Lecture5 Research design II part 1 (script)

8/3/2019 Lecture5 Research design II part 1 (script)

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"In the beginning of the lecture the doctor said that he will changethe exam`s date, coz he will be in Australia on 27/11..and he willtell us the new date later"

Please refer to the slides while studying...

Last time we stopped at this stage here, we said advantages anddisadvantages of randomized studies, we discussed all of theseand we said one of them it's better at dealing with confoundingand bias because you can control (anything you can control) thismeans it's better to deal with these problems...But in observational studies you just observe, so thats why if youhave a problem you cannot sometimes control for that problem(ya3ne 2nta lamman tkoon bddak t3mal tajroba bnafsak tasta6ee3

an tata7akkam b jamee3 el 3awaml 2lle 3ndak laken lmman tkoonbddak ta36e 6'ahira mo3ayyana sometimes sa3b 2nnak tit7akkamb jamee3 el mo2athirat 2lle to2ather 3alee)SO in randomized studies (2lle tkoon 3la shkl) which isexperimental studies which you did it and you choose the persons(2lle bddak tf7ashom) that u want to examine and you divide themto groups thats why its much better to deal with confounding and

bias when you do randomized studies than when you doobservational studies

We said confounding is an association between risk factorand an outcome, when this association is effected by therelationship of a third period of time...

We always gives this example: you have for example effect ofsmoking on lung cancer,(lets say smoking on oral cancer) but also

we have the effect of alcohol consumption on oral cancer thats whyyou cannot study the effect of smoking on oral cancer alone without

considering those who consume alcohol because also alcoholconsumption can have an effect on oral cancer, also alcohol can

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effect smoking there is a relationship between alcohol and smoking(as you learned in pathology we have something called synergisticaction ya3ne for example if the effect of smoking alone on cancer

was 5 % and alcohol 5% you cannot say the effect of smoking and

alcohol 5+5 which is 10 % NO its 5 times 5 "ya3ne 25" so thats whythis is called synergistic action) SO if we want to see this considerthat we want to study the effect of alcohol on oral cancer you haveto consider the potential confounder which is smoking smokingcan effect on both ways in randomized studies you can control theeffect between smoking and alcohol consumption by assigns groups

by dividing the samples that we want to study into 2 groups 1 isthose who are smokers and the other group who consume alcoholthe other group who are normal (non-smoker & and not alcoholic)so you can control because you have the ability to assign groups (to

choose your groups) but in observational studies the possible effectis in both ways and cannot be controlled, thats why we go and say :Randomized studies are better at dealing withconfounding and bias.

Eliminating confounding by randomizing subject:as we said you can randomize(choose randomly) by this youeliminate the effect of confounding, when you choose a randomsample there is a possibility of choosing the people who have the

problem and choosing the people without the problem and becauseyou include a very big number of subjects, the effect of includingthose with a problem can be canceled with the effect of includingthose without the problem..Randomization should be unbiased, that means when you dorandomization ( mosh lazm ykoon fee ta7ayyoz) all the time dontlet your self know the groups that you are randomizing,if I want to do an experiment on my student in this theater I

should give each one of them a number I should not identify each

student by his/her name, otherwise I will not randomize,randomized groups will be equal with respect to confounders; theeffect of confounders should be equal among all those who aregoing to be selected.Randomization eliminates known and unknownconfounders:Sometimes the confounder it can be known like for example: when

you know confounder of alcohol consumption on oral cancers, bythis we say the confounder is known!! But sometimes you dontknow the other confounders, sometimes you discover them by the

end of the research and sometimes you dont discover them...that'swhy we have KNOW and UNKNOWN confounders

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Randomization helps in eliminating know and unknownconfounders:Other techniques for minimizing known confounders when you

identify a confounder and you want to eliminate it, you can domatching, stratification, multivariable adjustment, for examplewhen you take Jordanian population and then you divide it intonorthern, middle and southern regions you take each region youselect the biggest state in the northern region for example which isIRBID and then you take govern Irbid divide into rural and urbanand then in each rural you take one randomized school for boysanother randomized school for girls, by this we cause stratificationso you start with the head of the urban area and then you start tostratify (tballesh t8assimhom) this is very good in eliminating

confounders..(I don't want to go in details of matching andmultivariable this will be discussed next time Insha'Allah, justknow that these are techniques that I use to eliminate theconfounders)

