(3) designing a study i

7/30/2019 (3) Designing a Study I

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Rapid Review:

Last time we discussed the two types of research question, the first one is

descriptive and the second one is analytic, and then we said that we have

four different criteria for choosing a research question; first of all you have

to 1- choose a question that keeps you excitedwe dont want a research

that becomes boring at some stages because of the obstacles that may

appear every now and then, and then we said that 2- the outcome should

have an impact on the health ,we dont want a very bad research that does

not have any benefit to the society, and then you have to consider whatquestions you are ready to answer based on the 3-prevalence of

the disease in your area, your prior experience, your colleague, and your

community contacts, finally you have to make sure that the research 4-has

not been answered before, so no identical research has been done before,

you are not going to repeat what others had done unless you add

something new.

Now we continuo, we choose a study design afterchoosing a research question,

now we want to design the study in a very relaxing, easy, and useful way.

Slide 10: Choosing a study design

There is no best study design

The best study design is something impossible or very difficult, thats why we

try to choose a design that can be very good or excellent but we cannot choose a

perfect design, all researches should have difficulties at some stages that prevent

you from doing a perfect research design,

Determine the best study design to answer your question

The study design in all the time is set to allow you to answer the research

question

- Feasibility; is it feasible to do the research?

- Cost; is it expensive?

- length of time, risks and benefits on participants

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The best research is a feasible research with very low cost and it takes a

short period of time and has no risks but have many benefits on the

participants, this is the best ever research, but can we reach this research ?

Not necessarily, we try to be as close as possible to the best research design.

A bad research is not feasible very expensive, takes a long period of time,

has many risks and low benefits on participants or society.

Broad categories of study design, in general any study design has to belong

either to:

- Randomized studies

- Observational studies

Slide (11): Differences between randomized and observational studies

Randomized study:

Investigator manipulates the condition or group assignment

The researcher totally interfere in randomized research design, he is not just

someone who observe the facts and describes it, here we are making an

experiment, so the researcher has an important role in designing the research

and setting all the details of the research.

Observational study:

Investigator assesses a population without altering the condition or group

assignment of the population

We dont change the group assignments, we as investigators evaluate the

population, we observe the population, we record facts about the populationbut we dont alter the condition of the people.

Observational study: in my research timing of tooth eruption I just

examine teeth and I collect the data of their teeth, so I dont change the

condition in their mouth, I just open their mouth, examine their teeth and

record my data, this is observation

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Randomized study: I want to make a research to examine the effect of a

drug on the liver for example, I bring two groups of people, one is called the

treatment group and one is called the non treatment group, I give the drug

for the treatment, and for the other group I wont give this drug, I give an

alternative drug or a placebo* , and I see the effect on this drug on their

liver, this is randomized because I interfere by altering the condition of

the people, by giving them drugs and I didnt just observe without altering .

Its very important to understand the difference between them because we have

many divisions that need to be understood based on these.

In the randomized study, one group receives treatmentor medication or any

dental service, and another group receives a different treatment or placebo.

*Wikipedia: A placebo is a sham or simulated medical intervention that can produce a (perceivedor actual) improvement, called a placebo effect. /

Slide (12): Advantages & disadvantages of randomized studies

Better at dealing with confounding and bias, because you are controlling and

interfering in creating groups, and because these groups are randomized you

minimize confounding and bias.

Less generalizability, we cannot generalize the results or finding on another

group of people, so the generalizability is less.

Slower to conduct, in my research, timing of tooth eruption, which is

observational, in less than one hour I examined fifty students!! So its very

quick, and in less than forty visits, my colleagues examine three thousand school

children, so its very quick, but in the randomized study we have to do an

experiment; we have to bring a group and give them a medication and study the

effect of this medication on their bodies, so it takes long time.

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More expensive, in my research (timing of tooth eruption/observational study),

we examined more than three thousand school children for less than 700 JD, so it

is considered very inexpensive, but if you want to examine a drug (randomized

study) you have to bring lets say 100 participants and you test the drug on them,

of course they will not accept to have their body tested without being paid,

something like 50 or 100 JD, and there is the cost of preparing the drug, and the

cost of the testing or examination or blood sample, so randomized Is more

expensive.

