MM20802 Notes

MM20802: Epidemiology in Clinical Practice Notes 21/22
L1 – Use of Epidemiology in Clinical Practice

Definition of clinical epidemiology [x3]
The application of epidemiologic principles and methods to problems encountered in clinical medicine involving the counting of
clinical events
Functions of epidemiology in clinical practices with examples of medical achievements in history [x3]
• Used to understand the pathogenesis of diseases (e.g., understanding COVID-19 transmission)
• Improve diagnostic accuracy (e.g., investigation of Helicobacter pylori 1995)
• Helps patients to reduce risk factors (e.g., Framingham Heart Study 1948)
• Helps physicians to choose the correct therapeutic approach (e.g., polio vaccine trials)
Clinical issues in practice of medicine [x2]

1. Normality/abnormality
- Limits of normality
- Abnormalities associated with having the disease
2. Diagnosis
- Accuracy of diagnostic tests to find the disease
3. Frequency/occurrence
- Case definition for a disease
- Host, spatial, and temporal distribution of a disease
4. Risk/prevention
- Factors associated with likelihood of contracting disease
5. Prognosis
- Consequences of having a disease
- Factors associated with increased or decreased likelihood of recovering from disease
6. Treatment/control
- Effectiveness of therapeutic strategy
- Reducing risk and rate of spread
- Useful tools for diagnosis, treatment, control, and prevention
7. Cause
- Aetiologic agent and its life cycle, pathogenicity, and virulence
- Factors to determine susceptibility and resistance of individuals to disease
8. Source/transmission
- Source and reservoir mechanism
- Spread and route of infection to the susceptible
9. Cost
- Impact of disease in personal and economic terms
Preventive measures with the use of epidemiology [x1]

• Developing interventions to reduce disease or improve health in the community
• Program evaluation
Types of normal and examples [x2]

(1) Gaussian distribution → 2 standard deviations
(2) Percentile → 95th percentile
(3) Risk factor → studies of precursor or statistical predictors of subsequent clinical events
(4) Diagnostic → sensitivity vs. specificity of test
(5) Therapeutic → range of test results beyond which therapy does more good than harm
(6) Culturally desirable → socially or politically aspired to
Types of epidemiology
Experimental and observational
Differences between epidemiology and medicine

Epidemiology Medicine
Concerned with the population as a whole Concerned with the individual person
Uses information to generate hypotheses between exposure Uses information to make diagnoses
and disease
Tests hypotheses using analytical studies Tests diagnoses by conducting additional diagnostic tests
Recommends community intervention Recommends prescribed medical treatment
Basic properties of the normal distribution curve

• Total area under the curve = 1
• Symmetrical about the mean
• ~68.3% of data lies within 1 standard deviation of the mean
L2 – Abnormality
Criteria used to categorise normal and abnormal with examples [x1]
(1) Being unusual
According to frequency of distribution of statistical definition, normal is defined as those that occur frequently, whereas those
that occur infrequently is defined as abnormal.
Example: neonate normal birth weight = 2.5 – 3.5 kg
(2) Being sick
Clinical departure from normal health
Example: high BMI and obesity that increases risk of cardiovascular diseases or even mortality
(3) Being treatable
Treating the condition would lead to a better outcome
Example: treatment of hypertension may prevent serious complications
Normal in the context of medicine

(1) Based on Boorse’s biostatistical theory (BST)
Total absence of pathological conditions
(2) Based on Catita (2020)
No consensual definition and conception in medical literature
Ways to distinguish normal from abnormal