Randomization eliminate confounding onlywhen unbiasedas we said, group assignment should be done at the time ofinvolvement not the before or after, if you want to do randomize astudy and you want to select the groups or you divide your samples

into the groups that you want to study, this should be done at thetime of involvement (ya3ne lmma yejo yishtarko 3ndak bl ba7eth fhathak el wa8t 2nta btballesh, mosh walla yballesho yishtarko w

ba3deen 3la mazajak wjadt results mosh naf3a ro7t 8assamthom2la groups mo5talifa marra thanya!!!) NO that (randomization andgrouping) should be done at time of involvement of your subjectsinto your study, not before and not afterNOTE: (no group assignment should be changed bypersonnel, and should be done by someone with no

contact with the subject)!!!!!!!!!! that means if I want tomake a study, there should not be a contact betweeninvestigator and the subject " like for example if I want tomake a study about YOU, I have to bring someone else tomake this study because I know YOU all" so it should bedone by someone with no previous contact with thesubject

By using a random number table or generator (ya3ne bn36y kolwa7ed a random number, w lazm kol wa7ed ykoon 3ndo chance

2nno ykoon b had el group aw hdak el group, mosh 2nno a7o6homzay ma ana bddy 3ashan a6alle3 el result 2lle ana bddiyyaha!!! NO

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lazm tkoon RANDOOOMMM, unless if your study will involvepeople with those who will take the treatment and those who willnot take the treatment, in this case you have to know for example if

you want to study something you want to group the people (people

with disease and people without disease) you have to give thosepeople the same antibiotic as the other group without the disease inthis case you have to know you have to group those with the diseasein one group and those without the disease in the other group, butin the cases if there is a randomization, each one or each grouphave the same chances to belong to each one of the groups

In observational studies, the investigator and subjects usuallyknow which groups the subject where assigned to (in the case ofobser. studies we know for example when I did my study on

emergence of permanent teeth, I previously know that today I'mgoing to a rural school so thats why I know previously that thesubject that I will examine today for example they have an increaseperiod of caries because they live in a rural area not very serviceareas, (man6a8a 3'eer ma5dooma)..In observational studies its very difficult to control the groups

because you know that you are checking a case, so sometimes youexpect what to see, but in randomized study you can control thatand it can be better to control

(The doctor repeated the same example in Arabic but in anothercase)

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NOTE: in observational studies you can expect theoutcomes, but in randomized study you dont

One of the disadvantages of randomized studies, subjects

sometimes they can leave the study if they know (for example if Idivided my students into two groups I will give one of them a drugand the other group I will not give them the drug, ANAS :D knowsthat he is in the group that will take the drug ,so he say (ana

bddeeeeeesh:D ) are you trying the drug on me!! Then he leaves thestudy!!! Thats why it's very imp. that in the randomization studies

you should not be in contact with the subject (the students that aregoing to be in the study) and they should not know to which groupthey belong to SO IT HAVE TO BE RANDOM, and no one knowhis/her group the observer should be blind about the subjects

and the subjects should be blind about the observer (ma lazm elobserver yo3rof el subject w ma lazm el subject yo3rof el observerhad esmo BLINDNESS)the best study design is called DOUBLEBLINDED STUDY what does it mean?????????????The observer is blind about the subject and vice versa...

IMP. NOTE: in randomized study, it has to be doubleblindedbut it's difficult in observational study to bedouble blinded

Blinding in randomized trial helps in preventing both theinvestigator and the subjects from knowing groups assignment,(thats why I know that Anas is a clever student (temzaaa7) so Ishouldnt know that he is a clever student otherwise I may thinkabout putting him in a group that favors the result (a5ally fe group2nno ykoon el result better) but I dont have to know him, and also

Anas should not know his group because maybe he will not like thatso this is not good)..

When the investigator knows the subject and the subject dontknow the investigator so we call this SINGLE BLINDNESS, and

vice versa

PLEASE be careful about these, coz I will bring examplesin the exam and I will ask you if this is single or doubleblindness..!!

