2. Case study and case series

KNOWLEDGE FOR THE BENEFIT OF HUMANITYKNOWLEDGE FOR THE BENEFIT OF HUMANITY

PUBLIC HEALTH AND EPIDEMIOLOGY (HFS3063) Epidemiological Study Designs:

CASE STUDY, CASE SERIES

Dr. Dr. MohdMohd RazifRazif ShahrilShahril

School of Nutrition & Dietetics School of Nutrition & Dietetics

Faculty of Health SciencesFaculty of Health Sciences

UniversitiUniversiti Sultan Sultan ZainalZainal AbidinAbidin

1

Topic Learning Outcomes

By the end of this lecture, students should be able to;

• describe case study and case series study design.

• explain the advantages and disadvantages of case study and case series design.

• differentiate case series with cohort study design

2

Case study • Detailed presentation of a single case or handful of

cases

• Generally report a new or unique finding e.g.:

– previous undescribed disease

– unexpected link between diseases

– unexpected new therapeutic effect

– adverse events

• The case may be an individual, an event, a policy, etc

3

4

Case reports in the larger scheme of things

Case studies and reports are low on the totem pole

• Preliminary observations are frequently later

refuted

• May rationalize questionable treatments

– e.g., glycemic index diet vs. carbs counting among

gestational diabetes patient

• Biased reporting

– Negative studies may not be published

• Not experimental

5

When the gold standard loses its luster

• RCTs are hard and expensive to carry out!

• Difficult to design an effective placebo

• Treatment by nature involves multiple components

• Difficulty blinding participants

– e.g., manipulation vs. massage

• Everyone knows if they receive placebo

– Randomization flaws

• Recruiting patients from advertisements

– Non-equivalent groups

• Ethics involved in giving patients a placebo

6

Enter the lowly case report

• Not a clinical study per se, but high in clinical relevance

• Well-done case reports may offer more than lousy clinical trials – In judging a prize fight, how to compare 300 light

punches with 200 direct hits?

• May lead to clinical studies

• In rare or new pathologies, may be first evidence – e.g., Thalidomide and birth defects, toxic shock

syndrome, Lyme disease

• 20-30% of medical articles involve < 10 patients

7

Research value of case report

• Illustrate or support a hypothesis

– Atlas subluxation in a man with gastritis

• Prompt a new hypothesis

– Atlas subluxation can cause gastritis

• Report treatment failures

– Correcting atlas did not relieve gastritis

• Report iatrogenic reactions

– Gastritis better, but pt. developed brain tumor!

8

A case report is…

• “Biomedical story-telling” (Lawrence, 1991)

• A delivery vehicle for clinical education; indeed,

“the case must have educational value”

(Lawrence, 1991)

• A stimulant for more comprehensive and

prospective research

9

A case report is not…

• An anecdote

– Def. - unpublished narrative

• A testimonial

• An advertisement

• “Persuasive communication” (Keating)

10

Selecting a case

• Case should illustrate an important point

regarding case management (i.e., examination,

evaluation, intervention, outcome).

• Case does not have to have a positive outcome

• Case does not have to be unusual or unique

11

Sample case reports classified • Spinal manipulative treatment for 12 pregnant LBP

patients [Clinical Education]

• Brucellosis: a rare cause of the unstable spine [clever

chap]

• RA: a case report [novel treatment]

• Grand Rounds discussion: patient with acute LBP

[Grand Rounds]

• Rotary manipulation for cervical radiculopathy

[unexpected association]

12

cont. Sample case reports classified

• Mixed sacral fracture before chiropractic adjustment

[unexpected outcome]

• Membranous glomerulonephropathy associated with MS

[unexpected occurrence]

• Post-myelographic cauda equina in young acromegalic

[unique case]

• Arthritis and acetyl myristoleate [glorified advertisement]

• Autism and chronic otitis media [anecdotal]

13

Case series • Experience of a group of patients with a similar

diagnosis

• Assesses prevalent disease

• Cases may be identified from a single or multiple

sources

• Generally report on new/unique condition

• A realistic design for rare disorders

14

(cont.) Case series • Variation on the theme of the solitary case report

• Retrospective look at series of cases that have features

in common

• Common diagnosis, treatment, measures

– In the literature already

• Each case may be separately described, or the cases

may be lumped together with data summaries

15

(cont.) Case series Advantages

• Useful for hypothesis generation

• Informative for very rare disease with few established

risk factors

• Characterizes averages for disorder

Disadvantages

• Cannot study cause and effect relationships

• Cannot assess disease frequency

16

Cohort study vs. case series

17

COHORT STUDY CASE SERIES

• Patients are sampled on the basis of exposure.

