types, architecture and hierarchy of research studies

8/13/2019 Types, Architecture and Hierarchy of Research Studies

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Types, Architecture and Hierarchy ofResearch Studies

Abdel-Hamid Serwah, MDProfessor of Internal Medicine

astroenterolo!y"linical #pidemiolo!y $nit, %&M, S"$, #!ypt

'()* - )+*+


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Objectives of the talk

To identify the types and architecture of different study

designs.

To identify the hierarchy of study designs

To Address the applications of each type

To identify the pluses and minuses of each type


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Are All Types of research studies

alie

May any one study type replace

the others


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Some Research Questions?

oes obesity have bad effects on health?

!s "eight reduction beneficial?

!s #$% better than the called traditional learning?

!f you met "ith a strange or ne" phenomenon& ho" do you deal "ith?

'ongenital anomalies and drugs given during pregnancy?

!s the ne" discovered drug better than the available one?

Are smokers at higher risk for (rare cancers) than non smokers?

!s *# carcinogenic?


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Types and *ierarchy of Study esigns

escriptive

'ase report 'ase series Survey

Observational

Analytic

Observational 'orrelational

'ross sectional 'ase+control 'ohort studies

,-perimental Randomied

controlled trials

Strength of evidence for causality between a risk factor and outcome

Other Studies: Systematic review

Meta analysis

Cross over

N of 1 trial


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'ase Series

/hat are they?

Author describes some interesting or intriguing observations

that occurred to a small number of patients

'haracteristics0

escriptive

The simplest design

%ead to hypotheses subse1uently investigated by other types

2'ase+'ontrol& 'ross+Sectional or 'ohort study3

4enerally over short period of time

4enerally no controls


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"ase Series . "ase Reports


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Observational / Analytic Studies

'ross Sectional

'ase+'ontrol

'ohort

,-perimental

5o+o-perimental

Attempt to establish a causal link bet"een a

predictor6risk factor and an outcome.


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Cross-sectional Study'

escriptive value0

*o" many 7niversity students smoke?

/hat is the age and se- distribution and school year of7ni. students "ho smoke?

Analytic value0

!s there an association bet"een regular smoking and test

scores among 7ni. students?

7nivariate

8ultivariate 2controlling for (confounders)3


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'ross+sectional Study0 Advantages

Yields Prevalence (not incidence)

Relatively Fast and Inexpensive - no waitin!

"o loss to #ollow up

Associations can be studied

$ay study several outco%es

&ontrol over %easure%ents

&an be used to assess prora%s (Pre/Post study)


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'ross+sectional study0 isadvantages

Provides only a snaps'ot in ti%e

&annot deter%ine causality

oes not yield incidence

Potential bias in %easurin exposure

&annot study rare outco%es


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Cross-sectional study'Disadvantages

time

- Cannot determine causality

Heart diseases

Smoking


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Measures of association

Disease (Outcome)

Yes No

Risk

Factor(Exposure)

Yes A

No C D

Risk ratio(relative risk)

AA !

CC !D

Risk ratio(relative risk)


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(hat if )are Cases$

Congenital anomalies in relation todrugs given during ppregnancy .

)is* factors of rare cancers#

diseases

Case Control Study


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Structure of "ase "ontrol Studies

DataAnalysis

Outcome!"osure


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Case Selection

+ Case definition

, e.g. lung cancer confirmed by biopsy

ncident cases'

+ )ecruit ne& cases at time of disease occurrence

+ etter for ma*ing inference about associationbet&een ris* factor and developing the disease

Prevalent vs. incident cases

, Prevalent'

+ )is* factors may be more related to survival &ithdisease than development /incidence0 of disease

+ f many people die soon after diagnosis1 may over-represent long term survivors

,


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Selecting Cases /cont.0

!ncident cases are preferable to prevalent cases for

reducing0

recall bias and

over+representation of cases of long duration

The most desirable "ay to obtain cases is to include all

incident cases in a defined population over a specified

period of time


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Selection of 'ontrols0 Sources

The controls should be dra"n from thepopulationof "hich

the cases "ere recruited.

