Australian Medical Sheepskin

ARA0103 Aðferðafræði Rannsókna

Fyrirlestrar 7 og 8 Experimental design I/Tilraunasnið I quantitative/megindlegur 01/05/2020 Dr Andy Brooks 1

Dæmi...

What is the problem?

Hvað er vandamálið?

fyrst skref í rannsókn • Long term patients with bedsores.

Langtímasjúklingar með legusár.

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What are the variables?

Hverjar eru breyturnar?

• Independent variables: Óháðar breytur: – Bed mattress in use./Rumdýna í notkun – Frequency of patient turning.

– Time in hospital.

• Dependent variables: Háðar breytur: – Number of pressure ulcers./Fjöldi legusára – Patient comfort.

• Using a sheepskin mattress cover might make the patient too hot.

Athugasemd: in student projects, start by considering only one independent variable and one dependent variable.

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What is the intervention?

Hvað er inngrip?

• Medical Sheepskin… – http://www.healingfibres.com/ – – http://www.medicalsheepskins.com/index.html

http://www.classicsheepskin.com/medical.htm

• 2x frequency of patient turning/tvöfalda tíðni • Education/Menntun...

– If you can move yourself, change position every 15 minutes. – Eat properly/Borða rétt – ...

• Use pressure relieving supports...

olnbogi ökkli 01/05/2020 Dr Andy Brooks 4

Að bera saman gögn...

• Applying an intervention may be unnecessary if you can compare data from different wards/deildir, hospitals/sjúkrahús or nursing homes/hjúkrunarheimili.

gögn hér More turning of patients?

01/05/2020 gögn hér Dr Andy Brooks gögn hér Less turning of patients?

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dæmi State the null hypothesis H 0 Tilgreina núlltilgátuna H 0 áhrif er ekki til • A sheepskin mattress cover has no effect on the number of bed sores.

• Doubling frequency of patient turning has no effect on the number of bed sores.

• Educating patients on how to prevent bed sores has no effect on the number of bed sores.

01/05/2020 Usually endeavour to reject the null hypothesis.

Yfirleitt er leitast við að hafna núlltilgátuna.

Dr Andy Brooks 6

dæmi State the alternative hypothesis H a Tilgreina hin tilgátuna H 0 áhrif er til • A sheepskin mattress cover reduces the number of bed sores.

...minnkar fjöldi legusára • Doubling frequency of patient turning reduces the number of bed sores.

• Educating patients on how to prevent bed sores reduces the number of bed sores.

Ef þú ert að nota t-próf, til dæmis, vonin er að segja: núlltilgátan er ekki rétt, frekar hin tilgátan hlýtur að vera rétt.

hin tilgátan = aðaltilgátan 01/05/2020 Dr Andy Brooks 7

Select measurement tools Velja mælitæknar

• Hjúkrunarfræðingur getur lagt saman legusár beint.

• Rannsóknarmaður getur lagt saman legusár að nota myndir sjúklings.

• Hjúkrunarfræðingur getur mælt hita sjúklings.

• A questionnaire can be used to assess patient bed comfort.

– rannsóknarmaður má skrifa sjálf – eða nota/breyta spurningalista sem er til hjá t.d. http://www.medalreg.com/ , … 01/05/2020 Dr Andy Brooks 8

mælitæknar Validity Réttmæti • Measurement tools are reliable if you get the same answer by repeating the measurement.

– A nurse might fail to count a Stage I bed sore on one ankle which was counted by another nurse.

– Procedures have to be followed to measure blood pressure reliably.

• Measurement tools are valid if they measure what you want them to measure.

– On a questionnaire, patients may say they are too hot, but their temperatures measured using thermometers suggest they were not too hot.

• Maybe they completed the questionnaires on a very hot sunny day?

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Is the intervention potent?

Er inngrip sterkur?

• A sheepskin mattress cover that is too thin might not work.

• A video showing someone die in the final stages of smoking-related lung cancer is a more potent intervention than an information leaflet/bæklingur.

• Toe-grasp training for 30 seconds every month is unlikely to improve balance.

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Pilot study/Forathugun,Forrannsókn

• If possible, conduct a pilot study with a small number of people beforehand (4-6).

• Pilot subjects should be similar to the subjects in the actual experiment.

• Pilot studies check on: – Wording of questionnaires/Orðalag spurningalista.

• How often are patients turned?

