SELECTION BIAS : One of the key purposes of randomization is to avoid selection bias, and intention-to-treat (ITT)

analysis preserves the balance of similar characteristics between the treatment and placebo group that was created
by randomization. Even though patients may agree to be in the groups to which they are randomly assigned, it is quite
possible that they will not adhere to their assigned treatment or drop out, which could ultimately result in crossover
patients to the control group. ITT analyzes data based on initial study assignment, not on whether participants
remained fully committed to their assigned group.

INTERNAL VALIDITY: Internal validity reflects whether a study has actually measured what it sought to measure. This
study aims to assess the treatment efficacy of pulmharkimab versus a placebo. Because an intention-to-treat (ITT)
analysis combines treatment-adherent and treatment-nonadherent groups (in a single treatment group), it is likely
that ITT analysis results in a lower estimate of drug efficiency than is actually the case, and thus results in
decreased internal validity

Bias

 Definition: an error in the study design or way in which it is conducted that causes systematic deviation of
findings from the truth

Types of bias

Bias Problem Example Solution

Selection
 The individuals in a sample  Healthy worker effect: The working  Randomization
bias group are not representative population is healthier on average than
 Subjects are randomly assigned
of the population from which the general population → Any sample to the intervention and control
the sample is drawn. consisting of only working individuals groups to ensure that both
does not represent the general groups are roughly equal in
population. baseline characteristics(often
 Berkson bias: Sample groups drawn displayed in a table, e.g.,
from a hospital population are more in randomized controlled
likely to be ill than the general trials).
population.  Controls for both known and
 Non-response bias: Responder unknown confounders
characteristics differ significantly from Successful if
nonresponder characteristics because possible confounding
nonresponders do not return characteristics (e.g.,
information during a study (e.g., socioeconomic demographics,
patients do not return a call or do not family history) are
respond to a written survey response). approximately equally
 Volunteer bias: Individuals who distributed between the groups
volunteer to participate in a study have
 Ensure the sample group is
different characteristics than the representative of the
general population. population of
 Attrition bias interest (e.g., in case-control
 Selective loss to follow up of studies).
participants; especially in prospective  Collect as much data on
studies characteristics of the
 Risk of over- or underestimating the participants as possible.
 Types of bias

Bias Problem Example Solution

association between exposure and  Nonresponder characteristics

outcome because the remaining
participants differ significantly from
those lost to follow-up.
 Survival bias
 Also known as prevalence-incidence
bias or Neyman bias
 A type of selection bias in which those
observed as having a disease have
either more severe or less severe
disease than is true for all those who
truly have the disease. In comparison to
the true population with disease:
 If those with severe disease die before
the moment of observation, those with
less severe disease are observed
 If those with less severe disease have a
resolution of their disease before the
moment of observation, those with
more severe disease will be observed.
 Typically occurs in case-
control and cross-sectional studies.
should not be assumed and
incorrectly included in data
analysis; instead, undisclosed
characteristics of
nonresponders should be
recorded as unknown.
Intention-to-treat analysis: All
patients who initially enrolled
in the study (including drop-
outs) are included in the
analysis of study data; helps to
reduce selection
bias; preserves randomization

Allocation
 
A systematic difference in the Assigning all female patients to one  Randomization
bias way that participants are group and all male patients to another
assigned to treatment or group
intervention groups

Recall bias
 Awareness of condition by  
Subjects recall a certain exposure after ↓ Time to follow-up in
subjects changes their recall finding out about others with the same retrospective studies
of related risk condition (e.g., retrospective cohort
factors; common in studiesor case-controlstudies)
retrospective studies

Information
 Incorrectly collected data  
Insufficient information about exposure Standardize data collection
bias and disease frequency among subjects
 Information is gathered differently
between the treatment and control
group
 Reporting bias: selective disclosure or
suppression of information or study
results, resulting in underreporting or
over reporting of exposure or outcome
 Types of bias

Bias Problem Example Solution

 Interviewer bias: different interviewing

approaches towards exposed and
unexposed groups, or cases and
controls, prompt different responses
between groups and the conclusion of
systematic differences between groups
when there are none.

Cognitive
 
Tendency to favor something Response bias: study participants do  Use of placebo
bias because of personal beliefs or not respond truthfully or accurately  Researchers are discrete about
ideas because of the manner in which their observations
questions are phrased (e.g., leading  Prolong the time of observation
questions) and/or the possibility of to monitor long-term effects
more socially acceptable answer  Blinding
options; especially common in surveys
 Observer bias (Experimenter-
expectancy effect or Pygmalion
effect): measurement of a variable or
classification of subjects is influenced
by the experimenter's knowledge or
expectations
 Confirmation bias: the tendency of the
investigator to include only those
results which support his/her
hypothesis and ignore the rest
 Hawthorne effect: subject's change their
behavior once they are aware that they
are being observed; especially relevant
for psychiatric research; difficult bias to
eliminate
 Placebo and nocebo effects: effect of
the subject's preconceptions/beliefs on
the outcome

Lead-time
 
Lead time: the average length Often discussed in the context of  Measure the back-end survival
bias of time between detection of a cancer screening  Gold standard of
disease and the  Lead-time bias occurs when survival measuring screening test
predetermined outcome times are chosen as an endpoint effectiveness is to use mortality
 Early detection of disease is of screening tests rates instead of survival times
misinterpreted as increased
survival

Length- An apparent improvement in Often discussed in the context of  Arrange patients according to
 Types of bias

Bias Problem Example Solution

time bias the duration of survival when cancer screening severity of disease
a terminal disease with a long
clinical course (e.g., slow-
growing tumor) is screened.

Surveillance
 An outcome (e.g., disease) is
bias diagnosed more frequently in
a sample group than in the
general population because of
increased testing and
monitoring.
 Leads to falsely
high incidence and prevalence
rates

Subjects who receive the trial treatment Comparing to an
are monitored more frequently unexposed control groupwith a
similar likelihood of screening
 Selecting an outcome that is
possible in both the exposed
and unexposed group

LATENCY- can be short for infectious disease or long for diseases like cancer, heart disease.

-concept can be extended to risk factors and risk reducers.

-sometimes significant amount of time must pass before exposure to a risk modifier has a clinically evident effect on
the disease process.

-also exposure to a risk modifier may need to occur continuously over a certain period before the disease outcome is
affected.

