Research 3rd lecture Sun. 9.10.2011 Dr.

Ashraf Shaweesh The doctor started this lecture by notifying us that this is the 4th week and we are still on the first concept, as we didnt know that before!!!! This lecture is a continuation of the previous two lectures, and we are going to complete talking about Basic Principles of research design and this lecture will cover the slides from 20 to the last slide which is 36. Now here is a little note for our colleagues who dont understand Arabic very well, dont worry as every single word in Arabic was translated to English, at least in this part of the lecture, Im sure most of you didnt understand this lecture because most of the time the doctor was explaining things in Arabic, so dont panic, it is a very nice and easy lecture....... So lets start, Slide no.20 Last time we talked about Bias, we identified bias and we said that we have three types of bias; the selection bias which is usually committed during the selection of the sample, and we gave an example that if you want to examine dental caries among people of different age groups, if you want to do a research on caries the sample should be consistent to the same age group, so you have to examine people belonging to the same age group like for example school children, you cant incorporate people who are older like young adults or adult people or old people, in this case you will have selection bias, because each age category has its own mares, for example when

we grow older the trans-occurrence of caries decreases in that type if you dont pay attention to the selection of your samples this may lead to a selection bias. Slide no.21 Measurement bias, if you want to examine dental caries both visually and radio graphically, the identification of caries clinically is different from the identification of caries on a radio graph, thats why if you want to do a research either you do all the research on clinical examination or on radio graphical examination, but you cant mix both of them otherwise you will have what we call measurement bias. Slide no.22 And Finally the confounding bias, we will give some examples for example people who take folic acid where found to have lower rate of colon cancer, but at the same time people who take folic acid usually they take multi vitamins, thats why they are careful about their health, so they are health conscious about diet and exercise, thats why may be they did not have colon cancer or they have decreased rate of colon cancer because they are aware about their health and not because they take folic acid alone, so thats why here is what we call the confounding bias, when we have a relationship between two factors and a third factor interferes with this relationship, for example you want to examine the effect of people who work in the mine the effect of coal on lung cancer but you didnt control for smoking, because it is possible that in the sample that you selected people who had lung cancer where heavy smokers and not because they work at the mine, so that is why it is very important that you identify the confounding factor. Slide no.23 A variable is not confounded if it is directly along the path from

the cause to effect; if you identify a factor and another factor and if you identify the ratios between these two factors when the relationship is the same from the beginning to the end and we dont have any other factor that affect this relationship then we say that the variable is not confounded, again another example; you want to measure the effect of smoking on lung cancer, in this case what you did in your research is that you collected a sample of smokers and you studied the existing of lung cancer in these people, in this way you control all other factors, so we dont have any confounding factor, the only possible cause of lung cancer in this group that you selected is smoking only, so in this case we say that the variables are not confounded. A confounding variable is not necessarily a cause itself, may be related to the suspected cause and the effect in an instance but not related in nature; a confounding variable is not all the time a cause of the problem itself, it can be associated with the problem, for example education and/or an income with good health, it sounds that educated people have good health, but at the same time people with high income also have a good health, so if you want to do a research it is very important to control for the effect of education and for the effect of income, we cant so do them together, we said usually education is associated with good health, but education is not the cause of good health, because we have other factors affecting the good health. Slide no.24 Selection bias is an issue in patients selection for observation, and so it is important in the design of the study; so selection bias usually occurs in the selection of the sample, thats why it is very important when you design your study to identify any possible selection bias and try to avoid it; the selection bias is very important in the phase of selection of the sample, thats why we can identify the bias that is related to the selection

selection bias at the beginning or at the design of the study, and you can avoid it. Slide no.25 The confounding bias is an issue in the analysis of the data, the confounding bias appears with you after you did the experiment, when you are doing the analysis of the results, you find that there is an effect of a factor, that you didnt notice or think about it before, thats why you need now to justify, now once the observation have been made; we did the observation and we did the measurements and everything, and when we about to write our research we find that there is a confounding factor, thats why in such a case you have to identify the confounding factor, and now you already did your research, that means it is difficult now to avoid it, so now what you can do is to try to explain that the confounding bias didnt give us a very bad results, may be your sample was very huge or very large, so that the effect of the confounding bias wasnt that much and didnt have that impact, and here is an example of a research I did myself, and I think may be all of you know it, which is timing of tooth eruption among the Jordanian population, because it was cross sectional study we didnt see the effect of the premature loss of deciduous teeth, we know that the premature loss of the deciduous tooth - if it falls before the normal age for it to fall may accelerate the eruption of the permanent tooth, and because my study was cross sectional; so it was difficult to know the children who have their deciduous teeth lost before their normal time or the children who have their deciduous teeth lost in the normal time, that happens because it was cross sectional and not longitudinal study, now that is considered as a confounding bias, but in the end when I published the research, I used a big part of the explanation in the discussion of the research to explain that those children percentage was very