– Aldrei Stundum Oft Mjög Oft • Hvað þýðir stundum, oft, og mjög oft?

– Unclear instructions/Óvissar leiðbeiningar.

• How often should the sheepskin mattress cover be washed?

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confounding variable/truflandi breyta

Use a control group Nota samanburðarhóp

• The control group do not receive the intervention.

• From an ethical point of view, the control group should receive normal treatment/venuleg meðferð.

• Using a control group is the only way to deal with confounding variables.

– age, sex, weight, surgery, mobility (gangandi?), ...

• Patient characteristics in the control group should be similar to the intervention group.

– Gengur ekki að bera saman 20-25 ára með 70-75 ára...

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R

andomized

C

ontrolled

T

rial hrein tilraun slembi íhlutunarrannsókn Identify eligible subjects eligibility criterion/ úrtaksskilgreining Obtain informed consent/Afla upplýsts samþykkis overview/yfirlit Willing Þátttakendur Unwilling Non-participants

How many unwilling?

Randomization/Tilviljunarval Intervention group (I) Control group (C)

between subjects/ milli hópa

Participants Drop outs Þátttakendur Brottföll Data collection

Number of bed sores

Data collection Safna gögn

How many drop outs?

Number of bed sores

Safna gögn

How many drop outs?

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Randomization/Tilviljunarval

• Ideally, a third party allocates subjects to the control (C) or intervention (I).

– Called allocation concealment/Kallað leynd úthlutunar.

– Avoids experimenter bias/Forðast áhrif tilraunamanns • An experimenter could allocate younger patients to the sheepskin group (I).

• An experimenter could allocate only post-operative patients to the control group (C).

• Subjects can be given a number and numbers can be selected at random using a computer program.

http://www.graphpad.com/quickcalcs/randomize1.cfm

Dr Andy Brooks 14 01/05/2020

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Randomized Controlled Trial (RCT)

overlap/skörun Inngrip Samanburðahópur Inngrip tíðni tíðni Samanburðahópur • • > fjöldi legusára Obvious that the intervention reduces the number of leg sores. A t-test is not needed.

Auglóst að inngrip minnkar fjöldi legusára. t-próf er óþarft.

• • > fjöldi legusára A t-test is needed. Is p < 0,05? If so, the difference is statistically significant and the intervention reduces the number of leg sores.

t próf er þarft. Er p-gildi < 0,05? Ef svo, mismunurinn er tölfrælega marktæk og inngrip minnkar fjöldi legusára 01/05/2020 Dr Andy Brooks 16

sample size/úrtaksstærð

Within subjects design/Innanhópasnið

• Single subject/einn þátttakandi úrtaksstærð n=1 AB design/AB snið.

Leggja saman legusár.

Fyrr (A) og á eftir (B).

Ekki hægt að nota tölfræðipróf, svo er ekki hægt að álykta um þýði.

Líka ABAB, ABABAB snið.

A B • An individual patient may be so unique and in need of such help, that only they receive the intervention.

01/05/2020 Dr Andy Brooks Dr House...

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Within subjects design/ Innanhópasnið

imbalanced/ ójafnvægt Subject/Þáttakandi mars (C) apríl (I) n=10

S1 control sheepskin

S2 control sheepskin S3 S4 S5 S6 S7 S8 S9 S10 control control control control control control control control sheepskin sheepskin sheepskin sheepskin sheepskin sheepskin sheepskin sheepskin “paired” or “related” or “dependent” data > nota parað t-próf 01/05/2020 safna gögn lok mars og lok apríl 18

What if ?/Hvað ef?

• During the control period in March, there are nursing staff shortages and patients are turned only 50% of the time. – This would effect the measurements of bed sores at the end of the control period. (skekkja) • This within subjects design is said to be imbalanced and is fatally flawed.

– gengur ekki að nota slíkt snið 01/05/2020 Dr Andy Brooks 19

cross-over

Within subjects design/ Innanhópasnið

balanced/í jafnvægi Subject/Þáttakandi Mars (C) Apríl (I) n=10 S1 control

sheepskin

S2 S3 S4 S5 S6 S7 S8 S9 S10

sheepskin

control

sheepskin

control

sheepskin

control

sheepskin

control

sheepskin

control

sheepskin

control

sheepskin

control

sheepskin

control

sheepskin

control safna gögn lok mars og lok apríl 20 01/05/2020

Within subjects design/Innanhópasnið

advantage/kostur • By using the same subjects, there is better control of variability between subjects.

