The anatomy and physiology of clinical research part 2

Question 1

Background significance

Answer 1

This section sets the proposed study into context and gives its rationale.

In published scientific articles, the “introduction” section is first read by many readers to tell them “where the article is going and why”.

This section cites previous research that is relevant and indicates the problems with the prior research and what uncertainties remains.

It will specify how the findings of the proposed protocol will help resolve these uncertainties and lead to new scientific knowledge.

Question 2

Move structure 3 step process

Answer 2

Introduce a research area (general)
identify the gap
fill the gap (specific)

Question 3

Study design

Answer 3

Whenever a study is being planned or designed, researcher cannot:

• Manipulate the independent variables.
• Examine the cause and effect between two variables.

HOWEVER, it is possible to examine the associations between the independent (predictor) and dependent (outcome) variables in a study.

Question 4

Clinical Studies are observational studies that considers an association between two variables

Answer 4

The researcher does not manipulate the independent variable(s).

This is not to say that it is impossible to do so, but it will be impractical or unethical to do so. It is not possible to examine the cause and effect between the variables, but we can examine the associations or relationship between the predictor/independent and outcome/dependent variables

Association = connection

Question 5

Observational studies

Answer 5

Considering an association between two variables

Question 6

How study design is split

Answer 6

It is split into clinical trials and clinical studies
Clinical studies is split into cross sectional studies, cohort studies and case control studies

Clinical trials is split into phases 1,2,3,4

Question 7

Cohort studies

Answer 7

For example, a researcher may be interested in the effect of illegal, recreational drug use (the independent variable(s)) on certain types of behavior (the dependent variable(s)). However, whilst possible, it would be unethical to ask individuals to take illegal drugs in order to study what effect this had on certain behaviors. As such, a researcher could ask both drug and non-drug users to complete a questionnaire that had been constructed to indicate the extent to which they exhibited certain behaviors

Predictor (independent variable) - the effects of illegal, recreational drug use
Outcome (dependent variable) - people with a certain type of behavior

It is unethical to ask the subjects to take the illegal drugs for the researchers to investigate the drugs’ effects on their behaviour especially those who are unwilling.

However, a researcher can create a questionnaire for both drug and non-drug users to fill in to indicate the extent to which they exhibit certain behaviours.

Question 8

Case control study / retrospective study

Answer 8

Compares patients who have the disease or outcome of interest (cases) with patients who do not have the disease or outcome (control) from the same population.

Question 9

Cases definition

Answer 9

cases - patients who already have the disease or outcome
control - patients who do not have the disease or outcome

The main objective is to determine the exposure to risk factor of interest from both the cases and control group

Question 10

example of retrospective study:
There is a suspicion that ZnO found in sunscreens worn by lifeguards is more effective at preventing sunburns that lead to skin cancer than other sunscreens.
We want to investigate if sunscreen containing ZnO is a more effective in the prevention of skin cancers

Answer 10

cases - a group of former lifeguards that had developed cancer on their cheeks and noses was
compared to
control - a group of lifeguards without this type of cancer

the lifeguards were also assessed on their prior exposure to ZnO and other sunscreens without ZnO

Question 11

Characteristics of Retrospective study

Answer 11

Want to look back at the history of each of the persons to compare how frequent they had been exposed to mentioned risk factor in order to determine the relationship between the risk factor and disease.

No intervention is attempted

No attempt is made to alter the course of the disease

Require the subjects to recall information which could be very difficult

Goal is to determine the exposure to the risk factor of interest from each of the two groups – cases and controls

Question 12

The controls must match similarly to cases to ensure other variables do not affect the results

Answer 12

in this case, same age, similar number of seasons as life guard, amount of time per season etc.

Question 13

Case control studies: Persistent pulmonary hypertension of the newborn (PPHN)

Answer 13

Persistent pulmonary hypertension of the newborn is associated with substantial infant mortality and morbidity

There might be an association between the PPHN disease and the use of selective serotonin reuptake inhibitor Fluoxetine late in the 3rd trimester of pregnancy.

Perform a case control study to assess whether PPHN is associated with exposure to SSRIs during late pregnancy

Question 14

Case control studies

Answer 14

Studies are applied as investigators are looking at whether a suspected exposure contributed to the outcomes in patients

compare 2 groups of people, one with disease (cases), and another similar group of people who do not have the disease or condition (controls)

Question 15

Cohort studies (may be retrospective and prospective)

Answer 15

One or more samples (usually a large number) are followed over time.