For example I will bring you in the exam when the

investigator knows nothing about the subject and the

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subject know nothing about the investigator, this type ofrandomized studying is .????You should know that this is "DOUBLE BLINDNESS"

But if I bring you a Q, the investigator knows about thesubject but the subject know nothing about theinvestigator so this should be "SINGLE BLINDNESS"

If the subject and the investigator know everything abouteach other then this is called "UN-BLINDED STUDY"

Double blinded is impossible with observational studies,it's very impossible! to do double blinded in observational study,for example if you are going to do a study about the cusp of

Carrabelle in a certain school "in a certain town" so you alreadyknow where will you do the study (subjects) but they dont know

you so in this case its SINGLE BLINDED..

So in observational studies it's impossible to do doubleblinded study but it's possible to do single blinded

Generalizability: refers to the ability to apply the outcome of thestudy to populations other than the sample...

As we discussed in the first lecture we said that the result should begeneral I can do it on another sample if I took it from the samepopulation or I can do it on the same population!!!!!!!

The result of a trial apply only to the population thatresembles the study samples, in the case of trial or in the caseof randomized study (we call it clinical study) el nateeja to6abba83la el nas 2lle 2nta 2shta3'alt 3aleehom, mn el sa3b 2nne

a6abbe8ha 3la nas thaneen, but in observational study maybe thegeneralizability can be much better..

Generalizability and randomized studies:Randomized subjects are different from the general population

because they carry more burdens (a3ba2)...when I want to try adrug that I made it by myself, when I want to try this medication I

bring people with the disease and people without the disease and Itry the drug here and here, halla2 el mosharek bl ba7eth ma ra7

ykoon mrta7 lesh?? l2anno ta7t el tajroba, f bl taly ra7 ykoon 3alee

a3ba2 7as 2nno fe 3b2 w ga3d ya5od el drug w howwa 5ayef "6ab

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balky had el dawa 3mlly 2she mathalan!!" w ymkin 7alto el nafsiyyat2ather 3ala el nata2ej el motawa88a3a 3la el ba7eth....

Ya3neeeeeeeee THE PSYCHOLOGY OF THE SUBJECT

(PATIENT) MAY EFFECT ON THE RESULT...

Trial conditions are different from those in clinicalpractice: trial subject receive more attention el nas 2lle bl ba7ethmodallaleen, lmma ana ajee a7o6 anas bl ba7eeth bkoon mdalliloo,ma36ee 6'roof momtaza mosh m5allee 3la 6abee3to f bl taly ma

btkoon el nata2ej zay ma bdna)...

Treatment works under tight research protocol, when I want to trythis drug there will be approach very tight and instructions and I

will say: ANAS you will wake up early in morning and you have toeat breakfast then you take the drug etc. so he is under abnormalconditions, if I leave him without study maybe he will not eat

breakfast every morning so the best way is to make the study undernormal conditions of the human

I will differentiate to you between treatment efficacy and treatmenteffectiveness!!! efficacy have well work on research setting, if u

want to study something, if u want to see how the things will work

in the setting of the research this is called efficacy..For example: I brought Anas to my study and I tried a drug on

him, and I gave him the instructions tight bla bla (katha w katha)then I say this is the efficacy of the drug not the effectiveness

because I put Anas on the conditions of the researchBut for example I put Anas on a normal conditions but he doesn'tknow, and he started to take the drug and he take it once and leaveit once, he take it on 7 a.m. and sometimes he take it on 8 a.m.Because he doesn't know, so in this case I will say the

EFECTIVENESS of the medication

NOTE: efficacyis different from the effectiveness..!!EFFICACY: related to research settingEFFECTIVENESS: related to clinical setting (el 6'roof el6abi3iyya el saririyyaa)

PLEASEEEEE UNDERSTAND THE DIFFERENCE WELLBECAUSE THERE IS A QUESTION ABOUT THEM IN THE

EXAM

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Observational studies and treatment effectiveness closertogether than in randomized studies, in the case of observationalstudies the efficacy and effectiveness are exactly the same or veryclose to one another, (fe 7al el observational lmma bddy aroo7 af7as

a6fal fe almadares, bykono fee 6'roofhom el 6abi3iyya!! F 2llebykoon mf6ir w 2lle mosh mif6r, f hay hyye 6'roofhom el6abi3iyyaa, so efficacy btkoon nafsha el effectiveness but inrandomized studies NO, the efficacy is different)But we still can detect some differences in observational studies