• But sometimes it is impossible for subjects to receive both the control and the intervention.

– Post-operative patients can be measured only once. They are no longer post-operative after receiving either the control or the intervention.

01/05/2020 post operative/eftiraðgerðar Dr Andy Brooks 21

Within subjects design/Innanhópasnið

• Sometimes the cross-over design leads to ethical problems.

siðfræðilegt vandamál

– If the intervention works really well for an individual patient, should they be taken of the intervention and put on the control ?

• Gengur ekki að hætta að lækna að nota inngrip!

• Patients are no longer blinded.

Sjúklingar eru ekki lengur blindir.

– They can realise that the use of the sheepskin matress cover is the intervention.

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Within subjects design/Innanhópasnið

ójafnvægt

• Sometimes the cross-over itself is imbalanced.

– Going from a sheepskin to a normal mattress is not the same as going from a normal mattress to a sheepskin.

• Sometimes a patient´s health status can change over time.

heilsuástand breytast yfir tíma...

– Becoming post-operative as you are about to cross over between control (C) and interventiion (I).

– Data for such patients may have to be left out.

• Data cleansing/Gagnahreinsun • Deletion or drop-out/Brottfall 01/05/2020 Dr Andy Brooks 23

Between

subjects design/

Milli

hópasnið.

Dæmi

Regarding diastolic blood pressure, is there a statitiscally significant difference between men and women?

Varðandi blóðþrýsting, er tölfræðilega marktækur munur til á milla manna og kvenna?

Men

76, 76, 74, 70, 80, 68, 90, 70, 76, 80, 68, 72, 96, 80, 90, 72

Women

76, 70, 82, 90, 68, 60, 62, 60, 62, 72, 68, 80, 74 Perform an independent t-test (2-tailed, unequal variances).

Reiknaðu óparað/óháð t-próf (tvíhliða, ójafnar dreifingar).

What is the significance level?

What is the effect size?

__________ (hvað er marktektarstig?) __________ (hver er stærð áhrifa?) The null hypothesis/Nulltilgátan: “There is no difference in diastolic blood pressure between men and women.” “Munur á blóðþrýstingi er ekki til á milli manna og kvenna.” 01/05/2020 Dr Andy Brooks 24

Equal sample sizes is better.

Jafnar úrtakstærðir er betri.

t-Test: Two-Sample Assuming Unequal Variances Mean Variance Observations Hypothesized Mean Difference df t Stat P(T<=t) one-tail t Critical one-tail

P(T<=t) two-tail

t Critical two-tail

Variable 1

77,375

69,71666667 16 0 25 1,907486345 0,034004546 1,708140745

0,068009092

2,059538536

Variable 2

71,07692308

85,07692308 13

null hypothesis the value of t

p-gildi 01/05/2020 The value of p needs to be less than 0,05 for statistical significance.

p gildi < 0,05 þýðir að munur er tölfræðilega marktækur. Dr Andy Brooks 25

power of a statistical test/styrkur tölfræðiprófs

more subjects?

fjölga þátttakendum?

• p gildi er ekki minna en 0,05 en er lítið (0,07).

• Munur á milli meðaltala er 6.

• If there were more subjects, it might be possible to detect a real difference.

• A negative result in a statistical test might be because you do not have enough subjects. The statistical test might not have enough

statistical power

to detect the difference between means.

• What if we have another set of measurements of diastolic blood pressure that are similar to the first?

– Is it possible to obtain statistical significance?

Er hægt að ná tölfræðileg marktekt?

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power of a statistical test/styrkur tölfræðiprófs

How many subjects?

Hve margir þátttakendur?

• Ef þú ert að reikna út meðaltal og staðalfrávik, úrtaksstærð n hlytur að vera >=10. (segir Andy) • n>=20 er betri • n>=30 er ennþá betri.

• The greater the number of subjects the greater the statistical power.

n>=30 meiri styrkur Dr Andy Brooks 01/05/2020 27

afköst Dæmi fjöldi í hverju hólfi sniðsins • Ef n = 10, líkur á því að finna mun (sem er til) er ≈0,3.

• Ef n = 20, líkur á því að finna mun (sem er til) er ≈0,6.