small, and the research was on 3000 child, so the effect of the confounding factor if it exist will be very small, and not that big to think about it, thats why again if the confounding bias is not controlled, but when you write the research or when you analyze the research you have to explain to the reader that the effect of this confounding factor was not that big. Slide no.26 Often in the same study more than one bias operates, it is not all the time that we have only one bias, sometimes we have more than one bias at the same time. A distinction must be made between the potential for bias and the actual presence of bias in a particular study, you have to have the ability to identify the bias or to feel like there is an effect of that bias, the bias does not always appears strongly, sometimes the bias is potential, thats why you have to distinguished between the potential for the bias and the actual presence of the bias in a specific study. Slide no.27 Dealing with bias, if you want to deal with bias you have to identify the bias, and you have to measure the potential effect of bias, thats why you have to know its effect as well, to know for example if the effect of the bias is very big, because that may ruin the whole study, so that the whole study that you did is wrong, but sometimes if your sample is very big, and the effect of bias is small you can proceed in your research, but you have to explain in the discussion in your writing that I could control the bias or the effect of bias was not that big. Sometimes we tend to modify the research design when the potential effect on the result is big; sometimes we may change the design of the whole research when we feel like there is a potential for bias, for example I was going to do a research on the dental caries measuring it clinically and radio graphically,

but when I see that there is a measurement bias I change the whole research and make it just a clinical examination and not a radio graphical examination. Changing the conclusions in a clinically meaningful way when the effect is not big enough; when the effect of the bias is small, for example like that in my study about timing of tooth eruption and the effect of the premature lose of the predecessor teeth, because I constricted or I found that the effect of the premature lose in our community was not that significant or was not that big and the sample was very big, so that I justified and explained very well, but I didnt change the design of the study, that means when the effect is not that big you can change the conclusions or you can modify or you can explain the results in a meaningful way especially when the effect is not big. Slide no.28 Now lets talk about chance, which is another enemy - the researcher has two enemies; bias and chance -, we have already talked about bias, now lets talk about chance, Unbiased samples may misrepresent the population because of chance, as the chance effect increased as the sample is not representative of the population that you are doing your research on. Chance is the divergence of an observation on a sample from the true population value, as the measurement goes away from the true value that you want to measure. It is also called random variation, an example of that is tossing a coin 100 times; you have a coin and you want to toss it a 100 times, now the only possibility for it is to be either head or tail, so if I toss the coin 100 times, do I guarantee that the result will be 50 heads and 50 tails?, that is not necessarily; it may be 55 heads and 45 tails, now if I toss it 10 times only, is it necessarily for the result to be 5 heads and 5 tails? No, it may give for example 7 heads and 3 tails or 2 heads and 8 tails, so that as the number of tries

increases as the results be more accurate and more close to the correct value, thats why if I toss it a 1000 times, the results will be close to 500 heads and 500 tails, and if I toss it 10000 times, may be it will give around 5000 heads (a little greater for example) and around 5000 tails (a little lesser for example), so that the larger the sample size the lesser the chance, now what are the effects of chance?, it will affect in a way that I will not get the true value; now for this coin what is the percentage to have head or tail if I toss it only one time? It is 50%; it will be either head or tail, so that this is the true value or the actual observation, now when you do the research you want your sample to be representative of the true value, thats why you dont want the effect of chance, now what is the effect of chance?, it is that effect that will not give you the true value and that will give you another value, lets take another example; you want to do a research who is taller males or females?, now this is your research which is very simple, but I always give it as it is a simple example, now all of us know that males are taller than females, but now I can take 5 groups randomly from you and find that in 2 cases the females are taller than males, can I generalize this? No, it is not a rule. Now if I take just 2 groups (2 females and 2 males) and by chance the 2 females were taller than the 2 males, now can I say that females are taller than males just because of that? No, but if I take a sample of 100 person, the females who are taller than males in this sample may be 5 or 3, and if I take a sample of 1000 person, the number of the females who are taller than males will be lesser, so that the larger the sample size the lesser the chance, the chance is when I build my result on the chance, it is just a chance to find a female taller than a male, but it is not the true, the true is that males are taller than females and this is known, but by chance I may find in my study a female who is taller than a male.