• Data - How is the biologic phenomena measured?
• Variation - How do they vary?
• Distribution - How are they summarised?
Types of data
a) Nominal
b) Ordinal
c) Interval (continuous/discrete)
Sources of variation
Source of variation Definition
Measurement variation
Instrument The means of making the measurement
Observer The person making the measurement
Biologic variation
Within individuals Changes in a person at different times and situations
Between individuals Biologic differences from person to person
L3 – Screening Test
Calculation of screening test and interpretation | Refer to P1 Answer Script [x12]
Validity Definition Formula
Sensitivity Probability that a diseased individual will be 𝑇𝑃
× 100%
classified as diseased 𝑇𝑃 + 𝐹𝑁
Specificity Probability that a healthy individual will be 𝑇𝑁
× 100%
classified as healthy 𝑇𝑁 + 𝐹𝑃
Positive predictive Probability of disease in a patient with (+) results 𝑇𝑃
value (PPV) 𝑇𝑃 + 𝐹𝑃
𝑃𝑟𝑒𝑣 × 𝑆𝑒𝑛
(𝑃𝑟𝑒𝑣 × 𝑆𝑒𝑛) + (1 − 𝑃𝑟𝑒𝑣)(1 − 𝑆𝑝𝑒)
Negative predictive Probability of not having a disease when the test 𝑇𝑁
value (NPV) result is negative (normal) 𝑇𝑁 + 𝐹𝑁
(1 − 𝑃𝑟𝑒𝑣) × 𝑆𝑝𝑒
[(1 − 𝑃𝑟𝑒𝑣)(𝑆𝑝)] + [𝑃𝑟𝑒𝑣(1 − 𝑆𝑒𝑛)]
Accuracy Ability to differentiate the patient and healthy 𝑇𝑃 + 𝑇𝑁
cases correctly 𝑇𝑜𝑡𝑎𝑙 𝑝𝑒𝑜𝑝𝑙𝑒 𝑖𝑛𝑣𝑜𝑙𝑣𝑒𝑑
Interpretation
1. Sensitivity = 0.72
→ Among people with disease, 72% of them were tested positive through the examination
2. Specificity = 0.95
→ Among people with no disease (healthy), 95% of them were tested negative through the examination
3. PPV = 0.693
→ The likelihood of a patient that was tested positive through the examination to actually have the disease is 0.693
4. NPV = 0.91
→ The likelihood of a patient that was tested negative through the examination to actually be healthy is 0.91
Predictive value of a test

• ↑sensitivity ; ↑NPV = Negative test results rules out disease
• ↑specificity ; ↑PPV = Positive test results indicates disease
• ↓prevalence of disease = ↓PPV
Would you recommend [insert test] as a screening/diagnostic tool? Explain. [x10]

• High sensitivity → recommended as screening tool
• High specificity → recommended as diagnostic/confirmatory tool
Conclusion written based on calculation [x2]

• Highly sensitive test (>75% sensitivity) is useful when the test is negative → screening test
• Highly specific test (>75%) specificity) is useful when the test is positive → diagnostic/confirmatory test
Criteria for starting screening programmes

• Disease with fatal and prolonged morbidity
• Detectable at pre-clinical phase
• Availability of confirmatory/diagnostic test
• Availability of treatment facilities
• Must have effective treatment
Criteria for suitable screening test

✓ Cheap
✓ None or low side effects
✓ High reliability and validity
✓ Convenient
✓ Painless
✓ High yield
✓ Acceptable by the community
Differences between mass screening and diagnostic examinations

No. Mass screening Diagnostic (clinical) examination
1. Used in population studies Performed on individuals presenting for medical consultation
2. Medical indications are absent Medical indications are present
3. Low cost and simple Costly and highly complicated
4. Unreliable diagnosis Reliable diagnosis
5. Results cannot be used to prescribe treatment Results are used to initiate therapy
L4 – Diagnostic Strategy and Clinical Disagreement

Four diagnostic strategies in clinical practice and its explanation (benefits and disadvantages) [x10]
(1) Exhaustion
- Method used by medical students
- All areas are explored in equal depth
- No hypotheses are formed or tested
- Advantage → discover surprising details
- Disadvantage → very inefficient
(2) Hypothetico-deductive
- Most widely used method
- Begins during initial phase of interview where someone comes up with a short list of differential diagnosis
- Continuously developed and refined by:
o Clarification skills in medical interview
o Focused physical examination
- Advantage → allows for continuous assessment and refinement of hypothesis | efficient | accurate
- Disadvantage → may miss atypical presentation | may lead to premature closure
(3) Multiple branching
- Arborization method of the delegate
- Pre-set algorithms for exploring problems
- Includes a series of close-ended ‘yes/no’ queries
- Each answer determines next inquiry
- Advantage → efficient | minimises unnecessary testing | based on probability data
- Disadvantage → severely narrows range of inquiry | population-based | little room for uniqueness
(4) Pattern recognition
- Method of the expert
- Realisation of patients’ presentation conforms known picture
- May be associated with different senses (e.g., visual, olfactory, etc.)
- Advantage → efficient | improves with experience
- Disadvantage → may miss atypical presentation | may lead to premature closure |
Definition of clinical diagnosis [x1]

