Case report and case series
Objectives
By the end of this chapter you should:
• Understand the importance of case reports and case series as providing evidence for clinical decision-
making.
• Be able to identify and critically appraise case reports and case series.
• Be able to conduct your own case report or case series.
• Be able to list the advantages and disadvantages of case reports and case series.
BACKGROUND
According to NHS Centre for Reviews and Dissemina-
tion, case reports and case series are near the bottom
of the hierarchy (Fig. 1.5) of what counts as reliable evi-
dence for clinical decision-making.
• A case report (or case study) usually describes a sin-
gle unique case or finding of interest.
• A case series (or clinical series):
• is a descriptive study that reports on data from a
group of individuals who have a similar disease
or condition.
• is a type of observational study useful for identi-
fying similar or differing characteristics between
selected cases.
• can be prospective or retrospective and usually
involves only a small number of individuals.
• can include either non-consecutive (a selection
of cases) or consecutive individuals (all cases)
with the same condition or disease.
• The information gained from a case series can be
used to generate hypotheses.
• Case series studies are commonly used to report on a
consecutive series of patients with a defined disease
who have been treated in a similar manner (without
a control group).
COMMUNICATION
The role of case reports and case series
Most case reports and case series cover one of six
topics:
1. Identifying and describing new diseases.
2. Identifying rare or unique manifestations of known
diseases.
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3. Audit, quality improvement and medical education.
4. Understanding the pathogenesis of a disease.
5. Detecting new drug side effects, both beneficial and
adverse.
6. Reporting unique therapeutic approaches.
CONDUCTING A CASE REPORT
Preparation
• Identify an interesting case in a clinic or on the ward,
with guidance and advice from a senior colleague.
• Having identified a suitable case, carry out a litera-
ture review to explore the uniqueness of the case.
Have similar cases already been published?
• Discuss the case with senior doctors who have been
looking after the patient in order to gain permission
and support.
• Gain written consent from the patient, especially
if there may be patient identifiers in the report,
including medical pictures and specific clinical
details.
• Some journals require patient consent regardless of
whether or not patient identifiers are included in the
report, so read the journal guidelines carefully!
• Having successfully completed the above, relevant
information should be gathered about the case from
the patient notes, available imaging, laboratory
results and other relevant sources.
Structuring a medical case report
The following guideline for writing a case report manu-
script can also be used as a checklist when critically
appraising case studies already published.
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 Case report and case series
Abstract
• There is usually a strict word limit for the abstract, so
carefully read the journal guidelines before you begin!
• The abstract will help readers discern whether they
are interested (or not interested) in reading the case
report.
• The abstract should include all the sections included
in the main text of the case report, including the
introduction and objective(s), case presentation,
discussion and conclusion.
• The abstract should be engaging and to the point,
highlighting the key details from the main text of
the case report.
Introduction
• The opening sentence should be catchy and attract
the attention of the reader.
• The subject matter of interest should be introduced
with background information on the topic.
• The search strategy for the literature review, includ-
ing the search terms used, should be described with
enough detail to allow the reader to easily reproduce
the search.
• The purpose and merit of the case report should be
highlighted using the literature identified in the search.
• The patient case should be introduced to the reader
with a one- or two-sentence description.
• There should not be more than three or four concise
paragraphs for the introduction of the case report.
Case presentation
• The case should be described in enough detail to
allow readers to make their own conclusions about
the case.
• Patient identifiers such as precise dates and the
patient’s date of birth should be avoided.
• A narrative description of the case should be written
with significant events discussed in chronological
order (headings for each part of the patient history
should not be used).
• The patient information described should be rele-
vant and may include details on:
• Patient demographics – age, sex, race, height and
weight.
• Presenting complaint.
• Past medical history.
• Drug history before and during the admission
(include over-the-counter medications, recrea-
tional drugs, vaccines and herbal remedies) –
the name, dose, route, times of administration
and compliance rates of all medications should
be listed.
• Renal and hepatic function – allows assessment of
the appropriateness of the medication doses used.