Cannot answer as broad range of questions as observational studies

When I went to examine the school children for my research I said to myself;

I am not going everyday so in addition to examine the teeth I can also examine

the soft tissue and I examine the cusp of carabelli, so this research allowed

me to examine many other things at the same time, because of this I answered

a broad range of research question.

But if we do a randomized study like testing a drug, you are only answering one

specific question, what is the side effect of this drug, so its very specific, but

the observational is broader.

Slide (13,14): Confounding

We said that we have selecting, measurement and confounding bias,

confounding bias is really something serious, because its not easily avoidable,

selection and measurement bias can be avoided easily, but sometimes there is a

confounding bias that we are not aware of.

- In observational study: Association between a risk factor and anoutcome is affected by the relationship of a third variable (confounder) to

the risk factor or the outcome.

- Confounder in observational studies is :

Associated with the risk factor

Causally related to the outcome

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In randomized study, the effect

of confounder is only in one

way, it only affects the

outcome, but it does not affect

the categorization of group, or group assignment, but the confounder in the

observational study, it can affect the risk factorandthe outcome at the same

time, thats why we said that one of the advantages of the randomized study is

that it is better at dealing with confounding and bias, because its only affecting

on one direction, which is the outcome, but it doesnt affect the role of group

assignment.

We want to see the effect of diesel fuel on lung cancer; smoking can cause lung

cancer too, so its a confounder.

In observational study we examine all the people who inhale diesel fuel without

categorize them to smoker and non-smoker, so the confounder will affect the

risk factor (lung cancer) which will eventually affect the results.

In randomized study we categorize the groups to smokers and non-smokers, so

we isolate the effect of smoking in our results, which will lead to better

results

Slide (15): Eliminating confounding

How to eliminate confounding?

Randomizing subjects, this the first step

Randomization should be unbiased

The ideal situation to test a medication is to have very healthy people, but we

dont want healthy people to be in one group to receive the medication and the

other group we are not interested whether they are healthy or not, I want

both groups to be identical in the same setting, if we have 20% of ill people in

this group we should have 20% in the other group, but how can we make sure of

that? we cannot be sure, so we have to randomize, if we take random sample

for this group and random sample for the other group we eliminate or minimize

the role of chance, and it has to be unbiased too, so when I set the two groups,

I shouldnt know if the subject is healthy or not, otherwise it will be biased.

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Randomized groups will be e qual with respect to confounders, the effect of

confounder should be the same in both groups, like for example (smoking on

lung cancer), the number of smokers in this treatment group should be the same

as the number of smokers in the other group, if we have bias we should have the

same amount of bias in both groups.

Randomization eliminates known and unknown confounders, are all confounders

known?? Sometimes we are not sure of all the factors that affect the results, we

know that smoking is a confounder in the effect of diesel fuel on lung cancer, but

they may be other confounder that we are not aware of, like alcohol consumption

is another confounder, thats why we have known and unknown confounder, the

best way is when we eliminate all the known and unknown confounders, how?

By randomization we eliminate all the known and unknown confounders

Other techniques for minimizingknown confounders, which include:

- Matching:

If you know that smoking is a confounder in diesel fuel on lung cancer,

you can match, we only test people who are nonsmokers or only smokers,

and by this we are matching, (adjusting or selecting a variable).

If you want to see the effect of some medication on blood pressure for

example, and you examine people who are forty year old males in one

group, you have also to bring forty year old man in the other group, this

is matching, and by this you eliminate the factor of age, which is a

confounder in this case.

- stratification, multivariable adjustment

Slide (16, 17, and 18): Minimizing bias

Randomization eliminates confounding only when unbiased.

we dont want a researcher to come and make assignments or classification of

the groups based on things in his mind, we dont want a cheater or a researcher

who want for example healthy people in this treatment group, then he started

to invite people to his research and then he isolated the healthy people and put

them in the treatment group, and then the other group he was not caring

whether they are healthy or not, this is bias.