Process of identifying a disease, condition, or injury from its signs and symptoms
Definition of clinical disagreement [x1]

Discrepancy between two or more clinicians in achieving diagnosis that may happen during history taking, performing physical
examination, or interpreting results of a diagnostic test
Reasons for clinical disagreement

Clinician Patient Facility
Different set of knowledge and skills Language barrier Availability of diagnostic test
Novice vs. expert Secretive Hospital location (district/tertiary)
Use of clinical epidemiology to improve diagnostic accuracy

• Using statistical method in reaching diagnosis
• Estimate initial probability of disease
• Sensitivity and specificity of diagnostic test
• Refined probability based on strength of evidence
L5 – Prognosis of Disease
Prognostic indicators and their definitions [x2]
(1) 5-year survival rate
Proportion of patients who are alive 5 years after diagnosis
(2) Median survival time
Duration that half of the study population survives
(3) Case fatality rate (CFR)
Proportion of deaths from a certain disease compared to total number of patients diagnosed over a period of time
(4) Response rate
Proportion of patients showing evidence of improvement following an intervention
(5) Remission rate
Proportion of patients entering a phase in which disease is no longer detectable
(6) Recurrence rate
Proportion of patients whose disease have returned after a disease-free interval
Application of prognostic indicators by providing example of conditions/diseases [x4]

(1) 5-year survival rate → 64.9% (colorectal cancer), <1% (diffuse intrinsic pontine glioma), 18.1% (lung cancer)
(2) Median survival time → 10 years (colorectal cancer), 9 months (DIPG), ~6 months (lung cancer)
(3) Case fatality rate (CFR) → 20 died in a group of 400 individuals diagnosed with acute MI | CFR = (20 ÷ 400) × 100%
Rationale of studying prognosis [x6]

✓ Decision on appropriate treatment
✓ Discussion with patients or relatives concerning the management
✓ Dictate the need for rehabilitation or even for a change in the occupation or lifestyle of a patient
✓ Prevent treatment-induced adverse outcomes
Differences and similarities between prognosis and diagnosis [x9]

Diagnosis Prognosis
Differences Differences
Identifies disease via examination Predicts the course of a disease and its treatment
Concerns current condition of patient Concerns future development of patient’s condition
Similarities
Type of outcome is often binary
The same measures are used for assessing model performance
Differences between prognostic factors and risk factors [x1]

No. Prognostic factors Risk factors
1. Definition Definition
Characteristic of a patient that can be used to estimate the Any characteristic or exposure of an individual that
chance of recovery or the chance of the disease recurring increases the chance of developing a disease
2. A person with disease A person without disease
3. Outcomes Outcome
5Ds (disability, death, discomfort, dissatisfaction, disease) Onset of disease
4. More frequent rates Less frequent rates
Definition of prognosis
Possible outcome of a disease and the frequency that they can be expected to occur where it makes prediction of the course of the
disease following its onset
Examples of prognosis tools

a) MELD (Model for End-Stage Liver Disease score) → severity of chronic liver disease
b) CHA2DS2-VASc → risk of stroke in patients with atrial fibrillation
c) CURB-65 → pneumonia mortality
d) Triple-negative breast cancer → checks for oestrogen receptors, progesterone receptors, and excess HER2 protein
L6 – Life Tables
Life table calculation [x1]
Time (t) Alive at Death at the end Probability of Probability of Probability of
beginning of time of time (dt) dying at time surviving at time surviving until
(Lt) (dt/Lt = qt) (1 – qt = pt) time [S(t+)]
1 200 20 20/200 = 0.10 1 – 0.10 = 0.90 0.90 × 1 = 0.90
2 180 30 30/180 = 0.17 1 – 0.17 = 0.83 0.90 × 0.83 = 0.75
3 150 40 40/150 = 0.27 1 – 0.27 = 0.73 0.75 × 0.73 = 0.55
4 110 25 25/110 = 0.23 1 – 0.23 = 0.77 0.55 × 0.77 = 0.42
5 85 15 15/85 = 0.18 1 – 0.18 = 0.82 0.42 × 0.82 = 0.34
Definition of life table [x6]

