Project design
Next to choosing the subject for study, time
spent carefully designing a project is never wasted. There are many different
types of scientific study. The design used depends totally on the study. Beloved
of present scientists, the randomised controlled trial is regarded as the best
method of scientific research. It must not be forgotten that much surgical
practice has been advanced by other different types of study such as those
listed in Table 72.2. For example, testing a new type of operation often
requires a pilot study to assess feasibility followed by a formal randomised
controlled trial.
Research
can be qualitative or quantitative. Quantitative research uses hard data to
speak for themselves. A medical condition is analysed systematically using hard
objective endpoints such as death or amputation. In qualitative research data
often come from patient narratives, and the psychosocial impact of the disease
and its treatment are analysed, for example narratives of breast cancer. This
sort of data is often collected using quality of life measurements. A variety of
different quality of life questionnaires exists to suit several different
clinical situations. Much of the best research is both quantitative and
qualitative.
As
finances for healthcare are always stretched, it is also important to include a
cost—benefit analysis in any major area of research so that the value of the
proposed intervention or change in treatment can be assessed.
Sample size
Calculating the number of patients required to
perform a satisfactory investigation is a very important prerequisite to the
study. An incorrect sample size is probably the most frequent reason for
research to be invalid. So often surgical trials are marred by the possibility
of error caused by the inadequate number of patients investigated.
•
Type I error — benefit is perceived when really there is none (false
positive).
•
Type II error — benefit is missed because study has small numbers
(false negative).
Calculating
the number of patients required in the study can overcome this bias.
Unfortunately, it very often reveals that a larger number of patients is needed
for the study than can possibly be obtained from available resources. This often
means expanding enrolment by using a multicentric study. There is no point in
embarking on a trial when it will never be possible to recruit an adequate
sample size. Never forget that more patients will need to be randomised than the
final sample size to take into account patients who die, drop out or are lost to
follow-up.
The
following is an example calculation for a study to recruit patients into two
groups. In order to calculate a sample size it is common practice to set the
level of power for the study at 80 per cent with a 5
per cent significance level. This means that if there is a difference
between study groups, there is an 80 per cent chance of detecting it. Based on
previous studies, realistic expectations of differences between groups should
be used to calculate sample size. The formula below uses the figures of a
reduction in event rate from 30 to 10 per cent (e.g. new treatment expected to
reduce complication rate such as wound infection from 30 to 10 per cent):
8x
r(100—r)+s(100—s)
(r~s)2
8x
30(100—30)
+ 10(100—10) = 60 needed in each group
Eliminating
bias
It is important to imagine how a study could
be invalidated by thinking of things that could go wrong. One way to eliminate
any bias inherent in the data collection is to have observers or recorders who
do not know which treatment has been used (single blind). In the best randomised
studies neither patient nor researcher is aware of which therapy has been used
until after the study has finished (double blind). Randomised trials are
essential for testing new drugs. In practice, however, in some surgical trials
randomisation may not be possible or ethical.
Study protocol
Now that the question to pose has been decided
and it has been checked that sufficient patients will be available to enroll into
the study, it is time to prepare the detail of the trial. At this stage a study
protocol should be constructed to define the research strategy. It should
contain a paragraph on the background of the proposed study, the aim and
objectives, a clear methodology, definitions of population and sample sizes, and
methods of proposed analysis. It should include the patient numbers, inclusion
and exclusion criteria, and the time scale for the work. At this stage it is
helpful to construct a flow diagram giving a clear summary of the research
protocol
and its requirements (Fig. 72.1). It is helpful to imagine the paper that will
be written about the study, before it is performed. This may prevent errors of
data collection.
When
a study is planned, sufficient time should be reserved at the beginning for
fund-raising and obtaining ethical approval if required, and afterwards for
collecting the data and writing it up. A data collection form should be designed
or a computer collection package developed. Do not forget that if data are
collected on computer, appropriate safeguards for privacy and confidentiality
will be necessary. It is important to ensure the co-operation of any other
specialities or clinicians who will be involved in the study and to agree on the
sharing of responsibility for the trial. This will also help to prevent
disagreement about who takes the credit once a study is ready for presentation
and publication.
Ethics
Common sense is the best guide to whether a
study is ethical or not. If there is any doubt consult a local ethics committee,
available in all hospitals. Whenever a patient has treatment chosen by chance,
ethical approval is required. All multicentric trials need approval. Even for
nonrandomised trials it is important to try and obtain written consent for any new or extraordinary procedure or therapy.
All studies involving animals require approval from statutory licensing
authorities.
Leave
plenty of time for this to be obtained and do not embark on the study until
approval has been granted. Ethics committees prefer to see fully developed trial
protocols but it is often possible to get some preliminary advice from the
committee chairman. Ethics committee forms are often long and detailed, and it
is important that these are filled in correctly. All dealings with ethics
committees should be intelligent and courteous.
Most
ethics committees are briefed to ensure that a project does not incur hidden
expenses to a hospital. The cost of nonroutine investigations and extra
treatments should be covered by a grant application, or at least underwritten by
a hospital finance department.