between the efficacy and effectiveness..!!observational study, the patients receive additional educational ortesting than normal clinical patient ((momkin mathalan hadool ela6fal 2lle ana af7ashom bl madares, 3rfat el modeera 2nno 27na

jayyen bokra 3l madares w ra7at yalla bokra jayyekom a6ibba2

asnan 3l madrasa w bdhom yf7asokom f kolkom btejo 3l madrasaw mfarsheen asnankom, 6ab ana jay af7as el plaque indexmathalan mo3addal kam 3ndhom plaque, ra7at el modeeram5arbatly kol el sho3'ol taba3y!! f bl taly ymkin t5talef el efficacy3n el effectiveness l2any ma fa7asthom b 6'rofhom el 6abi3iyyal2anno el modeera tda55alat.))

Thats why we have a different between the efficacy and theeffectiveness

observational study patients may change their behavior,and this is called Hawthrone effect as I said sometimes if theyknow, if school children know previously that those investigatorsare coming and examining them tomorrow they may change their

behavior (momkin bdna n8ees m8dar mosha3'abat el 6alb, f ra7aboo w ommo 7akolo 2nno yseer mohaddab bes howwa bl 3ade6alb sha8y) so thats why they may change they behavior

- Length of time to conduct:-

- Length of time to conduct observational studies are faster to

conduct randomized studies

in observational studies you can examine subjects once (betro7

2nta 3la almadrasa btef7a9 hal madares bejoz al6aleb yenfa7a9

mara wa7de fa momken 2nta fe 2sbo3 zaman tef7a9 3ashar

madares 2t5ale9 al study) thats why it is very fast to conduct. but

in randomized study (bedak 2tjeeb nas 2t7o6hom ta7t al tajrobanas ta36ehom al dawa nas ma ta36ehomsh bedak todroshom 3la

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fatra 6awele 3ashan 2tshof al effect of that medication) you will

bring a group of subjects and put them under experiments and

tests that take a long time to conduct that is why we are faster in

observational than randomized, especially when existing database

and the use of case-control design _we will discuss what we meanby control design (fe 2l m7adra al 8adema ) in the next lecture_

(lama ykon 3na 8a3dat bayanat kbera zay mathalan madares al

Jordan fa bettaly hek 7ale ne3mel al study be shakel saree3).

- Minimizing expenses:-

Observational studies are less expensive than randomizedstudies:-

(lesh efre9o ene bede 23mal ba7eth 3la 2tfal madares al Jordan ma

bedha ma9are ktheer fa8a6 al ba7eth ra7 ykoon 3la taklofat al

na8el lal ba7theen mathalan w 2tha fa8a6 2dawat al fa7e9 al

base6a 2lly momken yf7a9o feha 2snan al mar9a) for example

when I do research on school children in Jordan I just need money

for transport and simple examination equipments thats why it

isn't inexpensive but randomized studies are expensive (ba39 al27yan 3shan 28ne3 b39 al nas yshtarek fe alba7eth w 236e dawa

lazem 2dfa3lo mabla3 9a5em la2no momken fe 2y la76a ye7ke ma

bedy) for example if I want to do a research on a drug I have to pay

lots of money to subjects to convince them to take a testing drug!

-Observational study is less expensive specially when existing data

base. sorry (hay 2lno86a sa8a6at sahwan men alslide al 8ablo)

dont worry about it. "Remove it from slide 23"

-Less markedly with prospective cohort design:-

(fe 3nde designes mo3ayane 9a3eb 2ne 2shra7elko sho ya3ne )

prpspective cohort design (laken momken nerga3elhom la7e8an

lma ne7ke 3anhom ra7 tefam hay al no86a ta7dedan sho 3la8et al

expensive be hade al design ) it is hard to explain what we mean by

this now we will come to it later on and you will understand it.

Slide 23:

Observes are just observing the outcomes :-

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Thats why it is less expensive you just observe the outcome you

dont control actually you can't pay your subjects for example.