Confounding

 Definition: any third variable that has not been considered in the study but that correlates with the exposure
and the outcome
 Example: A confounder can be responsible for the observed relationship between the dependent
and independent variables. For instance, while exposure to coal can result in lung cancer in individuals at a
mining company, many miners smoke cigarettes, which acts as a third variable that can lead to lung cancer.
 Solution
 Perform multiple studies with different populations.
 Randomization
 Crossover study
 Restriction (epidemiology)
 The researcher only studies a part of the population that meet certain criteria (e.g., only males with a
particular disease are included in a study to avoid the influence of gender on exposure and outcome)
  Problems
 Limits generalizability
 Makes obtaining a large sample group difficult
 Matching (epidemiology)
 Commonly used in case-control studies
 Cases and controls are grouped into pairs with similar attributes to avoid confounding
 Problems
 Matching does not completely eliminate confounding
 Can introduce confounding if the investigators match by factors that are not matched in the source population
 Can introduce bias
 Standardization of data (see Z-score)
 Stratified analysis
 Study groups are divided into subgroups according to the third variable.
 Measures of association (e.g., the odds ratio) can be calculated for each subgroup (e.g., stratum-specific odds
ratios)
 In confounding:
 Stratifying participants into subgroups according to the third variable will eliminate the confounder
 The measures of association between subgroups will be similar, but the stratified measure of association is
different from the whole population measure of association (e.g., crude odds ratio)
 In effect modification:
 Stratifying participants into subgroups according to the third variable will result in a stronger relationship in
one subgroup
 The measures of association will differ between subgroups (i.e., there is a strong association in the subgroup
in which the effect modifier is present, while there is no association in the subgroup in which the effect
modifier is absent)

Effect modification

 Definition: a third variable that positively or negatively influences a study outcome; occurs when the exposure
has a different effect between groups; not considered a type of bias in itself
 Example: a certain drug works in children, but does not have any effect on adults
 Solution: stratified analysis
 Effect modification can be differentiated from confounding by performing a stratified analysis: When the
population is stratified according to a factor, different results will be seen if it is a confounderor if it is
an effect modifier.

Latency period

 Definition: A seemingly inactive period between the exposure to a risk modifier to the time its effect becoming
clinically apparent
 Example: The incubation period for infectious diseases is often very short, while there may be a very
long latency period between pathogenesis of a malignancy and clinical manifestation.
Experimental studies

Randomized controlled trials (RCT; interventional studies)

 Aim: determines the possible effect of a specific intervention on a population of interest

 Study method: patients are randomly allocated as either treatment or control subjects , after which they are
monitored and evaluated for the outcome of interest
 Special variants
 Blinding: the practice of not informing an individual or group about which individuals are a control or
treatment candidate; used to minimize bias
 Single-blind study: Only researchers know who is a control or treatment candidate.
 Double-blind study: Neither the researcher nor the study participants know who is a control or treatment
candidate.
 Triple-blind study: The researcher, the study participants, and the person who analyzes the data do not know
who is a control or treatment candidate.
 Cluster randomized controlled trials
 Different participants are grouped together into clusters and then randomly assigned to the control or
intervention groups.
 A cluster RCT is easier to perform than a classical RCT, but may have less validity than a classical RCT.

Clinical drug trials

 Definition: studies involving human subjects to assess new health interventions to provide safe and effective
medical care
 Compares the benefits of a single treatment vs. a placebo or between 2 or more drugs

Clinical Study population Research aim

drug trials

Preclinical Animals Determine the effect, dose, and side effects (teratogenic/carcinogenic potential)
studies of the drug

Phase 0 Small number of Test subtherapeutic doses of a new drug to determine

healthy individuals preliminary pharmacokinetic and/or pharmacodynamic properties of the drug

Phase I Small number of Determine the side effects, toxicity, pharmacokinetics, and pharmacodynamics of
healthy individuals the drug

Phase II Small number of Determine the efficacy, effective dosing, and side effects of the drug
patients with a specific
disease

Phase III Randomized control Compare the new drug with current treatment options or placebo
trial with a large
number of patients
with a specific disease
 Clinical Study population Research aim
drug trials

Phase IV Large number of Ascertain the effects of long-term therapy and effects on special patient groups
patients with a specific (e.g., patients with chronic renal failure); can lead to withdrawal of a drug from
disease after drug the market
approval

Clinical drug trials assess adverse event rates and drug interactions. They can be used to develop warnings and
precautions as well as contraindications for the use of a drug. For example, if the rate of hyperglycemia is significantly
higher in the treatment group compared to the control group, it may not be appropriate for use in patients with
diabetes mellitus.

Factorial study

 Aim: to test the effect and interactions of two or more factors (e.g., treatments)
 Study method: Individuals are randomly assigned to groups receiving different doses and combinations of
drugs.
 Example: In order to study 5 dose levels of a drug X and 2 dose levels of drug Y, 10 different intervention
combinations should be examined.

Crossover study

 Aim: to obtain a more efficient comparison of treatments with fewer patients

 Study method: each patient switches from one treatment to another during the trial period and serves as their
own control
 Example: each patient receives both drug X and drug Y, but at different time periods during the study

Observational studies

Cross-sectional study (prevalence study)

 Aim: to determine the prevalence of exposure and disease

 Study method: the prevalence of disease and other variables (e.g., risk factors ) are measured simultaneously
at a particular point in time(i.e., a snapshot of the population)
 Example: investigating the number of patients with both coronary heart disease as well as hypertension in the
year 1998

Case-control study

 Aim: to study if an exposure is associated with an outcome (e.g., disease)

 Study method

1. Researchers begin by selecting patients with the disease (cases) and without the disease (controls) with
matching baseline characteristics from the same source population.

2. The observer compares the presence of risk factors between these two groups.
 3. The odds ratio is then determined between these groups.
 Example: determining the link between cervical cancer and human papillomavirus (HPV) exposure by
comparing otherwise similar (e.g., same age) patients with and without histologically confirmed cervical
cancer
 Example :Case-control studies are ideal to study conditions like uncommon subtypes of anti-NMDA
encephalitis because they are the most economical way to study a rare disease and its associated risk factors.
The comparison to a control group without anti-NMDA encephalitis helps determine the presence of risk
factors that might be associated with the disease. To assess the strength of association between a risk factor
and disease, the odds ratio is reported. Unlike in cohort studies, in case-control studies the outcome is
determined first (here: anti-NMDA encephalitis), and then the presence of an association with a risk factor
(here: ovarian teratomas) is assessed, retrospectively.

Cohort study

 Aim: to study the incidence rate and whether the exposure is associated with the outcome of interest (e.g., a
disease)
 Study method and examples

Retrospective cohort study

 Starts with individuals who are either exposed or not exposed to a particular risk
factor (e.g., smoking)
 A review of medical records of patients in both groups is then conducted to determine if the
disease of interest (e.g., lung cancer) has developed.
 Retrospective cohort studies can be used to study rare diseases, and they are relatively
inexpensive, as they mainly collect and analyze data from the past. However,
retrospective cohort studies determine the risk factor first (in this case, ovarian teratoma),
and then evaluate the outcome (in this case, new cases of anti-NMDA encephalitis). This
researcher has already determined the outcome (i.e., anti-NMDA encephalitis) and now
wants to see what risk factors are associated with it. Furthermore, while a rare disease as
this subtype of anti-NMDA encephalitis could theoretically be studied in a retrospective
cohort study, its low incidence would make it time-consuming and impractical to find a
group of patients with ovarian teratomas and determine via chart review how many of these
eventually developed anti-NMDA encephalitis.

