Experimetal Studies

EXPERIMENTAL STUDIES RECAP: Types of study designs:

- Affords the most control over the study situation

1. Observational : observing participants. You cannot control participants.

- Enables the researcher to isolate the observed effec t of the exposure or intervention.

A. Descriptive 1. A .1. Case report/study - 1 case/disease 1. A .2.case series -many patients but same cases. If you ar e Looking for the commonalities and differences of Cases. 1. A .3. Ecologic study 1. A .4. Cross sectional

- Researcher chooses a study population without the outcome (like cohort) – usually the outcome is that the disease will diminished or the patient will have no disease. - eg. Occurrence of COPD with the smokers and nonsmokers. The characteristics of each group study are equal. And the only difference is that other gr oup are smokers and the other is not.

B. Analytic-observational:

b. 1 case control: - Case: patients who have the disease Control: patients without the disease Put back in time for the exposure. It is how many Case and control patients are exposed to the Diseases. b. 2 cohort: 2 groups of people (exposed and Unexposed, with factor or without factor)

- Assigns the subjects into two groups by scientific technique. - introduces the intervention intervention to one group and withhold it from the other. - sabihin natin 2 groups of people may hypertension. 1 group is given an intervention and t he other group not given intervention. When you assigned participants to the groups you do it by a scientific technique (randomization) two types:

eg. Smokers and non-smokers. Without COPD then follow-up over period of time. Then identifying incidence of COPD among smokers and non-smokers sample. We compare the incidence of the disease among the smoker’s vs the non -smokers and then look at the risk ratio (risk of acquiring disease of smoker’s vs nonsmokers) 2. Experimental Experimental studies - Called interventional study because we give an intervention. You intervene. - involves intentional change with some characteristics of the study participants. - eg. Introduction of a drug. You give an intervention.

- Provides the strongest evidence of causal re lationship of all the study designs compared to observational studies.

True experiments  – scientific technique, there is randomization in the allocation of treatment (assign the treatment to study part at random) Quasi- experiments- no randomization *random sampling and randomization is different. Randomization is random allocation of treatment. You assign treatment to participants at random. Like for example kayong lahat may sakit, HD. Each of you are assigned to take drugs by “picking from the box with 2 different kinds of drugs”. Random sampling means  pagkuha ng sample at random. For example 100 kayo I will pick only 70 from you at random. 1. True experiments: + Randomized controlled trials - Participants are randomly assigned to two g roups, usually 1 study grp (receive treatment) and 1 control grp (no treatment). - The study group receives a treatment, the control grp does not.

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EXPERIMENTAL STUDIES

Before the control group receives placebo for the treatment but now a days it is not given anymore because it is unethical to give a medicine that will not cure the patient. Only those disease that are less conflict or less extensive could have the placebo. Give a drug to the study group and give placebo to the control group with both groups having same lifestyle modification. Giving of placebo is justified.

- More commonly known as randomized clinical trial - normally conducted in 4 phases (1-4) - each phase is treated as separate clinical trial - drug discovery, drug development. Drug-development process will normally proceed through all four phases over many years. •

Phases of clinical trial:

- Treatment can be an experimental preventive or therapeutic procedure, maneuver or intervention. - Results are assessed by comparison of the outcome in the study group and in the control group. - With randomization you ensure the characteristics of the two groups are equal. When you a ssign participants at randomization you ensure that the participants in the 2 groups are of equal characteristics. That will only happened if the sample size is very large. Example: effect of a drug VS placebo Divide the study participants into two groups (1 group with placebo and the other is t he experimental drug) suppose that people given with the drug are younger than people receiving the placebo. The result shows t hat the study group receiving the drug has more number of cured patients as to the group of placebo who has no one or less number of cured patients. Will y ou say that the drug is effective? No, because the participants who took the drug are younger than that of those who took the placebo. For us to say that the drug is effective over the placebo then the characteristics of the participants of the 2 groups should equal. Randomized controlled trials:

1. Preventive clinical trial: used to test the effectiveness of a preventive measure. Eg. Vaccines 2. Intervention clinical trial : manages risk factors to prevent occurrence of disease for which a factor is known to cause. Eg. Smoking cessation program. 3. Therapeutic clinical trial : used to test the effectiveness of treatment drugs and procedures to arrest the disease problem. Eg. Drugs to cure the disease. Therapeutic clinical trial:

