Clinical Trials

Randomised controlled trials (RCTs) allow data on the safety and efficacy of health interventions
(e.g., drugs, diagnostics, devices, therapy protocols) to be collected. Trials can be conducted
using healthy volunteers or patients, depending on what the trial is investigating and its stage of
development. Trials are usually one of four phases (Phase I to Phase IV):
Phase I tests an experimental drug or treatment in a small group of healthy people for the
first time to evaluate its safety, determine a safe dosage range, and identify side effects. This
phase usually involves less than 100 participants.
Phase II tests the drug or treatment in a small group of people with the condition or disease
to see if it is effective and to further evaluate its safety. This phase usually involves no more
than a few hundred participants.
Phase III is carried out on large groups of people to confirm effectiveness, monitor side
effects, make comparisons with commonly used treatments, and collect information that will
allow the experimental drug or treatment to be used safely. This phase usually involves
several hundred to several thousand participants.
Phase IV is considered the surveillance stage and collects additional information including the
drug’s risks, benefits, and optimal use. This phase will involve the general population.
Clinical Trials (b)
If well designed, RCTs are thought by some to be the ‘gold standard’ of clinical research as they
eliminate bias and spurious causality (a false connection between two factors because of a third
factor, e.g. it could be said that children with larger feet are better at maths – however, the older
the child, the larger their feet and also the more practised at maths they are; or you could conclude
that the more fire trucks it takes to put out a fire, the more damage there is – until you consider
that there are more trucks needed when there are larger fires and so the size of the fire is the
cause of the greater damage, not the number of fire trucks). However RCTs can be very
expensive, can take a long time to recruit adequate numbers of participants and may take a long
time to complete particularly if there is participant follow-up.
Examples of research carried out using this type of design can be seen in the papers:
Effect of a participatory intervention with women’s groups on birth outcomes and maternal
depression in Jharkhand Orissa, India: a cluster-randomised controlled trial by Tripathy et al
(2010).
Complementary foods fortified with micronutrients prevent iron deficiency and anemia in
Vietnamese infants by Phu et al (2010).
Study Designs: Key Points To Remember
There are different types of clinical research designs and the question being
investigated will determine the study design used e.g. a clinical trial is used to test a
new drug, an observational study is used to collect epidemiological data, etc.
The various forms of clinical research allow different types of data to be extracted and
analysed so that different types of questions can be answered.
Cohort studies follow specific groups of people over a period of time to see how
outcomes differ when they receive different treatments and interventions.
Case control studies compare people with a specific outcome to individuals without
that outcome to investigate the exposures that may have caused the outcome.
Cross sectional surveys aim to describe the relationship between a health-related state
and other factors of interest in a specified population at a given time, regardless of what may
have preceded or precipitated the health status found at the time of the study.
Case reports are detailed histories of single cases and allow us to uncover unexpected
effects, new diseases, etc., which can lead to increased knowledge.
Clinical trials allow for collection of data on the safety and efficacy of health interventions.
They are thought by some to be the ‘gold standard’ of clinical research.
Maintaining High Ethical Standards, Data Quality And Uniformity In A
Study (a)
How are high ethical standards, data quality and uniformity in the study ensured?
To ensure high ethical standards, data quality and uniformity, studies use both a
protocol and ‘Standard Operating Procedures’ (SOPs, or a Manual of Operations).
The protocol provides the background and justification for the study and covers
issues such as the design, methodology, statistical considerations and
organisation, study timetable, type of recruits, governance, etc. It must capture every step to
ensure that the study’s result is, firstly, the answer to the research question, and secondly, that
the answer is reliable.
The ICH GCP 1996 guidelines define SOPs as: “detailed written instructions created to achieve
uniformity of performance of a specific function within a study.”
SOPs ensure that a task will be performed the same way each time it is undertaken. They translate
the protocol into practice and allow the protocol to operate accurately and to reliably answer the
research question. SOPs are very beneficial for all types of studies.
SOPs are useful as they:
Identify the person responsible for each task e.g. the investigator recruits the participants.
Describe the study procedures and how they are to be completed e.g. the steps to be
followed if collecting samples.
Help train staff into their role: following the SOPs means that everyone in a given role is
trained in the same way every time.
Help monitor site performance: this allows any deviation from the protocol to be identified and
corrected.
Maintaining High Ethical Standards, Data Quality And Uniformity In A
Study (b)
All research study staff should be trained in and have access to a copy of the SOPs. It is essential
that each staff member follows the study’s SOPs to ensure the protocol is being followed and
therefore the participants’ safety and welfare are protected and that the study data is credible and
robust. SOPs should be reviewed regularly (at least annually) to ensure any listed regulations are
up to date and that, if applicable, outlined procedures are updated e.g. if a change is made to the
data collection system due to a more efficient system being identified through the course of the
study.
SOPs are needed when a variation in how a task is carried out could lead to inconsistent,
inaccurate or misleading data. For example, sample transportation in a multi-centred genetic study
in Africa. Here all the samples need to be stored and transported carefully to avoid analytical
problems with the samples. In each site logistics will differ and so each site needs to write their
SOPs to ensure the integrity of their samples.
Quality assurance procedures and procedures for assuring quality of data handling and processing
should all be guided by SOPs. ICH GCP (1996) defines quality assurance as ‘all those planned and
systematic actions that are established to ensure that the study is performed and the data are
generated, documented (recorded), and reported in compliance with GCP and the applicable
regulatory requirement(s)’. SOPS for these procedures should include plans for data checking
(how much will be checked, by whom, and how); audit trails (detailed log showing which data have
been changed, why it was changed, who changed it and when); and source verification procedures
(how much data will be checked against the source documents e.g. medical records).
Key Points To Remember
Uniformity of study and of quality assurance procedures are ensured by the
implementation and use of standard operating procedures (SOPs).
SOPs identify who is responsible for which task, provide the steps to be followed for
study procedures, help all staff to carry out a particular task in the same way, and help to
monitor site performance.
All research study staff should be trained in and have access to a copy of the SOPs.
SOPs also see to it that the quality of the data handling and processing is maintained.