Prospective cohort study

 Starts with individuals who are either exposed or not exposed to a particular risk
factor (e.g., smoking)
 These two groups are then followed for a period of time to see if the disease of interest
(e.g, lung cancer) develops.

Twin concordance study

 Aim: determines the inheritability of disease vs. environmental risk factors

 Study method: comparing the frequency of disease in twins (monozygotic or dizygotic)
 Example: twins are followed over a 30-year period, following the diagnosis of Hodgkin disease in the first
twin, to see if the frequency of cancer differed between monozygotic and dizygotic twins
Adoption study

 Aim: determines the inheritability of disease vs. environmental risk factors

 Study method: comparing the frequency of disease in adopted children vs. children who live with their
biological parents
 Example: the prevalence of schizophrenia in adopted children and the prevalence of schizophrenia in children
who live with their biological parents is compared to determine the influence of genetic and environmental
factors on schizophrenia

Randomized controlled trials are considered the gold standard for clinical trials!

A case-control study compares a small population group over a short period of time (less cost-intensive) and
determines how multiple exposures lead to one outcome; a cohort study compares a large population over a long
period of time (more cost-intensive) and determines how one exposure leads to multiple outcomes!

In cohort studies, researchers select individuals based on exposure first and then determine if these individuals develop
a disease. This is in contrast to case-control studies, in which patients with disease (cases) and those without disease
(controls) are selected first to determine if they were exposed or not!

Principles of study design

 Study designs should be tailored to the question that needs to be answered.

 A good study design with high levels of evidence increases the strength of conclusions drawn from the
results.

Types of epidemiological studies

Description Example

Descriptive  Studies that try to identify individual  Case report

studies characteristics (age, sex,
occupation), place (e.g., residence,  Case series
hospital), or time of events (e.g.,
during diagnosis, reporting) in  Ecological study
relation to an outcome (e.g.,
disease).  Cross-sectional study

Analytical  Studies that determine the  Experimental studies

studies relationship between an exposure
and outcome  Studies that include an intervention

 Always involve a comparison group  The independent variable is

manipulated to determine the effect on
the dependent variable.

 Randomized control trial

 Description Example

 Observational studies

 Studies without an intervention

 The independent variable is not

manipulated.

 Cohort study; Case-control

study, Cross-sectional study

Interpretation

 Epidemiological studies suggest relationships between two events (e.g., exposure and disease).

 This comparison can be measured using rates, proportions, and/or ratios.

 Ratios: comparison of two related or unrelated values

 Proportion: comparison of one part of the population to the whole

 Rates: measure of the frequency of an event in a population over a specific period of time

 These measures determine the strength of association between two events and allow us to describe population
characteristics (e.g., detect populations at risk) and quantify morbidity/mortality.

 Furthermore, researchers can eventually develop hypotheses about why these groups are at risk.

Case report

 Description: a report of a disease presentation, treatment, and outcome in a single subject or event

 Example: report of a single case of cervical cancer in a 25-year-oldfemale subject

Case series report

 Description: a report of a disease course/response to treatment compiled by aggregating several

similar patient cases

 Example: collecting and reporting several cases of pericarditis at a local hospital

Ecological study

 Aim: to identify an exposure associated with an outcome (e.g., disease), especially if the outcome is
rare

 Study method: assesses aggregated data where at least one variable (e.g., an outcome) is at a
population level and not an individual level

 Example: determining the incidence of cholera deaths based on specific locations (e.g., different
parts of a city) to identify the exposure (e.g., water from a single contaminated pump)
MEASURES OF RISK

 Risk factors: variables or attributes that increase the probability of developing disease or injury

 The variables in the formula below stand for the following:

With disease Without disease

Exposed a b

Not exposed c d

Absolute risk

 ∼ Incidence rate

 Measures the probability of acquiring disease/injury in a given study population

 Used in cohort studies

 Formula: (number of new cases) / (total individuals at risk of developing disease) = (a + c)/(a + b + c + d)

Relative risk (RR; risk ratio)

 The risk of an outcome (e.g., disease) among one group compared to the risk among another group

 Measures how strongly a risk factor (e.g., death/injury/disease) in exposed individuals is associated with an
outcome

 Used in cohort studies

 Considered statistically significant if the corresponding p-value is < 0.05

 Formula: (incidence of disease in exposed group) / (incidence of disease in unexposed group) = (a/(a +
b))/(c/(c + d))

Attributable risk (AR)

 The proportion of cases in exposed individuals that can be attributed to the exposure

 Used in cohort studies

 Formula

 Population AR: (incidence rate entire study population) - (incidence rate in unexposed group) = ((a +
c)/(a + b + c + d)) - (c/(c + d))

 Exposure AR: (incidence rate in exposed group) - (incidence rate in unexposed group) = a/(a + b) -
c/(c + d)
Attributable risk percent (ARP)

 The percentage of incidence of disease among exposed individuals that can be attributed to the exposure

 Formula

 ARP = (RR - 1)/RR i.e. (Risk in exposed- risk in unexposed/risk in exposed)

 Alternatively, ARP = AR/(incidence of disease in exposed group) * 100

Odds ratio (OR)

 Compares the odds of exposure in individuals with disease/injury to those without disease/injury

 Used in case-control studies

 Rare disease assumption

 Since case control studies do not track patients over time, relative risk cannot be calculated.

 However, the assumption can be made that if an outcome is rare (e.g., the prevalence of a disease),
the incidence of that outcome is low, and the odds ratio (OR) approximates the relative risk (RR)

 Example: surgical hypertension in MEN 2 Q: It assumes that if the incidence of a study's outcome
(surgical hypertension during pheochromocytoma resection) is low (i.e., the disease is rare), the odds
ratio approximates the relative risk. Usually the relative risk cannot be established in case-control
studies, as subjects are not tracked over time. Instead, the odds ratio is calculated to determine
whether there is an association between an exposure (MEN2 syndrome) and outcome
(surgical hypertension), although the odds ratio does not provide a quantitative estimate of the risk.
Because surgical hypertension during pheochromocytoma resection is rare, the rare disease
assumption holds that OR is approximately equal to RR. It can thus be assumed that the risk of
surgical hypertension during pheochromocytoma removal is 3.4 times greater in patients with MEN
type 2 syndromes than in patients without MEN2 syndromes.

 Formula

 Odds

 The probability of an event occurring divided by the probability of this event not occurring

 Odds of disease in exposed group = cases exposed/cases not exposed

 Odds of disease in unexposed group = controls exposed/controls not exposed

 OR = (odds of disease in exposed group)/(odds of disease in unexposed group) = (a/c) / (b/d)

 OR = 1 means the event is equally likely in both groups.

 OR > 1 means the event is more likely to occur in the group exposed to the risk factor.

 OR < 1 means the event is less likely to occur in the group exposed to the risk factor.