Randomized control trials are expensive :-

Because you need sometimes to pay for all of the interventions (kolal 2jra2at al bedak te3malha bedak tedfa3ha, bedak tedfa3 thaman

ta9nee3 al dawa al ra7 tjarbo, bedak tedfa3 la subjects bedo fatra

6aweely. bedak mathalan tsha3el nas ma3ak be al ba7th la fatra

6awely bedak tedfa3elhom rawateb fa be al taaly bedo yekon

expensive mathalan bedak tes7ab menhom 3aynat dam, bedak

te3malhom Lab tests la hay al 3aynat) so in randomized studies

you have to make lots of procedures and pay for them tests and lab

samples and stuff like that! Thats why it will be very expensive.

Addressing a broader range of questions:-

Observational study are able to answer a broader range of

questions:-

(el observational studies be tefta7lak 2faa8 ktere, adrobelkom

mathal : Ana 23melt study 3la timing of emergence of tootheruption laken be ma 2ne raye7 w 6ale3 2f7a9 kol al 26faal be

al Jordan lesh ma 2f7a9 al 2shya2 al tanye other dental findings

fa men al 2shya2 altanyee al fa7a9tha bel mar9a al cusp of

Carrabelle we 23melt ba7th 3n al cusp of Carrabelle ya3ne be

2mkanak teshmal 2shya2 kteer we teft7lak 2fa8 laken ) the

observational studies opens up your horizon, for example when

the Dr. did his research of tooth emergence he thought to

himself why don't I study other things such as cusp of Carrabellewith usual clinical trials you just answer the specific question

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you want to investigate (2nta bedak 2tjarb dawa 3la mar9a we

al nateja taba3tak hal al dawa kowayes wela mosh kowayes hal

dawa be3alej Al marad wela ma be3alej Hal dawa elo side effect

wela la )

You just answer one single question related to this specific

problem of your research but in observational studies you cananswer a very good number of questions.

Many situations where is unethical or impractical randomize

subjects you cant randomize person to smoke or not to smoke

but (ba39 al 27yan fe randomization ma be 2mkanak teje 3la

nas yala 2nto mosh moda5enen da5no we btdroshom, ba39 al

27yan unethical 2no te3mal 2l randomized studies ya3ne 3eer

25la8ee right? Lethalek beycoon al nata2j daye8a jedan).

Randomized control studies are rarely helpful in

identifying causes of disease outbreaks

(ya3ne ba39 al 27yan fe randomized studies ma be 2mkanak

2nak tet3araf 3la 2sbab al mara9 la2no 2nta fa8at todros she2

wa7ad ok 3aleban 2nk btodros association between something

and another thing) sometimes in randomized studies you can't

identify the causes of a disease and it is difficult to develop the

outcome relationship.

Indications of observational studies:-

When we do observational studies?

We do it in instances where it is unethical or impractical to

perform a randomized study

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(lama ykon mosh monasb 25la8eyan 2w mosh 3amaly

randomized study ba3mal observational study ya3ny mosh

ma38ol 2ny 2jeeb nas 23dad kpera kteer we nas 236ehom al

dawa we nas la2 fa bettaly be9eer moklef 7.edan al ba7eth lethal

bajebo 3la group 2z3eer lethaalek fe ba39 al 27yan ba3malrandomized study la2 bashmalo o ba3mal observational study

2shal ok ).

When time is the essence of obtaining the results (ba39 al27yan 2na bdee nata27. fe fatra 8a9era fa lesh 2ne 23mal

randomized study ya5oth menne santen 2w thalath ba3mal

observational be shahar o ba5ale9 fa ba39 al 27yan al time

elo dor mohem)

And now We start in a new topic:

Research design II

Types of randomized control trials:-

Now we so far know that we have two broad types of studies:

1) Observational study.

2) Randomize study.

We knew what are the advantages and the disadvantages of each.

Now we come to different type of each of two studies (hala kol

wa7da menhen 2tkon 2lha 28sam mota3adeda ya3ne) randomized

control trails may be in simple randomize design, cross over design

or factorial studies.