Group assignment should be done

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- At the time of enrollment, (when we ask the subjects to participate in our

research), not before or after, for example I ask the subjects to participate,

and then I ask them to provide their data, name, age etc, and then we do

the group assignment, after they enrolled I can see the data or the details

of the subjects, and based on that I can choose a design that helps me, orbrings good results, that is bias, which is wrong! For example I test a drug

on only healthy people.

Why not before?? Because I can already have in my mind that I will only

allow healthy people to be tested on this drug, and begin to choose only

healthy people, this is not correct, I want random people, because I want to

see the effect of this drug on healthy and ill people.

No group assignment change by personnel(people working on

the research).

- By someone with no contact with the subject, like brothers, because we

know the health rate of him.

- Using a random number table or generator, this is computerized test that

we use to give random numbers.

In observational studies, investigators and subjects usually know which group

the subject or examiner were assigned to, so it is not as accurate as in the

randomized study, in my observational study when I go to school to examine

children in tooth eruption I already know that the child I am examining is in the

fourth grade, so I expect to see certain teeth in his mouth, and I may change

some data in order to reach to the results I want, this is bias.

Investigators may have some expectation on what the outcome

would be (possibility of bias) for example I notice ,by chance

that a second molar is in the mouth of a fourth grade boy, I

surprised, and because this finding dont meet my expectations I

may think of changing it, this is wrong and not honest.

subject may leave this study if they know they belong to

controlled group, this is another disadvantage in observational

study, if for example the person knows that he is not in the

treatment group, and he will not receive the true medication, so

he will not be paid, then he may drop off the experiment, they

dont have to know to which group they belong to.

Minimizing bias is done by blinding; as an investigator I have to be blind, I dont

have to know any personal data or anything about them, and also the subjects

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they dont have to know to which group they belong, this is very difficult in

observational study, we have double blinded or single blinded studies.

Single blinded studies: for example if I as an investigator know that this

subject/patient belongs to the treatment group, and the other subject belongsto the placebo/non treatment group, but the subjects themselves dont know to

which group they belong. Or vice versa, I as an investigator do not know this

subject belongs to which group, he comes to me and I dont know if he belongs

to the treatment group, or non treatment group! But the subject knows to

which group he belong, but actually this is not useful, so single blinded is when

the investigator knows and the subject doesnt know.

Double blinded studies: it is when boththe investigator and the subject donot know to which group the subject belongs, this is double blinded; the best

randomized study is double blinded. I dont know and he doesnt know, but in

the observational study it is impossible, I know that this child is in the fourth

grade, and he knows that he belongs to the examinees, for example if I want to

examine people of having caries, he knows that this person has caries, we

selected him because of caries, so he knows that he belongs to the caries

group, not to the non caries group so we cannot control it in an observational

studies.

Double blinding is impossible with observational studies sometimes we can do

single blinded in observational studies in certain cases.

Slide (19): Generalizability

Generalizability refers to the ability to apply the outcomes of a study topopulations other than the study sample, this was discussed last time.

The results of a trial apply only to population s that resemble the study sample

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Slide (20) Generalizability and randomized studies

Generalizability is more a problem with randomized studies, why?

- Randomized subjects are different from the general population because

they carry more burdens, the person that you examine under strict

experimental rules is different from the normal person

When I bring a person and I put him in a treatment group and I give him

a medication and I say to him please take this medication every 2 or 3

hours, I give him strict rules and he then will be accurate, but a normal

patient is not as strict as that, so a normal person who takes any

medication even if the dr. said to you, take this medication three times a

day, do you take it every six hours exactly? not necessarily, you maytake it after lunch and after diner and so on, so I am not strict, but the

person in the experiment he has to be very strict, so thats why in

randomized study, the person under study is different than the normal

study, and we cannot generalize the finding in an accurate way to the

other populations.