Relative risk reduction (RRR)

  The proportion of decreased risk due to an intervention compared to the control group

 Formula: 1 – RR

 When given as a table, eg intervention group had 10% and control group had 17%, RRR is calculated using
control-intervention/control (17-10/17=0.41=41%)

Absolute risk reduction (ARR)

 The difference in risk as a result of an intervention compared to the control group (e.g., risk of death)

 Formula: risk in intervention group – risk in control group= (c/(c + d)) – (a/(a + b))

 When given as a table, eg intervention group had 10% and control group had 17%, ARR is calculated using
control – intervention (17-10=7)

 EG- After 2 years, 50 out of 500 patients were still alive in the control group compared to 100 out of 500
patients in the treatment group. The risk of death for the control group was 450/500 = 0.90. The risk of
death for the treatment group was 400/500 = 0.80. The absolute risk reduction (ARR) is the difference in
death rates (0.9 - 0.8 = 0.1). The numbers needed to treat (NNT) is the inverse of the ARR (1/0.1 = 10). In
other words, on average, ten patients must be treated with Noxbinle 100 mg instead of Metalimus 100 mg to
prevent one additional death from hepatocellular carcinoma.

Number needed to treat (NNT)

 The number of individuals that must be treated, in a particular time period, for one person to benefit from
treatment (i.e., not develop disease/injury)

 Formula: 1/absolute risk reduction (ARR)

 The ideal value for NNT =1. This means that for every patient who receives a treatment or intervention, one
patient benefits.

 NNT is more practical at estimating an interventions benefit than the ARR or other measures (eg, relative risk
ratio).

Number needed to harm (NNH)

 The number of individuals who need to be exposed to a certain risk factor before one person develops
disease/injury

 Formula: 1/attributable risk (AR)

Hazard ratio

 The measure of an effect of an intervention on an outcome (death/cure) over a period of time

 Used in survival analysis

 Formula
  (incidence of disease in exposed group)/ (incidence of disease in unexposed group) = (a/(a +
b))/(c/(c + d))

 HR = 1 : no relationship

 HR > 1 : the event (the outcome of interest e.g., death, cure) is more likely to occur in the
exposed group

 HR < 1: the event is less likely to occur in the exposed group

 Confidence interval containing null value of 1 also indicates no significant difference

between both groups.

Dose-response relationship (epidemiology)

 One of the criteria required to establish causality in epidemiological studies

 Refers to the presence of a dose-response curve (e.g., the presence of disease increases/decreases in direct
proportion with the level of exposure)

 A causal dose-response relationship assumes that the greater the exposure, the greater the risk of disease

 Can be influenced by confounding

The relative risk, odds ratio, and hazard ratio are usually displayed with a corresponding p-value. Per convention, they
are consideredstatistically significant, if the related p-value is < 0.05!

Some of the key criteria for causality include:

(a) exposure preceding the outcome,

(b) strength of association,

(c) increased amounts of exposure leading to increased risk,

(d) consistent results when replicated in different settings,

(e) a plausible explanation

Sensitivity and specificity

Every diagnostic test involves a trade-off between sensitivity and specificity. Sensitivity is increased at the expense
of specificity when the cutoff is lowered.

 Sensitivity (epidemiology) (true positive rate)

 The proportion of individuals that correctly register as positive in a clinical test designed to identify a
disease

 A test with a high sensitivity will yield a low false negative rate.

 A test with a high sensitivity (i.e., few false negatives) but low specificity for a disease with
low prevalence will yield a high false positive rate.

 Can be used for screening purposes

 See two-by-two table below for the formula.

 Specificity (true negative rate)

 The proportion of individuals without a disease that correctly test negative in a clinical test designed
to identify that disease: i.e., true negative results divided by total true negative and false
positive results (typically expressed as a percentage)

 A highly specific test will yield a low false positive rate

 Can be used to confirm the diagnosis following a positive screening test

 See two-by-two table below for the formula.

Raising the cutoff of a test (eg increasing the inclusion criteria) will increase the specificity and decrease the sensitivity.

Predictive values

 Positive predictive value (PPV)

 The proportion of individuals who test positive for a disease that actually have that disease

 On the other hand, the probability that an individual who tested positive actually does not
have the disease is calculated as follows: 1- positive predictive value

 The positive predictive value increases with increasing prevalence of disease in the population.

 See two-by-two table below for the formula.

 Negative predictive value (NPV)

 The probability that an individual who tested negative is actually disease-free

 On the other hand, the probability that an individual who tested negative actually has the
disease is calculated as follows: 1 - negative predictive value

 The negative predictive value decreases with increasing prevalence of the disease in the population.

 See two-by-two table below for the formula.

 Likelihood ratio
  Determines the utility of a diagnostic test in clinical practice; likelihood ratio is not influenced by
disease prevalence

 Reflects how much more likely the disease is in a person with a positive (positive likelihood ratio) or
negative (negative likelihood ratio) test result compared to the pretest probability.

 If the likelihood ratio is > 1, then it is associated with the disease.

 If the ratio is < 1, then it is associated with absence of the disease.

 If the likelihood ratio is 1, then the post-test probability is similar to the pretest probability,
and therefore the test has poor clinical utility.

 Positive likelihood ratio

 Ratio of the sensitivity rate (true positive rate) to the false positiverate

 Sensitivity/(1 - specificity)

 Negative likelihood ratio

 Ratio between the false negative rate and the specificity (true negative rate)

 (1-sensitivity)/specificity

 Pre-test probability

 The probability that a patient with a particular manifestation has a specific disease before the result
of the diagnostic test is known

 The pretest probability of a disease is reflected by its prevalence in a particular region

 Negative and positive predictive values depend on the test subject's pretest probability of disease
(unlike sensitivity and specificity)

 A higher pretest probability will decrease the NPV and increase the PPV of a test

 A lower pretest probability will increase the NPV and decrease the PPV of a test

 Cutoff values

 Every diagnostic test involves a trade-off between sensitivity and specificity.

 In a ROC curve, for example, the sensitivity is plotted against specificity for different cutoff
values and ideally, the cutoff point is on a curve in the upper left corner, where sensitivity
and specificity are 100%

 Sensitivity, specificity, positive predictive values, and negative predictive values vary according to the
criterion or cutoff values of data

 What happens when a cutoff value is raised or lowered depends on whether a diagnostic test requires
a high value (e.g., tumor marker for cancer, lipase for pancreatitis) or a low value
(e.g., hyponatremia, agranulocytosis)
  Lowering or raising a cutoff value for a high value test

 ↓ cutoff value (i.e., broadening the inclusion criteria): lower specificity, higher
sensitivity, lower positive predictive value, higher negative predictive value

 ↑ cutoff value (i.e., narrowing the inclusion criteria): higher specificity, lower
sensitivity, higher positive predictive value, lower negative predictive value

 Lowering or raising a cutoff value for a low value test (causes opposite results)

 ↓ cutoff value (i.e., narrowing the inclusion criteria): higher specificity, lower
sensitivity, higher positive predictive value(decrease in false positive > decrease
in true positives), lower negative predictive value (increase in false negatives >
increase in true negatives)

 ↑ cutoff value (i.e., broadening the inclusion criteria): lower specificity, higher
sensitivity, lower positive predictive value(increase in true positives > increase
in false positives), higher negative predictive value (decrease in false negatives >
decrease in true negatives)

Unlike sensitivity and specificity, which rely solely on the diagnostic test itself, predictive values are also influenced by
disease prevalence!