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• Drug allergies – including the name of culprit
medications, the date and type of drug reactions.
• Family history.
• Social history – diet, occupation, smoking and
alcohol status.
• Important physical examination findings.
• Relevant (not routine) laboratory data.
• Differential diagnoses and the diagnostic
procedure.
• Report the results of any diagnostic tests.
• Therapeutic effects and side effects of any treat-
ments on the disease outcome.
• Potential causal relationships between an expo-
sure and outcome.
• Current status of the patient case and future treat-
ment plans.
• Relevant figures should be used, including electro-
cardiograms (ECGs), radiological images, blood
films and photographs of skin manifestations.
Discussion
• What new information has been learnt from the case
report?
• Comment on how unique the case is by comparing
and contrasting it to other cases already published in
the literature.
• Are there any inaccuracies in the data that would
question the validity of the case report?
• What are the limitations of the case report?
• Summarise the key points raised from the case report.
Conclusion
• A justified, sound and brief conclusion should be
written based on information reviewed as part of
the discussion.
• Any recommendations should be evidence-based
rather than based on speculation.
• Describe whether any new findings from the case
will have an impact on clinical practice.
• Has the case report generated any novel hypotheses
that could be investigated using a study higher up in
the hierarchy of evidence?
References
• Whether other articles are quoted or paraphrased, it
is essential that all sources of information referred to
in the case report are acknowledged in the reference
section at the end of the paper.
• The Harvard Referencing System is a collection of
rules that standardises the format in which articles
are referenced (please refer to Chapter 5 for an in-
depth discussion on how to reference articles using
the Harvard Referencing System).
• Citations should be included in parentheses in the
main text of the case report.

CONDUCTING A CASE SERIES
Guidelines similar to those outlined for case reports
should be followed when conducting a case series.
However, specifically for case series, it is important to
consider the following:
• Is the case series prospective or retrospective? Pro-
spective case series are less prone to bias.
• Case series should be carried out according to a pre-
defined protocol, which clearly defines all stages of
the study, including patient selection, measures,
data collection, analysis and reporting.
• Inclusion and exclusion criteria should be clearly
defined, with all eligible patients selected in order
to avoid selection bias.
• Are non-consecutive or consecutive cases selected?
Recruiting consecutive cases is preferable in order
to avoid selection bias.
• Are patients recruited over a fixed time period or
(preferably) until a sufficient number of cases are
identified? Formal sample size calculations could
be used if a particular change in measure is worth
demonstrating.
• The diagnostic process should be clearly documen-
ted for all patients.
• Details of baseline information, and pre- and post-
treatment measures should be recorded.
• The outcome for all study participants should be
measured in the same way according to the prede-
fined protocol.
• Outcomes should be measured objectively, wherever
possible, in order to minimise measurement bias.
• Measurements made should be valid and reliable.
• Differences in treatment effects should be compared
and contrasted between cases.
• Quantitative data should be statistically analysed, for
example, by calculating the average value (the mean)
and the degree of spread of the data set (e.g. the stan-
dard deviation or interquartile range).
• The ‘flow of patients’ should be described, account-
ing for anyone who dropped out of the study, there-
fore avoiding selection bias (please refer to
Chapter 7 for a discussion on selection bias).
• An intention-to-treat analysis should be considered,
where appropriate (please refer to Chapter 6 for a
discussion on how to calculate and interpret the
intention-to-treat analysis).
CRITICAL APPRAISAL OF
A CASE SERIES
Key methodological issues should be considered when
critically appraising a case series:
Key examples of case reports 11
1. Was there a well-defined study protocol with a clear
objective or research question?
2. Were consecutive cases within a specified time inter-
val enrolled?
If non-consecutive cases were enrolled, the study results are
subject to selection bias.
3. Were explicit inclusion and exclusion criteria stated
for the selection of study participants?
If the study population was too restrictive, the generalisability
of the results to more representative populations will be
limited.
4. Were relevant exposure variables measured accu-
rately?
5. Were potential confounding factors measured?
If confounding factors were not taken into account, a poten-
tial relationship between the exposure and outcome may be
biased.