*A student asked a question that it seems like how could I know the number of subjects in my study to control the effect of chance? and the doctor said that it is a very important question and that we will deal with that later on, but usually we have a rule that any sample should be representative at least if the subjects are more than 30, as the sample is more than 30 we consider the probability of the effect of chance to be minimized, so that I will never do a study on a sample less than 30, and as the number of subjects increases as it will be better, so the effect of chance is important to identify it from bias. Slide no.29 Chance verses bias, how to differentiate between the chance and the bias, bias distorts the situation in one direction or another, now in bias if the true value of some thing is for example 80, the bias may make it 70 or it may make it 90, but it is always in one direction either 70 or 90, but chance or random variation results in an observation above the true value as likely as one below it; the chance may make the value that you measure below or above the true value in the same percentage, that means if you have 50% of the probabilities above the true value you will also have 50% of the probabilities below the true value. Now I want to show you this figure - this figure is on Slide no.31 - : Now this is an example, if we want to measure the blood pressure by two ways; one way is by the means of Sphygmomanometer which is the device used to measure the blood pressure and we all know it, in fact this device does not give the true value of the blood pressure accurately, and the more accurate method of measuring blood pressure is by using intra- arterial canula by inserting the canula in the artery,

and this give us the blood pressure correctly 100%, so that it is more accurate to use the intra arterial canula than to use the Sphygmomanometer, now lets assume that you want to measure the blood pressure in a patient and the true measurement is 80, but when you use the Sphygmomanometer it is 90, and because you did a distortion of the true value in one direction we say that this is bias, we say that this is a measurement bias particularly, now here what does the chance do? the chance make the probability of taking the value to the right equals to the probability of taking it to the left, but it does not make a distortion in one direction only, while the bias makes a navigation of the sample to one side, but in chance we have the chance of having a reading above the true reading or below it, and the chance of having readings above and the chance of having observations below should be the same, that means that the chance always have something we call the random variation.

Now this is the end of the first part.

Done by: Raja Amin El-Haddad.

I dedicate this work to all my sweet friends, and of course I will not forget to thank you my lovely sister <<< 7abebti Ghada >>> Allah ye5aleli eyaki ya rab, o yeslamo kteer b3ref ene dayman m3albetic ma3e. Nadoooosh enti ya 3asal >>> thank you very much >>> you have a great impact on others >>> Allah yes3edek sho ennek btefhame !!!!

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Chance VS. Bias & relationship between chance and bias Slide #29+31 If you want to measure BP in a patient and the true measurement is 80 "the real value", and when use the sphygmomanometer it is 90 Because you made distortion of the real value in one direction; we said it is Bias "measurement bias" Now chance makes the value at the right equal to the value on left; but it doesn't make distortion in one direction. So bias makes distortion of the sample in one side, but chance may have readings above true reading or below the reading and chance of having readings above and the chance of having observation below should be the same! Bias distorts the situation in one direction or another chance always have the random variation, which results in an observation above the true value as likely as one below it.

? Q: not heard A:
" So the read of measurement from real value" 80" to the reading of sphygmomanometer 90 this drift is called Bias" "And the possibility of having below and above the 90; this is called chance" You should know how to distinguish between bias and chance ~The mean of many unbiased observation of a sample approximates the true observation of the population ~

When you take these different readings, there are many readings above the actual reading, or below the actual reading, but when you take the average of all of these readings you should have the actual reading, That means in chance when you take the average of all because you have some readings in the right side equal to other readings in the left side, finally average should be close to actual reading. ~ In small samples this may not be close to the true observation of the population ~ When the sample is larger, the probability of chance above and below the true observation would be equal For example, when throwing a coin a thousand time it is suppose to be 500 times head and 500 tail, (lama faradan nerme el 3omleh 1000 marrah lazm faradan etkoon 500 rasmeh 500 ketabeh) but it is possible to have an error of five times increase or decrease (zeyadeh aw noqsaan) in a 1000 times it is okay to have an error of 5 to 5 But when we shoot two or three times, it may be a possibility of head 3 times and tail 3 times, meaning that the effect of chance is big This means that the impact of opportunity here will be large, that is why the distribution of measurement to the right side and to the left side in the two values is the same; because you have a large sample, But when you have a small sample let's suppose that measures only twice, so the two values might be on the right side. But when you measure big samples, we have the probability of

having the value in the right side equal to the value in the left side. Bias VS. Chance Slide #30 ~ Bias can be prevented by proper conduction of clinical investigations ~ The bias can be prevented, but the chance cannot be prevented - Chance cant be eliminated, but can be reduced where it is possible to recognize the potential bias and therefore can be totally excluded But you cant cancel what you actually have (chance), for example some females are taller than males, "This is indeed" so the chance cant be eliminated but bias can be eliminated. ~ Bias can be corrected through proper data analysis ~ Sometimes especially confounding bias can be corrected when I make analysis of the data I can make corrections of bias "specially the confounding bias". ~ Its influence (the effect of chance) can be reduced by proper research "study" design ~, when you enlarge your sample for example the effect of chance becomes very reduced "y3ny 3nd e5teyar a huge sample the effect of chance will be decreased" ~ Statistics can be used to estimate the probability of chance or random variation ~, as we said before "statistics can calculate the probability of chance " In any research always the probability of chance must not be more than 5% , If it is more than 5%, it becomes the reality. So if you measure who is taller males or females, females who are taller than males by chance shouldn't be more than 5% "Doctor said eda ho 3ml ehsa2yeh 3la eltolab bel hall ; l2nh