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In simple randomize design :-

-We randomize to two or more groups ( benjeb al nas

bn3malhom randomization ben8asemhom 3shwa2e ela majmo3ten

aw thalath majmo3at we 3la hada 2smo simple randomize design)

so you bring your subjects and randomize them and then divide

them into groups

it is simple and very powerful and this is done when enough

subjects are available and can be recruited (lma ykon fe 3nde 3dad

jayed men al nas momken 2ne 2sta8demhom lal ba7eth mathalan

bede 23mal study 3lekom masha2allah (250) 6aleb fa bettale be kol

sohole momken 28asemkom ela majmo3teen : majmo3a 236eha

2s2la sahla , we majmo3a 2s2ele sa3ba 7ta 23mal hek lazem

28asmkom 3ashwa2yan mosh hek 2tha bede 23mal hal al study

mosh ma38ol mathalan hay al jeha sha6ra 5otho al 2s2la al sa3ba

ra7 23ref 2no ra7 2tjawboha we mathalan hay al jeha 293af

ta79eleyan fa 236ekom al 2s2ela al sahla la2 lazem 2tha bede

2droskom 28asemkom ela majmo3teen we 236ekom nafs darajat also3obe ma 2kom 3aref ana men 8asamet ya3ne lazem 23rof ana

eno kol al 6olab sawasya fe ta79elhom mathalan al thaka2e 7ta

2tkon al nata2j ma38ola o man68eye) for example if I want to do

a study on you for example we have a large number 250

masha'ALLAH and I should randomize you and should not know

who is a good student and who is not and so on thats what we

call it simple randomized design . We do it when we have enough

number of subjects.

In cross over design :-

Subjects are randomized to one study group after a specific periodof time; the same subjects are switched to the other groupso incrossover design there is one group not twoFor example: when we give a group of students set of questionsthen after a month we give the same group another set of questions.So when we study the same group twice this is called crossoverdesign.

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Advantages:

Gives two subjects for the price of one

Instead of taking two groups we take one & we pay for one grouprather than two.

Less variability and more powerBecause we study the same group twice there is no variation,, forexample if I decide to study the intelligence in your class & I

randomize you into two groups there may be group more intelligentthan the other,,, so when we study one group twice there is less

variability and less variation means more powerful.

Each subject serves as his/her own controlIncrease subject motivation

You increase the participation in your studyAnd all subjects will be in treatment group at some stage,, forexample if we suppose u have two groups for study and you give

one of them a drug and dont give the other the participants in thefirst group may be worried and may not participate in your study,,

but when they know they are all wont take the drug in the firstexperiment and they will in the second here you increase themotivation of them to participate in the study.5. Good when you cannot recruit enough subjects

When do we do crossover design??When its difficult to take two groups so we take one and study ittwice.

Disadvantages:

Bias due to carryover effects leading to failure to ascribesuccesses or failure to correct group.For example: to treat a specific infection,, lets suppose you give agroup antibiotic A for 3 months then you give them antibiotic B forthe next 3 months,, and the infection reappear in the 4th month,,then you dont know if the reappearance is due to failure ofantibiotic B or if the infection is actually is present during the 1st

three months but not manifested.

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To overcome carryover effect >>>>>>washout periodMeans always let an enough period of time between the 1st

experiment and the 2nd one to ensure that the effect of the

experiment 1 finished before the beginning of experiment 2.

Factorial studies:The third type of randomized control trials, its designed to answermore than one question by randomizing each subject to more thanone condition.

For example: you make randomization to study the effect of

plaque on gingivitis and make another randomization to study theeffect of plaque on caries,, in this case you answer more than onequestion:The 1st >>>what is the effect of plaque on gingival health?The 2nd>>>what is the effect of plaque on caries?

And this is called Factorial studies

Advantages:1. Get two studies in price of one.

2. Cost effectiveDisadvantages:Different conditions may affect one another (interact)For example: what is the effect of lack of oral hygiene on cariesand what is the effect of lack of oral hygiene on periodontaldisease,, and may the 1st case affect on the 2nd case.

Before I finish sorry sometimes I speak in Arabic in this course andI hope this is not a big problem for Malaysian students,, plz anyoneof the Malaysian if you dont understand the example plz raise yourhand and I am ready to repeat the example in English.

Done By: Musap AL-rawi and Omar AL-jaaf

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((I tried to translate all the examples but I couldnt:Ssorry,I hope that It will not be a big problem))

This is my first script,so forgive me if there is mistakes,Itried my bestSpecial thanks for mohammad rafay3ah and karam

mukhallalatiHazem frieh: 7abeeby sa33oooby treed mosa3ada?? :P

If the world were a single state,

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Lecture5 Research design II part 1 (script)