 very good morning all so let's continue our epidemiological classes so today I will be explaining about the experimental study design so we were seeing the observational study design so far in our last two classes so it was descriptive and analytical now let's move on to the experimental study design so the fundamental difference between descriptive and experimental study design is the investigator has a significant role in experimental design he is not observing the research instead he is actively participating or he is intervening the research or is manipulating the research not manipulating in the sense in any other sense manipulation means he is actively putting some trek into the research or he is withdrawing something which they were constantly doing so the active participation of the investigator or researcher is the fundamental feature of experimental design which is not seen it descriptive study because the descriptive study it is observing the details of the groups either it is a case group or control group or a cohort group and noting the details will give you the hypothesis testing under my control trial or experimental study the investigator has a very striking role that is the best study design you can say that it is the best study design to test the hypothesis but to the last examples like for poison and the smoking and lung cancer in those cases we cannot do an experimental design because it is very unethical to create a group with smoking or create a group with street food so there the only possibilities case control or cohort study that we can do only observe it but and truck trials or any other efficacy trials relating to new missionaries or any new tricks in these cases we can do an experimental study design because the ethical issue is very crucial in experimental design so this take an example it is a five milligram of a new trek we are checking whether it will reduce the pain in cesarean patients compared to the existing lack of neck so in this case we are checking efficacy of any trip so this is the basic setup for an experimental study design comparison by new tricks or any other new two methodologies whereas in disease cases we cannot do an experimental design because we cannot do an intervention with a disease cannot create the disease and do an experiment that is unethically unethical and it is not at all feasible so mostly the disease scenario will end up at analytical study and it will not go to the experimental study design so we have to stop the testing of hypothesis at analytical study let's be a case control cohort but this type of scenario we can do an experimental study so this is checking two tracks efficacy a new drug invented is it good or bad compared to the existing duck so the common design is same for all there will be testing hypothesis always need a comparison group so in experimental study design the population we will divide into two groups and we'll check the outcome after a period of time the one group will be test group where the new drug will be allowed and a group to where the existing drug will be allowed so this new treatment and control treatment allocation or intervention or manipulation is a fundamental part of almost unique part of experimental study which was not there in the descriptive study designs and after a period of time we'll check the outcome and we'll compare the outcome and we can say that which drug is good and which drug is bad so basically we have animal studies and human studies in experimental designs we know animal studies we might have heard about rats monkeys rabbits so all the tracks will be first tested in animals then only it will go to the humans how unethical to conduct the experiment in animals it is a matter of question but for the sake of human safety we need to sacrifice animals that's what it's what the only possible way to test the efficacy if it trick so first it will be tested in animals and if it is found to be efficacious then the study will be moved to humans and humans also it will go step by step first the sample will be very low maybe 5 10 then it will go to 100 and it will reach 1000 and there will be surveillance trial then it will come to the market if it is proven to be efficacious even in the surveillance that is stage 4 122 type 4 so few examples we'll see how this experiment was done by James Flynn was the first one of the first experimental studies in the science so he was a naval doctor used to go with the Navy's Navy ships so what happened in January was many sailors were affected with one disease known as curvy that affects gums which was caused due to deficiency of vitamin C so till that time there was no treatment for scurvy so what it was he arranged the participants into six groups and he was giving different different reagent for each group and one among was alive so these sailors were later known as slimes so what happened was people the group were getting lemon and were covering in two to three days compared to other groups other groups were not required properly during the study period so he found out that the agent within the lemon could cure the curvy disease so this was one of the first experiment happened in science so then the smallpox experiment by Edwardian he invented smallpox vaccination so this was it was believed that during his time people who are infected with the cow box is known to be having immunity against smallpox infection so it was believed that in those times so he wanted to experiment on it so what he did was he took a small pus from the lesion of a cowpox which was his maid was originally infected with cowpox so he took small lesion from the cowpox lesion a small pus he took from the cowpox lesion and injected into a boy he made a wound and injected into it in one week period after this inoculation the boy was having symptoms fever and other symptoms but after one week he was completely recovered he found out that the boy got the immunity then again to check whether he got immunity against smallpox again he inflated a lesion and a specimen collected from the smallpox lesion and injected this solution to the boy but the boy was not having any smallpox disease and he found out that the boys got smallpox immunity by inoculating copoxulation that was a landmark study and which created the vaccination so this was Edwardian did it in 1796 so smallpox now smallpox is completely eradicated from just like polio so these were experiments done by scientist so we'll go to the experimental design the true experimental design is randomized controlled trial don't get confused with root canal treatment this is a randomized control trial that is the true experimental design experimental means we do an experiment not just observing the James Lynn did experiment he gave he intervened with lime water the gender intervene with the inoculation copox lesion but in descriptive study there was no role from the investigator was just observing so the experimental study designed the true design is randomized control for two experiment we were seeing just now that not randomized control trial because randomized control trial means the group should be randomly distributed randomly allocated there was no randomization in both the cases it was just the pioneer experiments so nobody knew what is randomization nobody knew the necessity of randomization and the control means there should be a control for the comparison then only we can test the hypothesis so just like his control board study they have comparison group you also need to have a control group and this is the third letter T for trial so this is a trial trial means an experiment investigator is doing experiment so here in true sense a true experiment is RCT so in RCT the first letter that is patient will be randomly selected we can select non-randomly in James Lynn experiment it was non-randomly selected and we need to have a controller placebo group in James Lynn experiment all the other groups were getting in other than lime water where control kept it for comparison then they can prove it and intervention