Verifying the presence or absence of a disease

 Screening test

 Used to identify disease in asymptomatic individuals.

 E.g., mammogram for breast cancer or a Pap smear for cervical cancer

 Should have a high sensitivity

 Confirmatory test

 Confirms disease in individuals with signs or symptoms of disease

 E.g., biopsy for breast cancer or cervical cancer

 Usually performed after a screening test to confirm a diagnosis

 Should have a high specificity

Receiving operating characteristic curve (ROC curve)

 A graph that compares the sensitivity and specificity of a diagnostic test

 Used to show the trade-off between clinical sensitivity and specificity for every possible cutoff value to
evaluate the ability of the test to adequately diagnose subjects (e.g., diseased vs. nondiseased)

 The y-axis represents the sensitivity (i.e., true positive rate) and thex-axis corresponds to 1 -
specificity (i.e., false positive rate).

 A test is considered more accurate if the curve follows the y-axis.

  A test is considered less accurate if the curve is closer to the diagonal.

 The area under the curve also allows the usefulness of tests to be compared: The larger the area under
the ROC curve, the higher the validity of the test.

Two-by-two table

 Definition: a type of contingency table that displays the frequency of two categorical variables, often exposure
and outcome of disease

Disease No disease Total Interpretation

Positive test  True positive  False positive  All individuals  Positive

result (TP) (FP) with positive predictive
test results value = TP/(TP
(TP + FP) + FP)

Negative test  False negative  True negative  All individuals  Negative

result (FN) (TN) with negative predictive
test results value = TN/(FN
(FN + TN) + TN)

Total  All individuals  All individuals  All individuals

with disease without (TP + FP + FN
(TP + FN) disease + TN)
(FP + TN)

Interpretatio  Sensitivity  Specificity (true

n (true positive negative
rate) = TP/(TP rate) = TN/(FP
+ FN) + TN)

 False negative  False positive

rate rate
= FN/(TP + FN = FP/(FP + TN)
)

Example of a two-by-two table

Diagnostic test for tuberculosis (TB)

(The table below is an annotated 2x2 table, with additional columns detailing total amounts and their interpretation.)
 Patients with TB Patients without TB Total

Positive test result 800 (true positive) = TP 400 (false positive) = FP 1200

Negative test result 200 (false negative) = FN 3600 (true negative) = TN 3800

Total 1000 (TP + FN) 4000 (FP + TN) 5000

 Sensitivity (true positive rate) = TP/(TP + FN)

 800/(800 + 200) = 80%

 Specificity (true negative rate) = TN/(FP + TN)

 3600/(400 + 3600) = 90%

 False positive rate = FP/(FP + TN)

 400/(400 + 3600) = 10%

 False negative rate = FN/(TP + FN)

 200/(800 + 200) = 20%

 Patients who have a negative test result despite actually having the disease (ie those who are
incorrectly labelled as healthy or without disease).

 When the cutoff level of a Dx test is raised, the FN will consequently increase.

 Positive predictive value= TP/(TP + FP)

 800/(800 + 400) = 66.6̅. %

Core ethical principles

Medical ethics is founded on a set of core principles.

 Autonomy

 Respect patients as individuals (e.g., respecting their privacy by maintaining confidentiality and being
truthful about their medical care).

 Provide the information and opportunity for patients to make their own decisions regarding their
care (e.g., informed consent).

 Honor and respect patients' decisions regarding their choice to accept or decline care.

 In addition to having the right to refuse a diagnostic or therapeutic intervention, patients

also have the right to refuse to receive information

 Beneficence

 Act in the best interest of the patient and advocate for the patient.

 May conflict with autonomy

 Nonmaleficence
  Avoid causing injury or suffering to patients

 May conflict with beneficence

 Justice

 Treat patients fairly and equitably.

 Equity is not the same as equality.

Obligation to treat

 A physician is obligated to treat patients in a medical emergency in which failing to provide treatment would
immediately endanger the patient's life.

 According to the Emergency Medical Treatment and Labor Act(EMTALA), any hospital with an
emergency department is required to screen for emergency medical conditions if requested and, if
such a condition exists, provide treatment until that condition is stabilized.

 Physicians are not obliged to treat a patient longitudinally and may end a doctor-patient relationship if they
wish, as long as the patient or their surrogate decision maker is notified and has the ability (e.g., time, money)
to establish care with another physician. The physician is also obligated to facilitate the transfer of care.

 Freedom to treat: Freedom to treat describes a legal legitimization, in which each person (independent of
educational level) is permitted to perform medical treatments. Since the Freedom to Treat Act was abolished in
1939, only physicians and certain authorized persons (e.g., natural health professional) are allowed to treat
patients.

Decision-making capacity and legal competence

Decision-making capacity

 Definition: the psychological and/or legally capability to process information, make decisions, and understand
the consequencesof the same with regard to health care

 Typically determined by the attending physician

 In order to have capacity, a patient must have:

 Understanding: the patient's ability to understand the meaning of information provided by the
physician

 Appreciation: the patient's ability to determine how facts are relevant to their situation

 Reasoning: the patient's ability to use the information provided by the physician to make decisions
regarding their care

 The ability to express a choice: the patient should have the ability to clearly communicate their
choice of treatment

Legal competence
  Definition: legal assessment of a patient's ability to make decisions

 Assessed by a court of law (physicians do not have the legal power to pronounce patients legally incompetent)

 Questions of legal competence arise in the presence of reduced mental capacity (e.g., severe mental illness,
intoxication, impulsive/constantly changing decisions, or decisions that are inconsistent with the patient's
values)

Shared decision-making

 A model in which patients and physicians decide on the best treatment option together

 Empowers patient, as it is based on the patient's personal values, cultural beliefs, and preferences

 Results in better health outcomes and increases patient satisfaction

Surrogate decision-making

 When a patient lacks decision-making capacity or competence, another person must make treatment decisions
for them.

 The surrogate decision-maker may be appointed by patients(e.g., medical power of attorney), legally
appointed (e.g., court-ordered guardian), or next of kin (if no advance directive exists).

 The exact hierarchy of decision-making varies from state to state. However, it generally follows the
following order:

1. A mentally competent patient capable of expressing his/her own decision

2. Advance healthcare directive

 Durable medical power of attorney: a document through which an individual

designates a surrogate health care decision-maker in the event that he/she
lacks decision-making capacity or competence

 Living will

 Should the durable medical POA and the living will be in conflict, the POA
can override the living will only if such a decision is in line with the
patient's most recently expressed wishes.