Sampling 9rames for selection of controls0

+ #opulation of an administrative area

- *ospital patients

- Relatives of cases 2spouses : siblings3

- Associates of the cases 2neighbors& co+"orkers& etc3


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Sources of cases and controls in 'ase 'ontrol Studies

Controls Cases

;Sa%ple o# eneral population

;"on-cases in a sa%ple o# t'e

population

;All cases dianosed in t'e

co%%unity

;All cases dianosed in a sa%ple

o# t'e population

;Sa%ple o# patients in all

'ospitals w'o do not 'ave

t'e disease

;Sa%ple o# patients in t'e sa%e

'ospital w'o do not 'ave t'e

disease

;All cases dianosed in all

'ospitals (or in sinle *)

;Spouses+ siblins or associates

o# cases

;Any o# t'e above %et'ods


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#atients0 Sources of !nformation on ,-posure

Sources of information on e2posure'

Patients

parents' in children or severe illness.

)elatives1

Hospital records1 3mployment records1 etc.

(hen information is obtained via

intervie&s1 recall bias is often a concern.


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Measure of Association in "ase"ontrol Studies

DataAnalysis


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8easures of association in case control

Studies

Disease Status

Case Control

Exposure

Yes A

No C D

Odds ratio

A ,

. , &


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Odds Ratio 2OR3

A ratio t'at %easures t'e c'ance or lieli'ood o#

exposure#or cases co%pared to controls

Odds o# exposure0 nu%ber exposed nu%ber

unexposed

OR "u%erator1 Odds o# exposure #or cases OR eno%inator1 Odds o# exposure #or controls


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2334335otal

44266"on-s%oer

789774S%oer:xposure

Status

"o &*

(&ontrols)

&* cases

(&ases)

isease Status

,-amples0 'alculating the Odds Ratio

Odds Ratio 0 0A

.&

774 x 442

789 x 66

0 794


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!nterpreting the Odds Ratio

5'e odds o# exposure #or cases are 794 ti%es t'e

odds o# exposure #or controls

5'ose wit' &* are 794 ti%es%ore liely to be

s%oers t'an t'ose wit'out &*


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433433

5otal

77323"o Alco'ol

;3793Alco'ol:xposure

Status

"o &ancer&ancer

isease Status

Alcohol 'onsumption and %aryngeal 'ancer

Odds Ratio 0 0A

.&

793 x 773

;3 x 23

0 26;

The odds of alcohol consumption are times greater among

those "ith laryngeal cancer than among those "ithout cancer.


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OR"# OR$# OR%#

Odds o#exposure#or cases arereatert'an

t'e odds o#exposure #orcontrols

Odds o#exposure aree


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ORs& #+alues and >@ '!s for 'ase+'ontrol Study"ith B ifferent Sample Sies

Sample Si&e

Para%eter&o%puted n043 n0>3 n0>33

OR C.D C.D C.D

p-value D.@DD D.CDD D.DDE

;>? &Is D.@+F.F D.>+


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Strent's o# t'e &ase-&ontrol Study

8ost efficient design for rare diseases

!t shortens the "aiting time re1uired by cohort studies

'an be used "hen R'T is not logistically or ethicallyfeasible.

,fficient& 1uick and easy& cost effective& fe"er practicalrestrictions

Re1uires a smaller study population than a cohort study

'an establishes an association 2Odds Ratio3

7seful for generating hypotheses 2multiple risk factors canbe e-plored3.


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'an not prove causality because of0

7ncertainty of e-posure+disease time relationship

The e-istence of confounding factors

5ot efficient for studying rare e-posures

Subject to biases 2recall : selection bias&

misclassification3

isadvantages of 'ase+'ontrol Studies


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Correlation and

)egression


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Correlation and )egression


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"orrelation

What type of relationship eists !et"een the t"o

#aria!les and is the $orrelation si%nifi$ant&

x y

'i%arettes s(o)ed per day

*$ore on *+,

-ei%ht

-o.rs of ,rainin%

/planatory

01ndependent2 3aria!le

Response

04ependent2 3aria!le

+ 5.antitati#e relationship !et"een t"o inter#al or ratio

le#el #aria!les

6.(!er of +$$idents

*hoe *i7e -ei%ht

8.n% 'apa$ity

9rade :oint +#era%e

1;


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"orrelation

Measures and describes the stren!th anddirection of the relationship

/i0ariate techni1ues re1uires two 0ariablescores from the same indi0iduals 2dependent

and independent 0ariables3 Multi0ariate when more than two

independent 0ariables 2e4! effect ofad0ertisin! and prices on sales3

5ariables must be ratio or inter0al scale


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Negative Correlationasxincreases, y

decreases

x= hours of training (horizontal axis)

y= number of accidents (vertical axis)

Scatter Plots and !ypes of Correlation

=

?=@=

A=

B=

=

= A ? < C B= BA B? B< BC A=

-o.rs of ,rainin%

+$$idents


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Positive Correlationasxincreases,y increases

x= !" scorey= #P!