that is trial so these three letters indicate the true experimental study design there is randomized control trial the other one is quasi experimental design there is no randomization and there may not be control group so this is also an experimental design so we can say that all experimental studies not RCTs if it is to be RCT there should be a randomization of participant that is allocation into two groups and there should be a proper control then only it will become an experimental study anyway it is trial it is a non-randomized or randomized it is a trial because it's experimental design so basically we'll see the steps of RCT so the steps of RCT so these are the steps of RCT first we need to write a protocol we need to write it we need to submit it if it is study just planning to be conducted in India you need to get a proper approval from the trial registry clinical trial registry and also you need to get approval from ICMR at Indian Council of Medical Research others you cannot do a proper RCT even if you do it will not be published anywhere so first you need to make a proper protocol then you have to find a population where you want to conduct the study then from the population you need to take your sample population because the reference population will be very huge if you're doing a study on toothpaste effective toothpaste you are going as school to conduct a study entire school children will be your reference population so from the reference population you have to select a 50 or 100 students as your sample then you have to do the inclusion of an exclusion criteria that is you have to see whether they match your criteria whether they belong to the this age group whether they have this much carries or whether have these criterias if they are not matching with your criteria you have to exclude it so you get a sample then you have to do the randomization that is the most important part of clinical trial you have to randomly allocate participants into experimental and control group so you may take a cheat method or you may take a lottery that is random number method you have to allocate participant into experimental and control group then you have to do the manipulation or intervention that is giving toothpaste to each group that is different different toothpaste for you giving only one new toothpaste which you are trying to prove in one group and the existing group in other group and you have to follow up for a period of time depending upon the objective study and finally you have to do the assessment of outcome and you have to say that your hypothesis is true or false or you can say that this is efficacious than the existing one or this is not efficacious so this is the basic steps of an experimental study so let's see the protocol step that you need to write about aims and objectives what questions you are going to ask and the criteria or selection of your participants and sample size how much sample you need to collect and the procedure how you are allocating the subjects into two groups and what treatment you are applying and how you are applying and what are the procedures so all things you need to write in your protocol and this protocol is always helping us to prevent bias. The bias will be dealing in future classes so bias is something but error so it helps us to reduce the error okay second is a reference and experimental population so reference population as you all do it is entire school children and from the school children we select depending upon our sample size a small population that is our experimental population it depends upon the objective study so that's how this entire school children from that we select a few people as our population so it is derived from the reference population that is derived from the school children total school children so this is the population that is our sample population where the actual experiment is going to happen okay so now next what we do is we divide this sample population into study and control group by doing a process known as randomization so randomization is known as a hard control trial if you don't hold a randomization study will be less quality it will be inferior quality in a clinical trial so randomization it is a statistical procedure so you ask the participants to take a cheat from a box where you made if under participants hundred is your samples says you made hundred cheats in a box where 50 will be experimental and 50 will be reference or control group so each participants will come and take one cheat from the box and hand it over to you so you'll enter or your assistant will enter that student will go to which group the student will not be knowing so each participants will come and hundred participants will take one cheat so automatically 50 will go to the study group and 50 will be in the control group but the participants will not will not be knowing which group they are being allocated and that is known as a procedure it is a single blind so blinding and bias will come in later classes detail so now let's see the process is to eliminate a selection pass a selection pass bias error systematic error so passes nothing but which commonly seen in any search so we divide the group into study and control okay so that is done by atomization so it gives a confidence that the groups are comparable always the group should be comparable otherwise the study result is always flowed will not get the actual result okay so the like can be compared with the likes always is two participants will be comparable so it is assumed that if you do randomization the groups will be comparable there's no proof for it but it's believe that you do randomization the two groups will be comparable so what we are getting is by random allocation every individual gets an equal chance of being allocated either okay so each boy has that chance when until the moment he takes a treat he has a chance to be in the experimental or control so that is the heart of control so now the next part is manipulation so manipulation manipulation is we are if we are trying to find out the tooth brush efficacy in one group will give one type of toothpaste and another existing toothpaste and we ask them to brush many times and it should be followed up so we'll explain the procedure and we'll monitor it and we ask them to do the same procedure for a particular period of time this is known as manipulation or intervention this is the next step after so next step after randomization so third step is randomization second step is selecting reference population selecting reference population and sample population then we are dividing the sample population to study and control group then we are doing manipulation after manipulation you follow up so if they are using the toothpaste for two weeks of period then after two weeks you check the efficacy by checking using any indices any black indices or ginger indices you can check you have to check it before the study and after the study so the plot the problem which arises commonly in experimental studies attrition this terminology I had mentioned in the previous class that is loss to follow up you are starting the study with 100 people and you need to follow up and you need to get the data of 100 even after the study but some may not comply with their instructions and some may leave out of the study they have all authority to leave at any point of the time so you cannot blame the participants for not being adhering to the protocol so if they are leaving out of the study it might affect the power of the study so usually what researchers do is they increase the sample by 20 percentage expecting that 20 percentage might leave the study so if we increase the sample size it will not affect the power of the study at the end so after follow up so attrition is lost to follow due to inevitable factors such as death migration or loss of interest so finally we do the assessment we take the values and we compare with control groups and we find out which is better and which is bad okay so randomized control trial