• Information about baseline characteristics is obtained, and the occurrence of outcomes is assessed during a specified follow-up period.

• At baseline, all exposed or unexposed persons or both may be included.

• Exposure can be a risk factor (such as smoking), a disease (such as diabetes mellitus), or an intervention (such as hip replacement).

• In principle, a cohort study enables calculation of an absolute risk (or rate) for the outcome, given a particular exposure. If a comparison group is included, a relative risk can also be calculated.

Patients with a particular disease or disease-related outcome are sampled. Case series exist in 2 types: 1. Sampling is based on a specific outcome and

presence of a specific exposure. Cases are selected on the basis of a striking association between exposure and outcome. This type of case series can be formally thought of as describing 1 cell (the exposed cases) in an epidemiologic 2 x 2 table.

2. Selection is based only on a specific outcome, and data are collected on previous exposures. Cases are reported regardless of whether they have specific exposures. This type of case series can be seen as the case group from a case–control study or as 2 cells (the exposed and unexposed cases) from an epidemiologic 2 x 2 table.

The risk for the outcome, given the exposure, cannot be calculated from either type of case series.

Source: Dekkers et al. (2012)

18

Test: Case series or cohort study?

SCENARIO 1 • A surgeon performs a new procedure for a life-

threatening condition on 20 patients. Ten patients survive. Two possible papers can be considered:

• 1A. A description of all treated patients and follow-up, with calculation of mortality risk. No comparison group is included.

• 1B. The same as 1A, except that the treated group is compared with a historical group from the same institution to compare mortality risk.

19

Test: Case series or cohort study?

SCENARIO 1 • A surgeon performs a new procedure for a life-

threatening condition on 20 patients. Ten patients survive. Two possible papers can be considered:

• 1A. A description of all treated patients and follow-up, with calculation of mortality risk. No comparison group is included (COHORT STUDY)

• 1B. The same as 1A, except that the treated group is compared with a historical group from the same institution to compare mortality risk (COHORT STUDY)

20

Test: Case series or cohort study? SCENARIO 2 • Data were collected on patients who had bone marrow

depression at 1 hospital. Potential risk factors, including drugs known to induce bone marrow depression, were assessed for all patients. The investigators assessed whether bone marrow depression was still present after 1 year among patients who received 1 of 2 drugs used to treat the same disease. Two papers can be written on the basis of these data:

• 2A. A description of all patients with bone marrow depression and the frequency of potential risk factors for bone marrow depression

• 2B. A comparison of the risk for persistent bone marrow depression after 1 year, for either drug, with calculation of the absolute and relative risks for persistence

21

Test: Case series or cohort study? SCENARIO 2 • Data were collected on patients who had bone marrow

depression at 1 hospital. Potential risk factors, including drugs known to induce bone marrow depression, were assessed for all patients. The investigators assessed whether bone marrow depression was still present after 1 year among patients who received 1 of 2 drugs used to treat the same disease. Two papers can be written on the basis of these data:

• 2A. A description of all patients with bone marrow depression and the frequency of potential risk factors for bone marrow depression (CASE SERIES)

• 2B. A comparison of the risk for persistent bone marrow depression after 1 year, for either drug, with calculation of the absolute and relative risks for persistence (COHORT STUDY)

22

Test: Case series or cohort study?

SCENARIO 3 • In 1 hospital, a subset of patients hospitalized

with Escherichia coli–induced hemolytic–uremic syndrome (HUS) developed neurologic symptoms during their stay. Demographic and clinical characteristics of patients with HUS were collected. Two papers can be considered:

• 3A. A description of only patients who had HUS and neurologic symptoms

• 3B. A comparison to assess whether the risk for neurologic symptoms was higher in male than in female patients with HUS

23

Test: Case series or cohort study?

SCENARIO 3 • In 1 hospital, a subset of patients hospitalized

with Escherichia coli–induced hemolytic–uremic syndrome (HUS) developed neurologic symptoms during their stay. Demographic and clinical characteristics of patients with HUS were collected. Two papers can be considered:

• 3A. A description of only patients who had HUS and neurologic symptoms (CASE SERIES)

• 3B. A comparison to assess whether the risk for neurologic symptoms was higher in male than in female patients with HUS (COHORT STUDY)

24

Thank YouThank You

25