#P!


$%&&'%'%&

'%&&*%*%&*%**%&&

+%&

+%

'%*

'&& '& $&& $& && & && & && & &&

.ath !"


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No linear correlation

x= height y= /0


+&

+&

+$&

+'&+*&

++&

+&&

1&

&& $ * &

-ei%ht

1;

Scatte #lots and $ "es of


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Strong' negatie relationsip

*ut non-linear+

Scatter #lots and $y"es ofCorrelation

Correlation Coefficient r


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Correlation Coefficient r

! measure of the strength and direction of a linear

relationshi2 bet3een t3o variables

"he range of ris from + to +%

/f ris close to +

there is a strong2ositive

correlation%

/f ris close to + there

is a strong negativecorrelation%

/f ris close to &

there is no linear

correlation%

+ & +


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&utliers44444

Outliers are dangerous

Here ,e ae a spuriouscorrelation o r$./01

,itout 23' r$./41

,itout 23 5 6E'r$./7#


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The correlation coefficient of number of times absentand final !rade is r6 7(489:4 The coefficient ofdetermination is r' 6 27(489:3' 6 (48:(;4

Interpretation< About 8:= of the 0ariation in final !radescan be e>plained by the number of times a student isabsent4 The other := is une>plained and can be due tosamplin! error or other 0ariables such as intelli!ence,amount of time studied, etc4

Strengt o te Association

The coefficient of determination, r', measures

the stren!th of the association and is the ratioof e>plained 0ariation in yto the total 0ariationin y4


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Cohort study

"on-32perimental32perimental


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Prospective1 longitudinal1 follo& upStudies' Cohort

A cohort study is a0

'omparative

Observational6 analytic studySubjects are grouped by their e-posure status

All subjects& are follo"ed for"ard in time to determine

if one or more ne" outcomes 2diseases3 occur

The rates of disease incidenceamong the e-posedand

une-posed groups are determined and compared.


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Architecture of 'ohort studies


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,lements of a cohort study

Selection of sample from population

8easures predictor variables in sample

9ollo" population for period of time

8easure outcome variable

Famous cohort studies

9ramingham

5ursesH *ealth Study 25*S3

/omen health !nitiative 2/*!3

#hysiciansH *ealth Study


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"ohort studies< Marchin! towards outcomes

Lancet*&&*4@>DE'$+-$

"he defining characteristic of all cohort studies is that the5 trac6 2eo2le for3ard in

time fro( epos.re to o.t$o(e% 7ata collection ma5 be 2ros2ective orretros2ective% /F 'ontra$epti#es and 43,%


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"ohort studies< marchin! towards outcomes

/posed s.!Ge$ts

Hneposed s.!Ge$ts

'lassi$ 0'on$.rrent2

'ohort *t.dy4isease

4isease

,oday I >J >J B= I B=

-istori$al

06onJ$on$.rrent2

'ohort *t.dy

/posed s.!Ge$ts

Hneposed s.!Ge$ts

4isease

4isease

"ime in 8ears

,oday I >J >J B= I B=

"ime in 8ears


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Cohort Study' Design 4utlines


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:xperi%ental Studies1 &ontrolled trials

,-perimental drug or procedure compared

"ith another& "ith a placebo& or "ith thestandard procedure.


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Structure o# R&5 Studies


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,-amples of 'ohortStudies


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Schematic 4utline of StudyDesign


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)C!' )esearch 5uestion

%s Mass treatment of sc&isto' more effective t&an

treatment of "ositive cases after stool analysis


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Mass !reatment 6s. Stool analysis and treatmentof 7ve Cases

Study #o"ulation


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5urseHs *ealth Study 25*S3

5one-perimental esign

Individuals classified according to "hether they

received *ormonal Replacement Therapy 2*RT3& or

notSubjects "ere follo"ed for various health outcomes0

heart attacks

strokes

breast cancer and so on.