3. Next of kin

 Spouse

 Adult child

 Parent

 Adult sibling

 In about half of states: “close friend”

4. Ethics committee or legal consult

  Regardless of who the surrogate is, it is paramount that decisions be made based on what patients themselves
would have wanted.

 The decision-maker should not let their own preferences influence decision-making.

 A patient may have expressed their wishes via:

 Oral advance directive: an incapacitated patient's prior oral statements regarding their
preferences

 Living will (written advance directive): a legal document in which patients describe their
wishes regarding their healthcare (e.g., to maintain, withhold, or withdraw life-
sustaining care), should they become incapacitated

 If the patient's wish cannot be determined and there is a disagreement regarding the course of
action:

 It is prudent to convene a meeting between the disagreeing parties in order to facilitate a

conversation about what the patient would have desired.

 If the patient's most recent wish still cannot be determined, the wishes of the
appropriate surrogate decision makershould ultimately be followed.

LED TO REASON: Lead in , Explore , Diagnosis , Treatment , Options , Results , Eventualities , Sound mind , Open
questions , Notes

Patient with decision-making capacity and competence (even, e.g., psychiatric patients) have the right to provide or
withdraw informed consent at any time (even during a procedure)!

Disclosure

Full disclosure

 Patients have the right to full medical disclosure

 A family does not have the right to ask a physician to withhold information from a patient with decision-
making capacity and competence without good reason

 Exceptions:

 If the patient requests that the physician withholds information

 Therapeutic privilege: a physician determines that full disclosure would cause severe harm to the
patient's severe psychological harm (e.g., following an unfavorable prognosis)

Medical errors

 Regardless of the outcome of a treatment, a physician must inform the patient immediately if an error has
occurred and disclose the nature of that error.

 There are several elements of an optimal error disclosure

 Clearly admit an error has occured

  State the course of events leading to and during the error, avoiding jargon

 Explain the consequences of the error, both immediate and long term (if necessary)

 Describe corrective steps and future preventative steps

 Express personal regret and apology

 Allow ample time for questions and continued dialogue

 If a physician believes that a colleague has committed an error in a patient's care, the physician should urge
their colleague to report this error to the patient.

 If the colleague refuses, the physician should report this error via their hospital's or clinic's standard protocol.

 If the cause of an error is not immediately known, the physician should inform the patient and maintain
contact while investigations are being carried out.

Research disclosure

 Patients must receive full disclosure prior to enrollment in a clinical trial

 All aspects of the experimental protocol (i.e., the purpose of the study, the study design)

 Any potential conflicts of interest

 Any foreseeable hazards to the patient

 The likelihood of direct benefit to the patient

 All alternative treatment options

 medical strategy, treatment, or device is safe

 The differences between physician responsibility in the role of researcher and in that of attending
physician

 A physician-researcher is primarily concerned with clinical data and medical innovation

 A treating physician is primarily concerned with the treatment and best interests of the
patient

 An informed consent form, approved by the responsible research institutional review board, must be
completed by the patient prior to initiation of treatment

 Patients participating in clinical research have the right to withdraw from a clinical trial at any time, for any
reason (as with any form of informed consent)

Under the Health Insurance Portability and Accountability Act(HIPAA), patients have a legal right to obtain copies of their
medical records within a specified timeframe!

End-of-life issues
End-of-life care

 There is a number of ethical dilemmas may arise in context of end-of-life care.

 The physician's role in ethical dilemmas is to facilitate communication (e.g., family meetings) and to reiterate
the importance of focusing on what patients themselves would have preferred.

Physician-aided death

 Physician-assisted suicide

 When a physician supplies a patient with the means to end their own life (e.g., a physician provides a
patient with a lethal doseof morphine that the patient then self-injects)

 Illegal in most states

 Euthanasia

 The active termination of a terminally ill patient's life by a physician to end suffering. (e.g., a
physician injects a lethal dose of morphine).

 Euthansia is illegal in the United States.

 Terminal sedation

 It is legal to adjust medical therapy accordingly to provide relief from pain and suffering in a patient
with terminal illness, despite hastening the patient's dying process (e.g., increasing doses
of morphine in a patient with metastatic cancer)

 Legal and distinct from euthanasia in so far as the intent must be to relieve pain rather than bring
about death, even though it may hasten the dying process.

 Not an appropriate means of addressing primarily existential suffering, e.g., death anxiety.

 Principle of double effect: An ethical principle that legitimizes an act of good intent despite causing
serious harm (e.g. self defense homicide or terminal sedation).

Do not resuscitate orders (DNR orders)

 Only refers to withholding cardiopulmonary resuscitation

Withdrawal of care

 Patients with capacity (or their surrogate decision-makers) have the right to refuse any form of treatment at
any time, even if that would result in that patient's death.

 Physicians should make an effort to understand the reasons behind the patient's decision for refusing
treatment.

 There is no ethical difference between withholding care and withdrawing care at a later time

Futile treatment
  A physician is not ethically obligated to provide treatment if it is considered futile (inappropriate treatment),
even if requested by the patient or surrogate.

 Treatment can be considered futile if:

 There is no evidence for the effectiveness of treatment

 If the intervention has previously failed

 If last-line therapy is failing

 If treatment will not fulfill the goals of care

Organ and tissue donation

 Deceased donors

 Patients may declare themselves organ and tissue donors prior to death (e.g., in a living will or
driver's license)

 Hospitals that receive payment from Medicare must discuss organ donation with the family of the
deceased

 Patients (e.g., in a living will) or their families may specify which organs may be donated after death

 Hospitals must decline organs that are considered unsuitable:

 Sepsis

 HIV

 Poor organ function (e.g., patient died of acute renal failure, so kidneys would be refused)

 Hypothermia

 Patient > 80 years old

 Prolonged organ ischemia (e.g., patient found deceased at home)

 Living donors

 Nonvital organs and tissues can be acquired from living donors (e.g., liver or bone marrow)

 Prior to donation, donors must give full informed consent

 Donors have the right to withdraw from donation at any time

 Donors may select the recipient of their donation

 Donors may not be paid for their donation, but can be reimbursed for associated costs (travel, food,
lost wages, etc.)

 A donor may engage in an “organ swap”

Death

 Criteria: Death can be diagnosed if a patient meets criteria for brain death or cardiopulmonary death. Only one
of these conditions is required, although they may coexist.

 Brain death

 Irreversible, complete loss of function of the entire brain (including the brainstem), even if
cardiopulmonary functions can be upheld by artificial life support

 See section on testing for brain death in “Elevated intracranial pressure and brain herniation”

 Cardiopulmonary death: the absence of a spontaneous heartbeat in an asystolic patient.

A hypothermic patient must be warmed to normal body temperature before death can be diagnosed!

Confidentiality

 A physician is ethically and legally obliged to keep a patient's medical information (including information
disclosed by the patient to the doctor) confidential, with the following exceptions:

 The patient directly requests the physician to share information with another party (e.g., a family
member or for insurance purposes)

 The Health Insurance Portability and Accountability Actrequires verbal or written consent
before releasing medical information

 Individual hospitals or physician practices may have additional policies to verify the identity
of the receiver (e.g., via phone call) before sharing information

 The patient has a notifiable disease

 In this case, a physician is legally permitted to notify only a public health official. Depending
on the disease, the patient should be encouraged to inform any third parties that may have
been infected (e.g., sexual partners). The physician does not, however, have the right to
inform third parties without the patient's consent.