A table which shows, for a person at each age, what the probability is that they die before their next birthday
Uses of life table [x5]

• Mortality rate
• Probability of dying at each age
• Chance of survivorship
• Life expectancy of population at varying ages
• Average remaining years of life
• Make predictions on demographic or different populations
Inputs and outputs of life table [x6]

Input
• Number of living people at all individual ages in a specific period
• Number of deaths that occurs at these ages in a specific period
Output
• Probability of living at different ages
• Remaining life expectancy at different ages
• Proportion of original birth cohort that is still alive
Definition of survival analysis [x1]

→ A collection of statistical procedures for data analysis for which the outcome variable of interest is time until an event occurs
→ Accommodates data from RCT or cohort study
→ Subjects are followed up for a period of time and data is analysed
→ The duration of study may be days, months, or even years
Types of data obtained from survival analysis [x1]

Probability of surviving, and mortality rate
Definition of censoring [x1]

Censoring is when we do not know the exact survival time
Types of censored data [x1]

1) Left-censored data
- Occurs when we do not know when the patient has the inclusion event
- Example: survival of HIV patient where we do not know for how long the patient has had HIV
2) Right-censored data
- Study ends and no event occurs

- Loss of follow-up procedures
- Withdrawal from study
Objectives of survival analysis

→ Estimate and interpret survivor and/or hazard functions from survival data
→ Compare survivor and/or hazard functions
→ Assess relationship of explanatory variables to survival time
Kaplan-Meier limitations
• Permits comparisons between patient groups or between different therapies
• Cannot be used to measure impact of continuous variable on probability of event
• Cannot quantify risk of event according to value of a variable
Cox proportional hazard model

• Statistical method that determines a cumulative probability of an event and also accounts for impact of other variables upon
that probability
• Independent variables → continuous or discrete
• Merger of logistic regression and life table analysis
L7 – Compliance of Disease
Definition of compliance [x5]
Extent to which a person’s behaviour coincides with medical or health advice
Definition of adherence [x2]

Extent to which a person’s behaviour matches exactly the agreed recommendations from the prescriber
Objective strategies in detecting low compliance [x5]

a) Direct method
✓ Directly observed therapy
✓ Measurement of level of medicine/metabolite in blood
✓ Measurement of biologic markers in blood
b) Indirect method
✓ Patient questionnaires or self-reports
✓ Pill counts
✓ Medication Possession Ratio (MPR)
✓ Assessment of patient’s clinical response
✓ Electronic medication monitors
✓ Patient diaries
Ways of increasing compliance [x5]

• Improve doctor-patient relationship
• Get family members to monitor adherence
• Simplify treatment regime
• Provide continuous health education to the patient/subject
Clinical trials
• Provide detailed and thorough study protocol for compliance in clinical trials
• Offer assistance towards subject’s personal problems
• Discuss with the subject with regards to study period prior to enrolment
Reasons for non-compliance [x2]

No. Reason Examples
1. Socioeconomic factors Low literacy | Low education | Low income | Poor social support | Lack of health insurance
coverage | Family instability | Homelessness
2. Healthcare system Poor quality of doctor-patient relationship | Limited access to healthcare | Difficulty of
scheduling appointments | High drug cost
3. Condition-related Asymptomatic | Chronic diseases | Diseases with long latency of treatment efficacy |
Psychiatric illnesses | Sensitive issues (STDs/HIV)
4. Patient-related Physical impairments | Lack of motivation | Self-efficacy | Denial of disease | Food taboos
and beliefs | Alcohol and substance abuse
Reasons for non-compliance in clinical trials

No. Reason Examples
1. Subject No interest with research findings | No proper explanation from researcher | Intervention
with daily activities/work schedule | Undesirable side effects
2. Researcher Poor communication with subject | Poor implementation of study protocol
3. Study protocol Unclear research protocol | Difficult treatment regime | Lengthy study period
Definition of concordance
Agreement that is reached after a discussion between healthcare provider and patient
Ways of non-compliance
 Patient does not take medicine at all
 Improper dosages are taken
 Not taken in a timely manner
 Medicine is taken along with unprescribed drugs including traditional medicine
 Not following advice on nutrition
L8 – Quality of Life
Definition of QALY and DALY [x6]
QALY (quality-adjusted life year)
Measure of disease burden, including both the quality and the quantity of the life lived. It is used in assessing the value for money
of a medical intervention.
DALY (disability-adjusted life year)
Measure of overall disease burden, expressed as the number of years lost due to ill health, disability, or early death.
What is “Physical Quality of Life Index”? [x6]