Determine if a participant’s exposure (risk factor) is associated with disease/outcome

Question 16

Retrospective studies

Answer 16

Examine information and specimens that have been collected from the past

Question 17

Prospective studies

Answer 17

Studies that begin in the present and follow subjects into the future

Subjects who develop the disease over time is recorded

Question 18

Cross sectional studies/prevalence studies

Answer 18

Disease and exposure are measured simultaneously in a given population. This is also known as prevalence studies.
Provides a “SNAPSHOT” of the frequency and characteristics of a disease in a population at a particular point in time.
Measure the prevalence of exposure with prevalence of disease/outcome.
Cross Sectional Studies provide useful information for planning health services and results can usually be obtained quickly.

Question 19

Advantages of cross sectional studies

Answer 19

These studies are easy to conduct and relatively cheap
– does not require follow up

Allow researchers to compare many different variables at the same time

Question 20

Disadvantage of cross sectional studies

Answer 20

Not possible to determine the direction of the association, i.e. not known if the exposure preceded the disease and is therefore a potential cause of disease
example: cant tell whether having cats is linked to being poor or having no cats is linked to being rich

Aim to provide data on the entire population under study unlike case control studies which include individuals with a specific characteristics

Question 21

Aim of cross sectional studies

Answer 21

Aim to provide data on the entire population under study unlike case control studies which include only individuals with a specific characteristic

Question 22

Purpose of Clinical trials

Answer 22

Examine the EFFECT of an INTERVENTION & allows the investigator to observe the EFFECT(S) on the OUTCOME VARIABLE. Often appear at a very late stage of the study

2 main purposes

• Assessment of the efficacy and/ or safety of a drug/treatment
• Comparing the efficacy, safety, risk benefit, relationship or utility of 2 treatments

Question 23

Cross sectional studies vs cohort studies vs case control studies

Answer 23

Cross-sectional studies only provides a snapshot of the frequency and characteristics of a disease in a population at a particular point of time.

Cohort studies follows a group of people through time (usually years) and record which individuals develop the outcome of interest.

If comparing the wheat consumption of children who have celiac disease and without celiac disease before their first birthday, case control studies are appropriate for this study.

Question 24

example of cohort study, assess the impact of sun exposure to skin damage in dragon boaters.

Answer 24

Some team members applied sunscreens and some did not.
at the end of practice, the dragon boater skin was analyzed for texture, sun damage and burns

Comparison of skin damage were then made based on the use of sun screen

Question 25

example of cohort study, determine if there is a strong link between working for pay and adolescent use of tabacco

Answer 25

A group of African American first-grade students in Baltimore were followed since the first grade.
In this study, the number of hours these kids worked per week were monitored.

It was found that those that had worked for more than 10 hours per week had initiated use of tobacco earlier.
There is a strong link between working for pay and adolescent tobacco use.
Policymakers should monitor the conditions under which young people work to help minimize young workers’ tobacco use and potential for initiating use

Question 26

example of cross sectional study: obesity and television watching

Answer 26

Obesity and television watching

A sample of people from the population may be polled and asked about how their BMI and the number of hours of television the person watches each day

This study aimed to provide insight on whether obesity and television watching are associated.

However, it does not help to determine which might cause the other. Example, it is not known if obesity causes more television watching or if more television causes obesity

Question 27

Example of clinical trial

Answer 27

In pediatric population, primary CNS malignancies are the most common solid organ tumour totaling approximately 20% of cancers in children age 1 – 4 years and approximately 30% in children ages 5 – 9 years.

Supratentorial tumours constitute 31% of pediatric CNS tumours.

Although post operative radiotherapy has been shown to improve survival in patients with high grade supratentorial astrocytoma, the optimum radiation dose has not been established.

Currently for radiotherapy, patients receive either 45 Gy or 60 Gy.

What would be your objective?
- the main objective of the study was to assess whether the higher dose would improve lifespan
How would you conduct this clinical trial
- compare the mean survival time of patients with the tumors who has been received 45gy or 60gy radiotherapy in past operative treatment

Question 28

Summary of part 2

Answer 28

How is the background & significance constructed in a clinical research?

What are the different components of clinical studies in a study design? How are they used in a clinical research?

What are clinical trials? How are they conducted in a clinical research?