 The patient poses a danger to others (e.g., impaired driver, homicidal)

 Physicians should protect the intended victim of homicide by any reasonable means (e.g.,
notify the police)

 The patient poses a threat to himself or herself

 Elder abuse and child maltreatment

 The patient has suffered penetrating trauma from assault (e.g., a gunshot wound, stab wound)

 The patient is a minor and care does not involve sexual or addiction medicine (see informed consent
in minors)
  Confidential information should only be shared with other health care workers if they are immediately
involved in the patient's care.

 Any other requests by health care workers to share information should be denied

 Avoid discussing patient information in public areas.

Societal factors

Notification of diseases

 The diagnosis of several infectious diseases must be reported to public health officials. Reportable
diseases vary from state-to-state, but some examples include:

 HIV

 Sexually transmitted infections (e.g., gonorrhea, chlamydia)

 Hepatitis

 Tuberculosis

 Rabies

 Meningococcal meningitis

 Some forms of food poisoning (e.g., salmonellosis)

 Patients must be informed that their disease is reportable, and they should be encouraged to inform any
recent contacts at risk of infection.

 The public health department is responsible for notifying third parties if the patient refuses to inform them

Elder abuse and child abuse

 Elder abuse/neglect

 Any form of physical, psychological, or financial mistreatment of an elderly person (exact age varies
by jurisdiction). Signs of this include:

 Uncommon fractures

 Malnutrition

 Dehydration

 Anogenital injury

 Unexplained cuts, bruises, pressure ulcers, burns

 Depression/suicidality

 Unusual loss of property/money

  Always perpetrated by someone with a longitudinal relationship and responsibility for the patient
(e.g., a caregiver or relative)

 Physicians are legally (and ethically) obliged to report suspected elder abuse

 Child maltreatment

 The precise legal definition of child abuse and neglect varies by state, but broadly can be defined as
any act (or failure to act) that produces an imminent risk of serious harm to an individual < 18 years
old

 Physicians are legally (and ethically) obliged to report suspected child abuse

Domestic violence

 Refers to any form of actual or threatened physical or emotional harm within a household, frequently used to
by one person to maintain power over another.

 Usually occurs between partners in a relationship, in which case it is more accurately called intimate partner
violence

 When a physician suspects domestic violence, they should privately speak with the affected patient, inquire
further, and offer assistance.

 Physicians are not legally permitted to report domestic violencewithout patient consent (unless the patient is
incompetent e.g., mentally disabled, elderly, or a minor)

 In cases where the patient refuses aid, a physician should reiterate their support of the patient and the
availability of aid at any time.

Driving restriction

 Physicians are sometimes required to report patients who are considered unsafe to drive (e.g.,
uncontrolled epilepsy is one of the most common reasons) to the licensing authority.

 A physician should always suggest another means of transportation

 Generally, only patients at a high risk of having a seizure while driving should be restricted

 Frequent, poorly-controlled seizures

 Recent history of seizures

Prisoner execution

 It is not ethical for physicians to participate in any executions, regardless of state laws that enforce the death
penalty.

Physician-patient romantic relationships

 Romantic relationships with current patients are always unethical and inappropriate

 A romantic relationship compromises the objectivity of the physician's decisions in regards to the
care of that patient
  Such relationships make patients more vulnerable to exploitation

 Romantic relationships with former patients are also inappropriate if:

 The physician has a position of influence from his/her previous professional experience with the
former patient (e.g., details of emotions expressed in previous interactions with the patient)

 Less than one year has passed since the end of the patient-physician relationship

 Should a physician feel that their actions may be perceived as sexual and/or lead to a romantic relationship
with a current patient, the physician should take active measures to avoid unnecessary contact with the patient

 Use direct, close-ended questions

 Interview with a chaperone present

Torture

 A physician should act in the best interest of their patient, and provide all possible support to aid the patient
and facilitate removal from harm, including:

 Refusing to participate in torture

 Ensuring the patient's safety

Abortion and stillbirth laws

 Stillbirth: an autopsy of the fetus and placenta should be performed (with permission from the parents if the
parent is a minor) after a confirmed and unexplained stillbirth

 Abortion

 Abortion laws vary greatly between US states

 Most states only permit a licensed physician to perform abortions:

 If the mother's life or health is at risk because of the pregnancy

 Up to a certain gestational age

 Most states allow physicians to refuse performing abortions under the condition that patients are
referred to another physician who is skilled and willing to perform abortions

 Patient counseling prior to abortion procedures is mandatory in some states

 Most states require that parent's of minors undergoing an abortion procedure are notified and/or
informed to provide consent

Malpractice

 A civil suit because of negligence is due to substandard care by a physician

 Medical negligence leads to patient harm

Informed consent
Definition

 The process of briefing a patient (or a surrogate decision-maker) about their medical condition and treatment
options, then obtaining consent to pursue a selected course of treatment.

 Patients (or their surrogate) must demonstrate decision-makingcapacity and competence before they can
consent to, or refuse surgery (e.g., if patients make decisions contrary to sound medical reasoning such as
refusing blood transfusions out of religious conviction).

Language

 Discuss health care decisions with patients in terms they can relate to

 Communicate in a language that the patient understands

Timepoint of patient briefing

 The patient must be informed in time (with a sufficient interval) prior to an elective medical procedure

Extent of patient briefing

A patient should be educated about their diagnosis, treatment options, and the risks and benefits of those options
before treatment.

 Diagnosis and natural course of the disease without any treatment

 Nature of the proposed medical or surgical treatment

 Benefits

 Known complications, estimated risks of death and morbidity

 Types and risks of anesthesia, if necessary

 Alternative treatments

 Informing the patient about the possibility of intraoperative findings that may require more intervention than
originally planned.

 Medical safety advisory: The physician is obliged to brief the patient about the measures necessary for
assuring treatment success (e.g., physical rest after surgery).

Expressing a decision

 After patients reviews the standardized information sheet, they are briefed by the physician over the course of
the planned intervention and all relevant risks and complications.

 Once patients (or their surrogate decision-maker) have been briefed, they must be provided with adequate
time to digest that information.

 The patient (or their surrogate decision-maker) must then clearly communicate their decision

Assessment of decision making capacity

Criterion Patient risk
Communicates a choice Patient able to clearly indicate preferred treatment option
Understands information provided Patient understand condition and treatment options
Appreciates consequences Patient acknowledges having the condition and likely
consequences of treatment options, including no
treatment
Rationale given for decision Patient able to weight risks and benefits and offers
reasons for decision

-having a psych diagnosis, in or itself should not be a determining factor in capacity assessments. Patients with a
history of psych illness should be carefully assessed to determine if acute symptoms are directly impairing their ability
to reason (eg a patient who has severe delusions related to medical condition, disorganization, or cognitive impairment
may lack capacity and require a surrogate decision maker.

