dept. of Health and Human Services Agency
http://www.fda.gov
Guidelines also available from International Federation of Pharmaceutical Manufacturers Associations
http://www.ifpma.org