• One composite index form numbers of health indicators for QOL
• Consolidates 3 indicators: (1) infant mortality, (2) life expectancy at age 1, and (3) literacy
• These 3 indicators measure the results rather than the inputs and it is calculated by averaging 3 indicators giving equal weight
to each of them
Factors affecting quality of life [x1]

No. Factors Examples
1. Psychological Positive/negative feelings | self-esteem | body image
2. Physical General health | mobility | pain | daily activities
3. Social relationships Personal relationship | sexual activity | social support
4. Environment Physical safety and security | home environment
5. Spirituality Faiths and beliefs | religions
6. Independence Financial resources | work satisfaction | freedom
Importance of HRQOL measures

• Provide valuable insights into relationships between HRQOL and risk factors
• Determine burden of preventable diseases
• Understanding patients’ POV about disease and treatment methods applied
• Provide important considerations when comparing different treatment methods and evaluating interventions
• Monitor progress in achieving nation’s health objectives
L9 – Good Clinical Practice

Definition of good clinical practice [x8]
International ethical and scientific quality standard for the designing, conducting, recording, and reporting of clinical trials that
involve the participation of human subjects
Components of good clinical practice [x2]

✓ Rights, safety, integrity, confidentiality, and well-being of trial subjects are protected consistent the principles that have their
origin in Declaration of Helsinki
✓ Data and reported results are credible and accurate
Responsibilities of Institutional Review Board (IRB) [x7]

1. Safeguard the rights, safety, and well-being of all trial subjects
2. Review documents:
- Trial protocol
- Written informed consent forms
- Written information to be provided to the subjects
- Investigator brochure
- Available safety information
- Information about payment and compensation available to subjects
- Investigators’ CV
3. Review a proposed clinical trial within a reasonable period of time and documents its views in writing
4. Consider qualifications of the investigators
5. Conduct continuing review of each ongoing trial at intervals appropriate to the risk of to human subjects (at least once a year)
6. Request more information
7. Non-therapeutic trial protocol review
8. Review situations where consent is not possible to ensure that ethical concerns are addressed
9. Review amount and method of payment to subjects to ensure absence of coercion or undue influence on trial subjects
Why is informed consent reviewed by IRB? [x1]

To ensure the absence of coercion or undue influence on trial subjects during the process of giving consent to the trial
Steps in collecting consent in research [x4]

1. Provide informed consent form.
2. Make sure there is no coercion or undue influence by study investigators.
3. Fully inform participant of all aspects of the trial.
4. Ensure the consent has been signed and dated by the subject.
5. All subjects must receive a signed copy of the consent.
Principles of ICH GCP [HIGHLIGHTED]

1. Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki.
2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against anticipated benefit for individual
trial subject and society.
3. The rights, safety, and well-being of trial subjects are the most important consideration.
4. The available non-clinical and clinical information on investigational product should be adequate to support the proposed
clinical trial.
5. Clinical trials should be scientifically sound and described in a clear, detailed protocol.
6. Trial should be conducted in compliance with the protocol.
7. Medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified
physician or dentist.
8. Each individual involved in conducting a trial should be qualified by education, training, and experience.
9. Freely given informed consent should be obtained from subjects prior to clinical trial participation.
10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation
and verification.
11. The confidentiality of records that could identify subjects should be protected.
12. Investigational products should be manufactured, handle, and stored in accordance with applicable good manufacturing
practice (GMP) with approved protocol.
13. Systems with procedures that assure the quality of every aspect of the trial should be implemented.
Definition of clinical research

Branch of medical science that determines safety and effectiveness of medications, devices, diagnostic products, and treatment
regimens intended for human use
Declaration of Helsinki
➢ Outlines basic principles for medical research
➢ Duty of physician to patient’s health
➢ Basis for good clinical practice
➢ Derived from Nuremberg code
Benefits of treatment guidelines