-right to refusal includes emergency procedures

Exceptions to standard informed consent

 The following measures are generally performed without (or against) the patient's consent, although a
thorough attempt to persuade the patient to comply voluntarily is preferred:

 Life-threatening emergencies (e.g., an unconscious trauma patient without a surrogate decision-

maker present)

 The physician can be individually accountable for unequivocally necessary measures in

an acute emergency.

 If the patient is unconscious, the patient's presumed will is determined, with a particular
gravity assigned to the advance directive.

 A patient lacking decision-making capacity, but whose surrogate decision-maker has authorized
intervention

 A patient lacking decision-making capacity, for whom no surrogate decision-maker is available, and
treatment is in the best interest of the patient

 Examination, treatment, or quarantine to prevent epidemics

 If the patient's decision to refuse treatment poses a safety risk to their own well-being and/or the
welfare of others(e.g., in the event of severe psychosis, patient with active TB)

 A legal form must be completed by a physician that allows temporary commitment (usually
for a few days at most)

 Informed consent of the patient or surrogate is required if hospitalization is required

beyond the stabilization period

Informed consent in minors

 A minor is any person < 18 years old in most states. Exceptions include:

 Mississippi: < 21 years

  Nebraska and Alabama: < 19 years

 Parental consent is required before a minor receives medical care, with a few exceptions:

 The hospitalization or treatment is emergent and life-saving(e.g., trauma, suicidal ideation)

 The minor is legally emancipated

 The minor is seeking care regarding sex (contraception, pregnancy care, or STIs) or addiction care

 If the parents of the patient are themselves minors, the grandparents may give consent for their
grandchildren.

 Even in these situations, the minor should be encouraged to discuss their issues with their parents.

 If parents refuse consent to treatment of a child for a non-emergent but fatal medical condition (e.g.,
bacterial meningitis, malignancy), the physician should first discuss this decision with the parents, then seek a
court order mandating treatment if parents continue to refuse.

 A parent cannot refuse an emergently life-saving intervention for a minor (e.g., blood transfusion for
hemorrhage), not even for religious reasons

Informed consent during pregnancy

 A pregnant woman has the right to refuse health care even if her decision poses a risk to the unborn fetus.

Obtaining patient consent is crucial because, without it, any medical procedure can represent an attempt to initiate
harmful or offensive contact with a person, or threat to do so.

Difficulties in obtaining consent should not delay life-saving procedures!

LED TO REASON: Lead in, Explore, Diagnosis, Treatment, Options, Results, Eventualities, Sound mind, Open
questions, Notes

Conflicts of interest

 A conflict of interest occurs when a physician's objectivity regarding their primary interest (e.g., patient
welfare) is potentially affected by a secondary interest (e.g., personal financial gain).

 Patients may offer gifts to a physician for a variety of reasons.

 Not accept gifts of inappropriately high value

A physician must disclose all conflicts of interest to all affected parties and refer affected patients to an unbiased
colleague whenever possible.

Examples of ethically challenging situations

Autonomy

 An adult patient refuses treatment based on religious belief:

  Explain the treatment option and other available alternatives

 Make sure that the patient understands the consequences

 Respect patient's choice

 Patient wants to try alternative medicine

 Identify the underlying reason behind the decision

 Do not negate or devalue patient's idea (will affect patient-physician relationship)

 Evaluate for drug interaction, adverse effect, safety; allow treatment integration if it is safe

Abuse

 Patient discloses abuse by close partner

 Evaluate safety and the presence of emergency plan

 Show empathy and willingness to provide continuous support

 Counsel and evaluate for comorbid psychological issues

 Perform thorough documentation as the victim might want to take legal measures

 Do not force the patient to leave the partner

 A pediatric patient has injury inconsistent with caregiver's report

 Physicians are obliged by law to report cases of child abuse

 Inform authorities and keep the child in a safe place

Confidentiality

The obligation to maintain confidentiality prohibits the physician from disclosing information about the patient’s
diagnosis or treatment to anyone not directly involved in, or necessary to, the patient’s management. Physicians should
avoid discussing a patient’s medical condition in public areas where comments might be overheard.

 Family members request information about patient's health condition: do not discuss issues with relatives
without the consent of the patient

 Family members request the physician to withhold information about the diagnosis of the patient (e.g., patient
is diagnosed with lung cancer)

 Understand why the family members want to withhold this information (helps to build an empathetic
relationship, addresses fear and anxiety)

 Evaluate the extent of information the patient wants to receive

 Deliver information based on the patient's preference

  Patient with HIV refuses to inform his/her partner

 Counsel the patient to disclose the information to individuals at risk

 If the patient refuses, inform the health department for tracing at risk individuals

 At risk individuals can be informed by the physician or the health department

 There is no legal consequence for breaching confidentiality

Competence and decision making

 Parents refuse lifesaving treatment for their child

 Emergency treatment: go ahead and treat

 Non-emergency essential treatment: get court order

 A 16-year-old pregnant teenager wants to have an abortion

 Many states require parental consent for an abortion in minors

 A 15-yearl-old teenager wants to keep her baby against her parent's will

 The patient has the right to decide about her baby's fate (adoption or keeping the baby)

 Provide practical information about all options

 Support the patient irrespective of her decision

 A 14-year-old girl request for contraceptive

 Advise on safe sex practices and prescribe contraceptive

 No need to notify parents to get a consent

 Patient is suicidal or homicidal

 Considered to have impaired judgement

 Assess the threat (organized plan, access to weapons)

 Admit patient voluntarily; admit involuntarily if patient refuses

 In homicide threats: inform authorities and threatened individual

Malpractice

 Patient receives wrong treatment/ test: Inform the patient even if no harm has been inflicted and apologize.

Miscellaneous cases

 Angry patient (e.g., waiting at the office for a long time):apologize, acknowledge anger, refrain from justifying
or explaining the delay.
 Patient desires an unnecessary intervention (e.g., diagnostic or therapeutic procedure, unnecessary
medication)

 Find out why the patient wants the intervention and address any underlying concerns.

 Avoid performing unnecessary medical or surgical interventions.

 Do not refuse to see the patient or refer the patient to another physician.

 Patient has poor adherence or difficulty of taking medications

 Identify the underlying causes of non-adherence.

 Take a non-judgemental stance and use motivational interviewing if possible.

 Evaluate willingness to change.

 Describe treatment plan in easily understandable language, give written instructions, use teach-back
method, and involve other relatives with the permission of the patient.

 Do not refer the patient to another physician.

 Physician is impaired in work environment (e.g., due to substance use)

 As the physician is a threat to the safety of his patients, he should be reported to a supervisory
entity.

 The supervisory entity handling impaired physician and monitors their license is the Physician Health
Program (PHP).

 If PHP measures fail, the state licensing board needs to be informed.