Phase1: - A single sub therapeutic doses of the study drug are given to a small no subjects (10-15) -normally given to normal or healthy subjects/patients. Usually males are the subject. - Gathers preliminary data on the drugs pharmacodynamics (what the drugs does to the body) and pharmacokinetics (what the body does to the drugs) - documents the absorption, distribution, metabolism, and excretion (ADME) of the drug. -not randomized controlled Phase 2: - tested with as small group of people 20-80 grp of people to evaluate the safety of drug. - determine safe dosage ranges and identifies side effects of drug. - A drugs side effects could be subtle or long term or may only happen with a few of people. -thus phase 2 trials are not expected to identify all side effects. Because it has only small group of people. -not randomized controlled Phase 3: -aimed to establishing the efficacy of the drug. Usually against placebo - tested with a large group of people (100-300) to see if it is effective and to further evaluate its safety. -the gradual increase in sample size allows for less common side to be progressively sought. (In larger subjects, the former few seen side effects will be shown in much larger side effects). - More commonly studied as a Randomized Controlled Clinical Trial

-Randomization is done in phase 3. The study group receives the new treatment or the drug. The control group receives an alternative treatment more commonly a placebo.

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EXPERIMENTAL STUDIES -The control group may also receive a standard treatment - blinding is usually done to prevent bias in the reporting of outcome Single blind: only the subject are unaware of the treatment they receive. *if the signs and symptoms of the subject is subjective. *in the informed consent, it should be indicated that they can either receive the placebo or the treatment drug. Except that the subjects do not know the treatment that they will be having.

Double blind: both the subject and the investigators or unaware of the treatment the subject are getting. *done when the examinations of the outcome is subjective, then that is the time that you blind the investigators. Phase 4:

-PMS post marketing surveillance/studies - serves as final confirmation of safety and efficacy - tested with large groups of people (1,000-3,000) to confirm is effectiveness, monitor SE, Compare it to commonly used treatments and collect information that will allow it to be used safely. *involve drugs that already in the market. Drugs approved in the country. We collect information about the marketed drugs and its efficacy.

2. Quasi-experimental design:

- No randomization in allocation of treatment -most community trials are done using this type of study design. (you cannot do r andomization in community trial study). Example: community trial - Test of efficacy of fluoridation of drinking water in preventing tooth decay

-Two comparable cities in New York State in 1940’s (Newburgh and Kingston) were compared for the occurrence of tooth decay and related dental problems in children -Newburgh received fluoride for about one decade and Kingston did not. -In Newburgh the incidence of dental problems decreased by about a half compared to the period prior to fluoridation -In Kingston dental problems slightly increased -This particular study utilized a quasi-experimental study since subjects (cities) were assigned the treatment arbitrarily and not randomly. Other classification of clinical trials A. by the study design: Parallel group - each participants is randomly assigned to a group, a d all the participants in the grp either receive or do not receive intervention. (Very much the same with the randomized controlled trial) Cross over- over time, each participant receives (or does not receive) an intervention in a random sequence. “In exchange”.

*1 group will receive the study drug, that randomized and the other group will receive placebo. Then you look out at the outcome. Compare the outcome. Wash out period (wash out the drug that are given para mawala sa effect sa system ng subject. Normally 5-7x the halflife of the drug). Then you crossover meaning you have grp A that receive the study drug ngayon receives the placebo. The group B that receives the placebo now will receive the study drug. B. by outcome: Explanatory or pragmatic Explanatory RCTs - test efficacy (strict inclusion and exclusion criteria) in a research setting with highly selected participants and under highly controlled conditions. Pragmantic RCTs - test effectiveness in everyday practice with relatively unselected participants and

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EXPERIMENTAL STUDIES under flexible conditions; in this way, pragmatic RCT’s can "inform decisions about practice”. *not much strict rules in inclusion and exclusion criteria. C. by hypothesis: - Categorized as Superior trials or noninferiorty trials Superiority trials  – experimental drug is superior to the placebo. *if you want to test a drug over a placebo more often than not it is a superiority trial.

-Most RCT’s are superiority trials, in which one intervention is hypothesized to be superior to another Non-inferiority Trials - which determines whether a new treatment is no worse than a reference treatment (Standard drug).