✓ Disease-specific standards
✓ Improve healthcare provider decision-making
✓ Ensure consistency in medical practice and conform with evidence-based medicine
✓ Ensure quality of care
✓ Control healthcare costs
L10 – Efficacy of Treatment

Definition of efficacy and effectiveness of treatment [x1]
Efficacy: Investigate benefits and harms of an intervention under highly controlled conditions
Effectiveness: Examine interventions under circumstances that more closely approach real-world practice
Differences between efficacy and effectiveness [x2]

No. Efficacy Effectiveness (pragmatic)
1. Investigate benefits and harms of an intervention under Examine interventions under circumstances that more
highly controlled conditions closely approach real-world practice
2. ‘Ideal’ setting Real-world everyday clinical setting
3. Highly selected, homogenous population Heterogenous population
4. Highly experienced and trained providers Representative usual providers
5. Strictly enforced intervention Interventions are applied with flexibility
Definition of therapeutic index [x1]

The range of dose of the drug which shows the highest efficacy and lowest toxicity
Two types of biases that can occur in clinical trials

• Selection bias
• Performance bias
Solutions to ensure biases listed above do not occur

Selection bias Performance bias
• Do randomisation which is the process of assigning • Do masking in order to reduce bias related to prior
participants to groups so that each participant has an knowledge or beliefs about treatment effects on the
equal chance of being assigned to a given group performance of the trial and on the reporting outcomes
• Types of randomisations: • Promotes objectivity in: data reporting, data collection
1. Simple randomisation and follow-up, outcome assessment, and data
2. Restricted randomisation interpretation
3. Adaptive randomisation • Types: single, double, triple
Definition of clinical trial

A set of procedures in medical research conducted to allow safety and efficacy data to be collected for health interventions
Types of clinical trials

a) Treatment trials
Tests new treatment/combination of drugs/approaches to surgery/radiation therapy
b) Prevention trials
- Looks for better ways to prevent diseases in people who have never had the disease
- Finds ways to prevent a disease from returning
- Approaches include: medicines/vitamins/vaccines/minerals/lifestyle changes
c) Screening trials
Tests the best way to detect certain diseases or health conditions
d) Quality of life trials
Explore ways to improve comfort and quality of life for individuals with chronic illnesses
Trial design types

Parallel, crossover, cluster randomisation, factorial, adaptive
Parallel trial design

→ Simultaneous treatment and control group
→ People are randomly assigned to one treatment group
→ Randomisation removes treatment selection bias and promotes comparability of treatment groups
→ Statistical comparisons are made between treatment groups
Definition of randomisation and masking

Randomisation: Process of assigning participants to groups so that each participant has an equal chance of being assigned to group
Masking: Also known as blinding, it is a process where treatment assignment is not known after randomisation
Rationale of randomisation
- Avoids selection bias
- Tends to produce comparable treatment groups
- Has a defined time point for trial entry
Rationale of masking
• To reduce bias related to prior knowledge
• Prevent performance bias and detection bias
• Promotes objectivity in: data reporting, data collection, outcome assessment, data interpretation
L11 – Quality Assurance in Hospital Practice

Quality improvement activities [HIGHLIGHTED]
• Maternal Mortality Review/Perinatal Mortality Review
• Clinical Practice Guidelines (CPG)
• National Indicator Approach (NIA)
• Health Technology Assessment (HTA)
• Hospital Accreditation
• STAR Rating
• Key Performance Indicators (KPI)
• International Organisation for Standardisation (ISO)
Process in Quality Assurance Cycle [x1]

Problem
identificat
ion
Re-evaluation of Problem
the problem prioritisation
Implementation
Problem
of remedial
analysis
actions
Quality
Identification of
assurance
remedial actions
study
Definition of quality assurance [x2]

A system of activities for ensuring production of defined service to agreed standards within given resources
Definition of quality in patient care [x2]
Securing optimum achievable result for each patient, avoidance of iatrogenic complications and giving attention to the patient and
family needs in a manner that is cost effective and reasonably documented
Quality approaches for patient care services by MOH [x1]

