Risk Study. Section for Clinical Epidemiology and Biostatistics. Definition

Transcription

1 Risk Study Section for Clinical Epidemiology and Biostatistics What is Risk? Definition The probability of some untoward event The likelihood that people who are exposed to certain factors (risk factors) will subsequently develop a particular disease The proportion of unaffected individuals who, on average, will contact the disease of interest over a specified period of time. 1

2 Definition What is Risk Factor? Characteristics that are associated with an increased risk of becoming diseased Interesting factors which may be associated with unwanted of adverse outcome Risk factors o Inherited: e.g. HLA B27 o Infection: e.g. HIV o Drugs, toxin: e.g. Aspirin overdose o Social, environment: e.g. crowding o Behavior: e.g. smoking, alcohol abuse, driving without seat belts THE FIRST APPEARANCE OF THALIDOMIDE 'Thalidomide Babies' 2

3 Example of Questions Are older age pregnant women at increased risk of autistic child? Dose high trans fat consumption lead to increase risk of breast CA? Dose Soy Milk increase the risk of developing peanut allergy in children? Dose New NSIADs increase risk of GI bleed and CVS than piroxicam? Dose BZP increase risk of fall and femoral fracture in old age patients? Risk Recognition Large risks associated with effects that occur rapidly after exposures are easy to recognize. But most morbidity and mortality is caused by chronic diseases, then the relationships between exposure and disease are far less obvious. Impossible for individual clinicians to develop estimates of risk based on their own experiences with patients (Ethical) 3

4 Risk Recognition Long latency e.g. radiation and CA thyroid Frequent exposure to risk factors e.g. junk food and coronary heart disease Low incidence of disease: it is difficult to draw conclusions about the risk in rare disease. e.g. heavy smoker and lung cancer (incidence < 2/1000) Small risk: e.g. birth control pills and breast cancer. Common disease: the risk factors are already known. It becomes difficult to find a new risk factors. Multiple causes and effects Use of risks Prediction the occurrence of disease Cause eg. marker = the risk factor that is not cause of disease but increases probability of disease. Diagnosis Rule in / Rule out by using risk factors Prevention Risk removal 4

5 Study of Risk Most often used to express the probability that a particular Cohort outcome will occur following a particular exposure is RISK STUDY Case- Control Cross Sectional Others CC EBM STUDIES OF RISK Cohorts Cohort study begins with the exposure to cause or risk and then follow up until the outcome occurs. 5

6 STUDIES OF RISK Case control study : Study runs backwards. Researchers enrolled case (having diseases) and controls (having no disease) and then look back in time to ascertain each person s exposure status. Comparing risks Basic expression of risk is incidence (a number of new cases of disease arising in a defined population during a given period of time) To compare risks, several measures of the association between exposure and disease, called measures of effect, are commonly used. 6

7 Comparing risks (cont) Ie = incidence in exposed persons Io = incidence in non exposed persons P = prevalence of exposure to a risk factor I T = total incidence of disease in a population Comparing risks (cont) 7

8 Example A cohort study of 100 women who had been accidentally exposed to pesticides was followed up overtime and their outcome compared to 100 women who had not been exposed to pesticides. 30 women who had been exposed suffered miscarriages. Compared to10 women who had not been exposed. What is the incidence of miscarriage attributable to pesticide exposure? How many times more likely are exposed persons to become miscarriage, relative to non exposed persons? What is the incidence of miscarriage in a population, associated with the occurrence of a pesticide exposure? What fraction of miscarriage in a population is attributable to exposure to pesticide? To calculate & interpret the OR results? Answers 8

9 Answers Answers 9

10 Answers Answers OR = Odds that diseased person has been exposed Odds that non diseased person has been exposed = {(a/a+b)/ (b/a+b)} / {(c/c+d)/(d/c+d)} = (a/b) / (c/d) = ad/bc = (30 x 90) / (70 x 10) = 2700/700 = 3 (95 % CI = ) is not significant. 10

11 RISK AND PREVENTION If the exposure is prevention, so that Ie (incidence among exposed) is less than Io (incidence among unexposed), the attributable risk is meaningless. The prevention fraction (PF) can be defined. PF = Io Ie Io CAUSE? Does it really cause a disease? Is this exposure really causing disease or ill health in the population at risk? Marker is a risk factor that does not cause a disease. How can we tell a cause of a disease? 11