6. Were the outcome measures clinically relevant and
measured accurately?
7. Was outcome measure data collected prospectively?
Prospective data collection will improve the accuracy of the
data collected.
8. Was there a high loss to follow-up?
The study findings are less valid if a considerable number of
participants dropped out of the study (loss-to-follow-up bias).
ADVANTAGES
AND DISADVANTAGES
What are the advantages and disadvantages of case
reports and case series? Figure 11.1 highlights the key
points that apply to case reports, case series or both
types of papers.
KEY EXAMPLES OF CASE
REPORTS
The first cardiac transplantation
In 1967, Christiaan Barnard, a surgeon from South
Africa, published a case report on the first human heart
transplant. While the transplant operation was only
temporarily successful, this was an important historical
event. Within one year of this publication, surgeons
from the Texas Heart Institute had performed 20 heart
transplant operations. The first human heart transplan-
tation and subsequent research at the Univeristy of Cape
Town (and in other specialist surgical centres) over the
following 15 years laid the foundation for heart trans-
plantation to become a well-established surgical option
for end-stage cardiac disease.
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 Case report and case series
Figure 11.1 Advantages and disadvantages of case reports and case series
Advantages
Case Reports and Case Series
• Useful for describing clinical experience, including
identifying new diseases and reporting unique thera-
peutic approaches to known diseases.
• Relatively easy and inexpensive to conduct.
• Information gained can help provide suggestions for
generating clinical hypotheses, which can be tested
using stronger study designs.
• Allows junior doctors and students to apply new
knowledge and skills.
Case Reports
• Many different aspects of the patient’s medical situa-
tion, including patient history, physical examination,
diagnosis, social issues and follow-up can be detailed.
• Relatively quick to complete.
Multiple myeloma
Multiple myeloma is a disorder of plasma cell prolifer-
ation in the bone marrow that is associated with skeletal
destruction. The first well-known case of multiple mye-
loma was described by Dr William MacIntyre, who pub-
lished a case report on the features of multiple myeloma
proteinuria based on a urine sample produced by
Thomas Alexander McBean, a 45-year-old grocer from
London. These urine specimens were subsequently
studied in detail by Henry Bence Jones, a chemical
pathologist from London, who identified the protein
as a ‘hydrated deutoxide of albumin’ and commented
on its importance in diagnosing multiple myeloma.
These findings accredited him with the discovery of
Bence Jones protein in the urine!
KEY EXAMPLE OF A CASE SERIES
Thalidomide and congenital
abnormalities
Thalidomide, a sedative drug first synthesised in 1953,
was widely prescribed for the morning sickness often
experienced by pregnant women. By 1958, thalidomide
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Disadvantages
Case Reports and Case Series
• At the bottom of the hierarchy of evidence due to the
lack of scientific rigour (compared to larger observa-
tional and experimental study designs).
• Cannot usually be used to establish cause-and-effect
relationships.
• If the case(s) chosen are not representative of the wider
population, the findings may not be generalisable.
Case Series
• Prone to selection, measurement and attrition bias.
was being promoted as an anti-emetic in many countries
around the world. However, in 1961, William McBride,
an obstetrician from New South Wales, published a
famous case series to alert healthcare professionals of
the dangers of thalidomide:
Congenital abnormalities are present in approxi-
mately 1.5% of babies. In recent months I have
observed that the incidence of multiple severe
abnormalities in babies delivered of women
who were given the drug thalidomide (‘Distaval’)
during pregnancy, as an anti-emetic or as a seda-
tive, to be almost 20%.
These abnormalities are present in structures
developed from mesenchyme – i.e., the bones
and musculature of the gut. Bony development
seems to be affected in a very striking manner,
resulting in polydactyly, syndactyly, and failure
of development of long bones (abnormally short
femora and radii).
Have any of your readers seen similar abnormal-
ities in babies delivered of women who have taken
this drug during pregnancy?
Following this publication, the drug was eventually
withdrawn and countless babies were saved from the
teratogenic effects of thalidomide.