• National indicator approach (NIA)
• District specific approach (DSA)
• Hospital specific approach (HSA)
Objectives of QA [x3]
• Monitoring quality of various services
• Detect shortfalls
• Investigate the cause
• Institute appropriate corrective measures
Definition of Shortfall in Quality (SIQ) [x1]

Performance below expected standard
Steps in management of SIQ [x2]

1) Entry point → Case review at sentinel event or rate-based during clinical audit
2) Data verification
3) Do root cause analysis (RCA)
4) Compare with model of good care (MOGC)
5) Remedial action
6) Evaluate effectiveness
Factors of SIQ [x1]

• Patient factor – presence of comorbidities
• Work and environment care – equipment malfunction
• Staff factor – low competency
• Team – verbal and non-verbal communication
Importance of QA in hospital practices [x1]

• To provide the best care

• Technology demands for accountability
• Increase awareness of medico-legal implications
• Need for continuous quality improvement
Quality assurance practices (QAP) indicators

(a) Broad generic indicators
- Hospital mortality
- Surgical site infections
- Unplanned admissions
(b) Specialty-specific audits
- ICU audit
- Nosocomial infection survey
(c) Professional QA
- Complaints
- Incident reporting
- Adverse outcomes
L12 – Meta-analysis
Definition of systematic review [x1]
Attempt to collate all empirical evidence that fits pre-specified eligibility criteria in order to answer a specific research question
Phases of meta-analysis [x1]

1. Identify relevant research → PubMed, EMBASE, CENTRAL
2. Check between study heterogeneity → Cochran Q test, I2
3. Meta-analysis → fixed/random effect model, Forrest plot
4. Evaluate sources of heterogeneity → subgroup analysis, sensitivity test, meta-regression
5. Check publication bias → funnel plot, Egger’s regression test, trim and fill method
6. Present meta-analysis result based on PRISMA
Hierarchy of evidence in meta-analysis [x2]

From lowest to highest quality:
Benefits of meta-analysis [x4]

1. Increase power and precision – detect effect as statistically significant and narrower CIs
2. Quantify effect sizes and their uncertainty – reduce problems of interpretation due to sampling variation
3. Assess homogeneity/heterogeneity of results – quantify among study variation

4. Settle controversies arising from conflicting studies – generate new hypotheses
Definition of meta-analysis [x2]

An optional component of systematic review which is a statistical analysis of a large collection of analysis results from individual
studies for the purpose of integrating the findings (Glass, 1976)
Reasons for performing test of heterogeneity [x1]

To check for differences in the findings of primary studies using Cochran’s Q test and I 2 value
Interpretation and conclusion of meta-analysis findings [x1]

1. Cochran’s Q test → determine presence of differences between studies
→ Any variation seen is due to chance
→ P < 0.10 = heterogeneity is present
→ P > 0.10 = heterogeneity is absent
2. I2 value → represents the proportion of between studies variability that ranges from 0-100%
→ ≥ 50% = moderate heterogeneity
→ ≥ 75% = high heterogeneity
3. Risk ratio/relative risk
→ RR = 1 → no difference or little difference in risk
→ RR > 1 → increased risk of that outcome in the exposed group
→ Example: RR = 3.2 → those who had incidental appendectomy had 3.2 times the risk of getting a post-operative
wound infection
→ RR < 1 → decreased risk of that outcome in the exposed group
→ Example: RR = 0.58 → those who took low-dose aspirin had 0.58 times the risk of MI compared to those who did
not take aspirin
What are fixed and random effect model?

(1) Fixed effect model
- Assumes studies are identical
- Assumes true effect is the same in all studies
- Used when studies are homogenous only
(2) Random effect model
- Assumes there is a distribution of true effects
- Can be used when studies are homogenous or heterogenous
(3) Bayesian meta-analysis
Alternative to both fixed and random effect model
Key characteristics of a systematic review