3ddna 250 taleb , lazem ykoon fqt aql mn 25 talebeh atwal mn el male , otherwise he can't say females are taller than males" Systematic error VS. Random error Slide # 32 in any search you read you may find the words systematic error or random error *Systematic error is the error that results because of bias *Random error is the error that results because of chance. Always pay attention Sys error >> bias Random error >> chance. For example you did not control chance or did not reduce effects of chance, because of that you did not take enough number of subjects, for example when you study who is taller females or males you didn't take enough (proper) sample y3ni mathal bdl ma too5d 100 person a5dt fqt 5 and by chance kan 3 of females taller than males , so sample wasn't enough soooooo we have random error" " random error " the more the random error the less the validity of your research But the systematic error is because of bias, for example if you want to measure caries clinically by clinical examination of patients, you also included the radiographic examination, so you have an error; because in clinical examination of caries there is cases we don't see very well, but in radiographic examination caries would be clear, (as we are studying in cons) for example in class 2 caries can be seen in radiographs but in clinic it is not necessary to show. So when you use two different methods of measurement many different results comes out; this is called bias systematic error

~ Systematic error: Biases pushing the values of separate measurements away from the true value ~ ~ Random error: Even distribution about the true value ~ Always in random error the possibility of having higher or lower values are equal ~ various bias tend to balance each other out ~, when you increase the sample you will have increased probability of above or below becomes more the same more equal, so when we take the average to be very close to the true value (almost 100%) ~ Systematic error: Remains systematically different no matter how many times the measurement is repeated~ I mean even if we increase the sample the probability of bias remains found versa is possible to increase

Validity Slide # 33 Validity is called truth any research should be valid, the validity of the research is the truth of research ~ Validity is correspondence to the true value measured or searched for ~; Whenever the research gives results close to reality, we say it is more valid. ~ For an observation to be valid, it must be neither biased nor incorrect due to chance ~; the less of effect of bias and less the effect of chance >>> greater the validity.

So the enemies of any researcher are:

1) Chance 2) Bias If you could reduce the effect of chance and eliminate the effect of bias, then the values of your research are very valid and your research has high validity. We have two types of validity: 1- Internal validity 2- External validity Internal validity Slide # 34 The internal validity ~ is the degree to which the result of a study are correct for the patients being studied ~ The internal validity: the results of the research of a sample must be true for the sample itself ~ Internal: means it Applies to the conditions of the particular group of patients being observed and not to others ~ ~ Is determined by how well the design, data collection and analyses are conducted and threatened by bias and random variation ~ always which determines the internal validity is the biases and random variation or effect of chance . ~ Necessary but not sufficient by itself ~, that means we need to have the external validity

 , External validity" For example: Dr. Ashraf did a study on the timing of tooth eruption among Jordanian population, the data that he share should be apply on the sample that he collected this called internal validity, at the same time if he study timing of tooth eruption on another sample, then the result should be same, otherwise there is no external validity External validity Generalizability Slide # 35 the external validity which is also called "Generalizability" Y3ni the results of your research should be valid on other samples of the population and the whole population. ~ Is the degree to which the result of an observation hold true in other setting~ And the external validity means real results for a sample of each other or all population bm3na 25r: (in other words) if you take another sample from the same population, the values should be the same, and if you take the population also the values should be same, so this is called external validity " " ~The answer of : Assuming that the results are true in other settings, do they apply to my patients as well?~ )

 generalizability ( ~ Generalizability assumes that patients in a study are similar to other patients ~, that means if the Dr. does the study again, he will assume that the patients in his new research should be the same as the patients in his previous research. ~A study with high internal validity may be misleading if its results are generalized to the wrong patients~ The internal validity not enough by itself, there should be external validity as well. - But always the starting point should be internal validity. We cannot have external validity if we did not have internal validity; we cannot say that the results of the research real if they were not true on the sample itself
All patients with condition of interest

Internal validity

sampling sample sample

patients

A Selection bias

population

? ?

Measurement & confounding bias

chance

External validity Generalizability

Conclusion

This picture is a representation or a summary of what weve been talking about for the validity We have sample which is divided into A and B if we have any bias at this stage of selection of sample we call it selection bias Then we want to measure the sample, so if we have any bias during the measurement or during the analysis we call it measurement or confounding bias The chance plays the role after you measure your sample, it is possible that we have the effect of chance and then we have the conclusion. If the sample you studied is representative to another sample we call it is external validity. That means if the conclusion that results from your sample can be applied to another sample, or can be applied to another group of patients, or can be applied to all the population; then we say the research is of high validity externally or high generalizability.

And thats it forgive me for any mistake Good luck to all ^_^