- They have strict rules:Selection, blinding, previous exams and blood

testsetc

When we bring a lion and put him in a zoo, and examine the physical

characteristics of that lion, he will be different because he is now in a

different situation, naturally this lion has to be in the forest, he has to

be free, thats why the condition of this lion is different from the actual

lion who lives outside, so we cant generalize any experiment done on that

lion to the lions who live free.

- Trial conditions are different from those in clinical practice, the condition

of the experiment is different from the actual condition in the clinicalpractice.

Trial subjects receive more attention than the normal patient, I as a

researcher I give my subject more attention than I give my patients

who I normally treat.

Treatment works under tight research protocol

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We have two terms now: Treatment efficacy and treatment

effectiveness.

Efficacy: how well an intervention works in a research setting? When we

examine the effect of treatment in research setting, we call it efficacy of the drug.

Effectiveness: how well an intervention works in a clinical setting? If we are

working in clinical sitting not in research settings we call it effectiveness

Slide (21): Observational studies and treatment effectiveness

We want the observational studies not only for treatment efficacy we want also

treatment effectiveness; finally we want this medication to be applied in clinical

practice, not only in our research.

Closer together than in randomized studies, in observational studies, treatment

effectiveness and efficacy are very close, but they are apart in randomized study.

when I go to examine school children I examine them in the natural place where

they belong to, I dont ask him to come and put him in restrict research rules, so

thats more effectiveness, but if I put them in groups and do a research, then this

is efficacy. So the amount of difference between efficacy and effectiveness in

observational study is minimal, but it is huge in randomized study

Still some differences, even if the distance between them is small, there is still

some differences

- Observational study patients receive additional educational or testing

than normal clinical patients

I want to do an observational study, and I go to schools and I inform these

people that I am coming on Wednesday, so this child brushes his teeth because

he knows that a dentist will come and examine his teeth, so in this I affect theway he is living naturally if he does not brush his teeth daily.

- Observational study patients may change their behavior ( Hawthorne

effect); after a child knows that a dentist will examine him he may refuse.

Slide (22): Length of time to conduct

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Observational studies are faster to conduct than randomized studies, we already

discussed that

Especially with an existing database and the use of case-

control design, we will come to that

Slide (23): Minimizing expenses

How to make your research less expensive?

Observational studies are less expensive

- Especially with an existing database and the use of case-control design, if

we have already a data base present, we just add new information on the

data bases, this is much cheaper.

- Less markedly with prospectivecohort design, we will come to them later.

- Observers are just observing the outcomes, without experiments

Randomized control trials are expensive; we have to pay for the interventions

e.g. medicines, tests, appliances...Etc.

Slide (24): Addressing a broader range of questions

Can we ask a very broad range question in observational studies!? YES

- In many situations where it is unethical or impractical to randomize asubject, for example we cannot ask people to smoke or stop smoking! And

then examine the results! This is unethical, but we can bring smokers and

bring non smokers and doing tests on each of them, and see the

differences, in this way instead of doing an impractical randomized

research we do an observational study, we can examine smokers and non

smokers.

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- Randomized control studies are rarely helpful in identifying causes of

disease outbreaks, but the observational study can link the factor with the

disease, and give you some idea about the causes.

Slide (25): Indications of observational studies

When do we do observational studies?

Instances where it is unethical or impractical to perform a randomized study, so

randomized study is good but it has many disadvantages, when do we avoid

randomized study? When it is unethical! I dont bring people and ask him to

drink alcohol and examine their body! So instead of that I go to people who

already drink alcohol and I examine their body so observational instead ofrandomized.

Time is of the essence in obtaining the results, if time is important and I want to

do a research in a short period of time I do an observational study not

randomized.

THE END

As you can see this material depend on understanding more than memorizing, you may

become confused in some points but I try to write down every single word in a simple and

understandable way as much as I can

Bara2 told me that he will kill me if I dont write regards for him, SOOOO

Special regards to all our great dof3a>>>EXCEPT

(3) designing a study i

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