• Clearly stated set of objectives with pre-defined eligibility criteria for studies
• Explicit and reproducible methodology
• Systematic search that attempts to identify studies that would meet eligibility criteria
• Assessment of validity of the findings of included studies (e.g., assessment of risk of bias)
• Systematic presentation and synthesis of characteristics and findings of included studies
Types of meta-analysis
a) Standard pair-wise meta-analysis
- Obtain size of effect from similar studies estimating the same effect
- Example: mechanical vs. manual chest compressions for cardiac arrest
b) Network meta-analysis
- Compare multiple interventions for the same condition
- Example: medical intervention for primary open angle glaucoma
c) Meta-regression
- Investigate relationship between size of an effect and some characteristics of the studies
- Example: Association of efficacy of BCG vaccine with latitude
Funnel plot
• Plots effect size against sample size of the study
• Symmetry → no publication bias
• Asymmetry → possible publication bias
SLP6 – Ethics in Clinical Research

Ethical principles for clinical research [x1]
The Belmont Report 1979 introduced 3 ethical principles:
1. Respect for person
- Individuals must be treated as autonomous agents
- People with diminished autonomy must be protected
2. Beneficence and non-malfeasance
- Do not harm
- Maximise possible benefits and minimise possible harms
3. Justice
All individuals must be treated fairly
Seven requirements for ethical research

1) Societal/scientific value
Treatment or hypotheses being tested should improve health or increase knowledge about research area
2) Scientific validity
Avoid exploitation and ensure accuracy of outcomes
3) Fair subject selection
Entails decisions about who will be included and developing strategy for recruiting subjects
4) Favourable risk-benefit ratio
→ Most important responsibility of an IRB/IEC
→ To ensure risks to individuals are minimised
→ Benefits are enhanced
→ Benefits are proportionate or outweigh the risks
5) Respect for subjects
Protect subject’s confidentiality and privacy, provide opportunities to withdraw, and monitor subject’s well-being
6) Informed consent
→ Text should not coerce or induce participation
→ Language should be understandable to subjects
→ Ample time should be provided to subjects in order to make decisions
→ Informed consent form must be signed and dated by subject before participation
7) Independent review
- Minimise impact of conflicts of interests
- Important for social accountability
Important vulnerable and underrepresented groups

Children, women, emergency patients, population of developing countries, minorities, fetus and embryo (vulnerable only), etc.

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MM20802: Epidemiology in Clinical Practice Notes 21/22

L1 – Use of Epidemiology in Clinical Practice

Clinical issues in practice of medicine [x2]

Preventive measures with the use of epidemiology [x1]

Types of normal and examples [x2]

Differences between epidemiology and medicine

Basic properties of the normal distribution curve

Normal in the context of medicine

Ways to distinguish normal from abnormal

Predictive value of a test

Would you recommend [insert test] as a screening/diagnostic tool? Explain. [x10]

Conclusion written based on calculation [x2]

Criteria for starting screening programmes

Criteria for suitable screening test

Differences between mass screening and diagnostic examinations

L4 – Diagnostic Strategy and Clinical Disagreement

Definition of clinical diagnosis [x1]

Definition of clinical disagreement [x1]

Reasons for clinical disagreement

Use of clinical epidemiology to improve diagnostic accuracy

Application of prognostic indicators by providing example of conditions/diseases [x4]

Rationale of studying prognosis [x6]

Differences and similarities between prognosis and diagnosis [x9]

Differences between prognostic factors and risk factors [x1]

Examples of prognosis tools

Definition of life table [x6]

Uses of life table [x5]

Inputs and outputs of life table [x6]

Definition of survival analysis [x1]

Types of data obtained from survival analysis [x1]

Definition of censoring [x1]

Types of censored data [x1]

- Study ends and no event occurs

Objectives of survival analysis

Cox proportional hazard model

Definition of adherence [x2]

Objective strategies in detecting low compliance [x5]

Ways of increasing compliance [x5]

Reasons for non-compliance [x2]

Reasons for non-compliance in clinical trials

What is “Physical Quality of Life Index”? [x6]

Factors affecting quality of life [x1]

Importance of HRQOL measures

L9 – Good Clinical Practice

Components of good clinical practice [x2]

Responsibilities of Institutional Review Board (IRB) [x7]

Why is informed consent reviewed by IRB? [x1]

Steps in collecting consent in research [x4]

Principles of ICH GCP [HIGHLIGHTED]

Definition of clinical research

Benefits of treatment guidelines

L10 – Efficacy of Treatment

Differences between efficacy and effectiveness [x2]

Definition of therapeutic index [x1]

Two types of biases that can occur in clinical trials

Solutions to ensure biases listed above do not occur

Definition of clinical trial