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Standard error of the mean Staðalvilla meðaltala

• The standard deviation of the sampling distribution of the sample mean is called the standard error of the mean.

Staðalfrávik úrtakadreifingar úrtaksmeðaltals kallast staðalvilla meðaltal.   x  n The standard error of the mean gets less with a bigger sample.

Staðalvilla meðaltala minnkar með stærra úrtaki.

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RVLS Sampling Distributions normaldreifing

σ=5,00

þýðisstaðalfrávik 5 5  2 , 24

S=2,27

staðalfrávik úrtakadreifingar 01/05/2020 Dr Andy Brooks

n=5

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RVLS Sampling Distributions normaldreifing

σ=5,00

þýðisstaðalfrávik 5 10  1 , 58

S=1,54

staðalfrávik úrtakadreifingar 01/05/2020 Dr Andy Brooks

n=10

31

RVLS Sampling Distributions normaldreifing

σ=5,00

þýðisstaðalfrávik 5 25  1

S=1,02

staðalfrávik úrtakadreifingar 01/05/2020 Dr Andy Brooks

n=25

32

skewed/skekkt parametric test/stikapróf non parametric test/stikalaust próf Central Limit Theorem/Markgildissetningin

n=25

• • Even if the population distribution is skewed, the sampling distribution of means is normal if the sample size n is large enough.

If the population distribution is skewed and the sample size is small, you must use non-parametric statistics. These tests have less statistical power. The equivalent of the parametric independent t-test is called the

Mann Whitney U test

.

01/05/2020 Dr Andy Brooks 33

Diabetes/Sykursýki http://dtc.ucsf.edu/ Diabetes Teaching Center

Within

subjects design/

Innan

hópasnið

Dæmi

Does diabetes education improve scores on tests about diabetes knowledge?

S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 Before Fyrr After Eftir 75 77

62 65 67 68 70 72 55 62 59 61 60 60 64 67 72 75 59 68

paired

or

related

or

dependent

t test/parað t-próf Perform a paried/related/dependent t-test (2-tailed).

Reiknaðu parað t-próf (tvíhliða).

What is the significance level?

__________ (hvað er marktektarstig?) What is the effect size?

__________ (hver er stærð áhrifa?) Null hypothesis/Nulltilgátan: “There is no difference in scores after a course about diabetes.” “Munur á stigafjölda er ekki til eftir nám um sykursýki” 01/05/2020 Dr Andy Brooks 34

t-Test: Paired Two Sample for Means 6 , 42 , 23  6 , 5 5 / 10  2 Mean Variance

(s 2 )

Observations Pearson Correlation Hypothesized Mean Difference df t Stat P(T<=t) one-tail t Critical one-tail

P(T<=t) two-tail

t Critical two-tail

Variable 1

64,3 42,23333333 10 0,906845904 0 9 -3,692307692 0,002489772 1,833112923

0,004979545

2,262157158

Variable 2

67,5 33,61111111 p gildi 10

null hypothesis

p gildi/marktektarstig er minna en 0,05. Við höfum tölfræðileg marktekt.

01/05/2020 Dr Andy Brooks 35

A two-tailed or one-tailed t-test?

Einhliða próf eða tvíhliða próf?

• Diabetes education will not decrease peoples’ knowledge about diabetes.

– Í nám, þú lærir eitthvað...

• We can use the one-tailed t-test result.

– The value of p is 0,00248.

• statistically significant/tölfræðilega marktæk 01/05/2020 t=-3,69 Dr Andy Brooks 36

Clinically significant effect?

Klínísk marktæk áhrif?

• The paired t-test result (one-sided) showed that diabetes education improves knowledge about diabetes.

• En áhrifastærð er aðeins 3,2%.

• Er það klínísk marktæk?

• Do patients control their blood sugar levels better as a result of only slightly improved knowledge ?

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Statistical significance does not imply clinical significance • Reducing the mean number of bed sores by 1,0 means one less bed sore for every patient.

– Að meðaltali og er klínísk marktæk • Reducing the mean number of bed sores by 0,1 means one less bed sore every 10 patients.

• Reducing the mean number of bed sores by 0,01 means one less bed sore every 100 patients.

• Reducing the mean number of bed sores by 0,001 means one less bed sore every 1000 patients.

– áhrifastærð er ekki klínísk marktæk tölfræðilega marktæk er ekki sama sem klínísk marktæk 01/05/2020 Dr Andy Brooks 38