Exampleof publication0 Stampfer& 8.& 'oldit& 4.& /illett& /.& 8anson& I.& Rosner& $.& Speier& 9.& et al. 2E>>E3.#ostmenopausal estrogen therapy and cardiovascular disease. Ten+year follo"+up from the nursesJ health study.NewEngland Journal of Medicine, 3252EE3& F@G+FGC.


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5urseHs *ealth Study 25*S3 5on+

e-perimental esign

8Healt outcomes8 eart attacks' strokes' *reast cancer and so on/

/omenHs *ealth !nitiative 2/*!30 ,-perimental esign


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/omenHs *ealth !nitiative 2/*!30 ,-perimental esign

!he (H study randomly assigned about half its sub9ectsto'

- Group :' that received hormone replacementtherapy/H)!0.

- Group ;. received an identical loo*ing placebo.

%ll Sub9ects &ere follo&ed for


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/omenHs *ealth !nitiative 2/*!3

,-perimental esign 2R'T3

Healt outcomes8 eart attacks' strokes' *reast cancer and so on/


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'omparison of /*! and 5*S

$oth analyed relationships bet"een *RT 2e-planatory

variable3 and various health outcomes 2response

variables3

/*!investigators assigned the e-posure 2*RT3

e-perimental

5*Sinvestigators measured the e-posure but did not assign it

non+e-perimental 2observational3

,ff t f 5i ti ti f S ki


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,ffect of 5icotine on cessation of Smoking

Source:JAMA 1994;271:595-600 32planatory variable' "icotine or placebo patch

?@ sub9ects /A@ in each group0

)esponse variable # outcome' Cessation of

smo*ing /yes#no0

RandomAssignment

4roup E

BD smokers

Treatment E

5icotine #atch

4roup C

BD smokers

Treatment C

#lacebo #atch

Yes

No

Yes

No
http://jama.ama-assn.org/cgi/content/abstract/271/8/595http://jama.ama-assn.org/cgi/content/abstract/271/8/595


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%nalysis of )C!

%nalyBed li*e cohort study &ith ))

ntention to treat analysis !!

Most conservative interpretation

nclude all persons assigned tointervention group /including those &hodid not get treatment or dropped out0

Subgroup analysis Groups identified pre-randomiBation


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Keas.res of Ris) in 0$ohort *t.dy2

Response to treat(ent

treat(ent R B

Les 6o

R A

a !

$ d

a I $ ! I d

a I !

$ I d

response ratea

a I !M

$

$ I d

a

Relati#e ris)Ea I !

$

$ I d


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,thics of ,-perimental Studies

,1uipoise + balanced doubtK canHt intentionallye-pose subjects to harm or "ithhold benefit

!nformed consent0 subjects must be a"are of study

objectives $eneficence0 must provide overall benefit to society

5on+malefficience 2onHt do harm3

Take care0 donHt deprive patients from kno"neffective treatment


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Strengths of cohort studies

Some evidence of causality.Lno" that predictor variable"as present before outcome variable occurred

irectly measure incidenceof a disease outcome

'an study multiple outcomes of a single e-posure 2RR ismeasure of association3

Smoking

' 'a lung

'a esophagus


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/eaknesses of cohort studies

,-pensive

!nefficient for studying rare outcomes

'ong. Anomalies and drug during pregnancy

'a pancreas and smoking

Often need long follo"+up period or a very large population

'AR!A

%oss to follo"+up& cross over can affect validity of findings

9ramingham


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Problems &ith cohort studies

Selection 2patients6control3 bias

Attrition 2rop out3

'o intervention

'ross over 8isclassification bias

'onfounders

!nformation bias

Recall bias

!ntervie"ers

#ublication bias


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*o" to guard against and deal "ith problems?

!horough identification of cases andcontrols

)andomiBation in )C!s

lindness in )C!s

Ese intention to treat analysis !!


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Temporal direction of study desi!ns

Lancet **+ 9:;8 ,-./1


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4ther Study !ypes


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Systematic Re0iews .Meta-

analyses

St d P id


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Study Pyramid

9est

Worst


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0rimes DA and Sc&ul 23 **' An overview of clinical researc&' 4ancet 5,67,-./1'


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3pidemiologic study designs

?hat type of study to chose depends onposure 2Study factors3

- Identify outcome factors 20ariables3


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#>ercise @)

Cryptosporidiosis is an enteric illness that isfreFuently &aterborne.

hala*dina and colleagues /;@@A0 could find nopublished studies of the ris* factors for

cryptosporidiosis in immunocompetent adults.