*if you want to test an experimental drug (less expensive than the standard drug) whether it is a comparable with the standard drug. Clinical trials (Randomized):

- can be likened to a cohort study (2grps of people. 1 is exposed and other 1 unexposed. Both no outcome/disease. Follow up ilan sa mga groups ang may sakit and ilan ang wala. And compare.) *unlike in cohort both groups have outcome/disease. Giving 2 different intervention (placebo or study drug) then follow up. Ilan ang may sakin parin with the groups then that is you’re RISK RATIO. - Measures called risk ration (RR), absolute risk reduction (ARR), relative risk reduction (RRR) and numbers needed to treat (NTT) - Calculation for RR is the same as that for the cohort study. Disease

No Disease

Exposed

a

b

Unexposed

c

d

a- with intervention still with disease

b- with intervention, did not have the disease (gumaling) c- placebo, with disease d- placebo no disease EER experimental event rate : no of events/disease in the experimental grp EER = A/A+B EER = with intervention but with disease/binigyan ng study drug

CER control event rate: no of events /dse crisk in the control grp

CER= C/C+D CER= with placebo but with disease/total with placebo or no intervention

RR risk ratio of the disease in the experimental grp (EER) and the risk in the control grp (CER)

RR= EER/CER If RR is 1 means that the treatment has no effect. If RR is less than 1: effective If RR is greater than 1: mas lumala yung sakit. For cohort study. E.g. in smoking (smoker vs non-smoker). *example: With drug= 100 With disease= 40 EER = 40/100 = .4 With placebo = 100 With disease = 40 CER= 40/100 =.4 RR= EER/CER = 1 (not effective)

Absolute Risk reduction ARR : risk difference is the difference in the event rates for the EER and CER.

ARR= CER-EER *reduction in the risk of the disease. Example: EER = .2 CER=.4 FAKM

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EXPERIMENTAL STUDIES ARR= .4 - .2 = .2 (20% reduction of disease by the drug)

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Relative risk reduction RRR : Relative Risk Reduction - the difference in event rates expressed in a proportional or relative manner, in relation to the control event rate. Often more impressive than the risk difference. The lower the event rate in the control group, the larger the difference between relative risk reduction and risk difference. •

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RRR= CER-EER/CER = ARR/CER RRR= .2/.4 = .5 X 100 RRR = 50%

The relative risk = 0.80 The Absolute risk reduction = 0.10 The numbers needed to treat (NNT) = 10

INTERPRETATION: If the EER is lower than the CER, the ratio is < 1, the treatment favors the disease. If the 95% Confidence Interval of the measure excludes the null value, (1), the relationship is statistically significant. If the numerator (EER) is equal to the denominator (CER) the RR is equal to 1, no relatiohnsip or no effect/ NULL. If EER is higher then CER and the RR is greater than 1, the treament is dangerous to the disease. In cohort study:the exposure is the risk factor of the disease. If the EER is lower than the CER, RR is less than 1 treatment favors the disease or beneficial treatment. Not all beneficial are significant. To know whether it is significantly benefical you look at the 95% confidence interval (lower limit and upper limit). If the upper limit and the lower limit excludes 1 (null value) then it is significantly lower than 1, and is significantly beneficial. If 95% confidence interval excludes 1 or the null value then it is significantly highers than 1. Example: lower limit = .2 upper limit is .8 It excludes 1 so it is significantly lower than 1. Null value/ line of unity  •

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Number needed to treat NNT ; - the number of patients who would have to r eceive the treatment for one of them to benefit. - Calculated as 1 divided by the absolute risk reduction. *no. of people that will have to have the treatment in order to one of them will benefit. *If the number to treat is high, the drug is not good.

1/ARR * The lower the number the better the drug is. *Ideal number Acne needed to treat: 1. Treatment Yes No Example: Oxygenated A study was Water 40 60 made comparing the efficacy of an Placebo 50 50 oxygenated water in treating moderate to severe acne. Results of the study are shown in the table below. The control event rate is The experimental event rate is

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CER = 0.50 EER = 0.40 FAKM

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RISK RATIO / Sample size 95% CONFIDENCE INTERVAL Does not significantly favor treatment because it crossed the line of unity.

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