Patients &ith cryptosporidiosis &ere recruited from asurveillance system1 and age-matched controls &ererecruited by random-digit dialing.

Sub9ects in both groups &ere intervie&ed bytelephone to obtain information about previouse2posures


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Calvert EL, Hou!to" LA, Coo#er $, et al% Lo"-ter&


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, , # , 'rove&e"t '" (u"ct'o"al )y*#e#*'a u*'"

!y#"ot!era#y% +a*troe"teroloy 2002; 12: 177-5%

%CG)4E"D %MS' (e have sho&n hypnotherapy /H!0 tobe effective in irritable bo&el syndrome1 &ith long-termimprovements in symptomatology and Fuality of life /54I0.

!his study aimed to assess the efficacy of H! in functionaldyspepsia /JD0.

M3!H4DS' % total of :;? JD patients &ere randomiBed to H!1supportive therapy plus placebo medication1 or medicaltreatment for :? &ee*s.

Percentage change in symptomatology from baseline &asassessed after the :?-&ee* treatment phase /short-term0 and

after =? &ee*s /long-term0 &ith ;? H!1 ;K supportive therapy1and ;L medical treatment patients completing all phases ofthe study. 54I &as measured as a secondary outcome.


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(hat is the Study Design$

.!o&a* SH, S'le" /% E((ect o" )'a"o*t'c e(('c'e"cy o(


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, ya"ale*'a (or u")'((ere"t'ate) a)o&'"al #a'"% r J

Sur 200; 90:5-9%

!he Fuestion of &hether it is safe to provide analgesia forpatients &ith undifferentiated acute abdominal pain is mar*edby longstanding controversy over the possible mas*ing ofphysical findings.

!he goal of this revie& is to assess the pertinent studies.

% Medline search &as performed in %pril ;@@;1 using the termsanalgesia1 abdominal pain1 acute abdomen and morphine.

4ther articles &ere identified using the bibliographies of papersfound through Medline.

%ll articles reporting clinical trials of analgesia and its effects on

diagnosis or physical e2amination &ere revie&ed.


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% revie& that is conductedaccording to clearly stated1 scientificresearch methods1 and is designed to

minimiBe biases and errors inherentto traditional1 narrative revie&s.

Margaliot1 Nvi1 evin C. Chung. Systematic )evie&s' % Primer for Plastic Surgery)esearch. P)S Oournal. :;@# /;@@0

(hat is a Systematic )evie&$

(hat is the significance of


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(hat is the significance ofSystematic )evie&s$

!he large amount of medical literature reFuires clinicians

and researchers ali*e to rely on systematic revie&s in

order to ma*e an informed decision.

Systematic )evie&s minimiBe bias. % systematic revie&

is a more scientific method of summariBing literature

because specific protocols are used to determine &hich

studies &ill be included in the revie&.

evin C. Chung1 MD1 Patricia . urns1 MPH1 H. Myra im1 ScD1 Clinical Perspective' % Practical Guide to Meta-%nalysis. !he Oournal

of Hand Surgery. 6ol. A:% "o.:@ December ;@@?. p.:?:

M t % l i


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Meta- %nalysis

Meta-analysis is a statisticaltechniFue for combining the resultsof independent1 but similar1 studies

to obtain an overall estimate oftreatment effect.

Margaliot1 Nvi1 evin C. Chung. Systematic )evie&s' % Primer for Plastic Surgery)esearch. P)S Oournal. :;@# /;@@0 p.:QK@

M t % l i / t 0


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Meta- %nalysis /cont.0

(hile all meta-analyses are based onsystematic revie& of literature1 not allsystematic revie&s necessarily include

meta-analysis.

Margaliot1 Nvi1 evin C. Chung. Systematic )evie&s' %

Primer for Plastic Surgery )esearch. P)S Oournal. :;@# /;@@0p.:QK@

Junnel Plot


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u e o

8A funnel "lot is used as a way to assess "u9lication9ias in meta.analysis':

% Jorest Plot


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% Jorest Plot

types, architecture and hierarchy of research studies

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