12 Criteria for judgment of causal Temporal sequence Did exposure precede outcome? Strength of association How strong is the effect, measured as relative risk or odds ratio? Consistency of association Has effect been seen by others? Biological gradient (dose response relationship) Does increased exposure result in more of the outcome? Specificity of association Does exposure lead only to outcome? Biological plausibility Does the association make sense? Coherence with existing knowledge Is the association consistent with available evidence? Experimental evidence Has a randomized controlled trial been done? Analogy Is the association similar to others? From Hill AB. Principles of medical statistics EBM : Critical Appraisal Are the results valid? In a cohort study, aside from the exposure of interest did the exposed and control groups start and finish with the same risk for the outcome? Were patients similar for prognostic factors that are known to be associated with the outcome (or did statistical adjustment level the playing field)? Were the circumstances and methods for detecting the outcome similar? Was the follow up sufficiently complete? In a case control study, did the case and control group have the same risk (chance) for being exposed in the past? Were case and controls similar with respect to the indication or circumstances that would lead to exposure? Were the circumstances and methods for determining exposure similar for case and controls? Users Guides for an Article About Harm Gordon Guyatt 12

13 EBM : Critical Appraisal What are the results? How strong in the association between exposure and out come? How precise is the estimated of the risk? How can I apply the results to patient care? Were the study patients similar to the patient in my practice? Was follow up sufficiently complete? Is the exposure similar to what might occur in my patient? What is the magnitude of the risk? Are there any benefits that are known to be associated with exposure? Users Guides for an Article About Harm Gordon Guyatt Clinical Question in OPD DM patient(65 years old) in OPD, was recently lab of HbA1c =9 many times after had symptom of polyuria and high blood sugar. The doctor prescribe Pioglitazone oral to patient after failed treatment with Glipizide & metformin and clinical well and controlled DM condition with FBS 120 mg/dl and HbA1c =5 Patient was read Newspapers and found association of CA bladder and New drug(pioglitazone that he treated and concerned the ask you about this? 13

14 Transform Clinical Question to PICO P : DM Patient I : Pioglitazone (Thiazolidinedione group) C : Other anti diabetic drugs (Others than thiazolidinedione group) O : CA bladder event Searching PubMed SCOPUS EMBASE 14

15 Search strategy ("Diabetes Mellitus"[Mesh] AND ("Thiazolidinediones"[Mesh] OR "pioglitazone"[supplementary Concept])) AND "Urinary Bladder Neoplasms"[Mesh] 15

16 Why select? Recent update in 5 years Large cohort of UK Good Methodologic : Nest case control study based on well designed cohort study BMJ High impact factor (impact factor of 17.4 (June 2015) Relevant to our PICO 16

17 Are the results valid? In a case control study, did the case and control group have the same risk (chance) for being exposed in the past? Were case and controls similar with respect to the indication or circumstances that would lead to exposure? Yes, UK general practice research database It contains the complete primary care medical record of more than 10 million people enrolled in more than 600 general practices. The geographical distribution of the practices has been shown to be representative of the UK population Cohort DB: Patient enrolled before had CA bladder, Time of enroll was tie of any types anti diabetic was started. Patient are equally chance to receive any type anti diabetic drug by primary doctor. 17

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19 Are the results valid? Were the circumstances and methods for determining exposure similar for case and controls? Yes, Carefully diagnosis was done by the Read classification of UK. Anti diabetic Prescriptions was prescribed and recorded base on prescription Pricing Authority Dictionary. Patients were classified into 5 groups to compare between Case : Control 1.Exclusive categories for use of thiazolidinediones: 2.Exclusive ever use of pioglitazone 3.Exclusive ever use of rosiglitazone 4.Ever use of both pioglitazone and rosiglitazone (mainly switchers from one drug to the other), 5.Control group: never use of any thiazolidinedione, served as the reference category in the analyses Anti Diabetic Drugs vs. CA Bladder 19

20 RANGE OF VALIDITY Not valid 25% 50% 75% Valid Case and controls similar with respect to the indication or circumstances that would lead to exposure Circumstances and methods for determining exposure similar for case and controls What are the results? How strong in the association between exposure and out come? The primary analyses were restricted to 376 cases, matched to 6699 controls (1: 20), with at least one year of follow up between cohort entry and index date to account for latency. Exclusive ever use of pioglitazone group was associated with an 83% increased rate of bladder cancer (adjusted rate ratio 1.83, 95% CI 1.10 to 3.05). * This corresponded to an absolute adjusted rate difference of 74 per 100, 000 person years (95% CI 9 to 140) * This effect was not observed for exclusive ever use of rosiglitazone (adjusted rate ratio 1.14, 95% CI 0.78 to 1.68), the other thiazolidinedione available in the United Kingdom during the study period. 20

21 Thiazolidinediones and risk of bladder cancer among cases of bladder cancer and matched controls* What are the results? Researchers compared exclusive ever users of pioglitazone with exclusive ever users of rosiglitazone. The adjusted rate ratio was numerically increased but did not reach statistical significance (adjusted rate ratio 1.60, 95% CI 0.88 to 2.90) Found the evidence of a dose response relation between pioglitazone use and the rate of bladder cancer with the highest rate observed in users of more than 24 months (adjusted rate ratio 1.99, 95% CI 1.14 to 3.45) Statistically significant association was observed in patients who received more than 28,000 mg (2.54, 95 %CI 1.05 to 6.14) 21

22 Pioglitazone cumulative duration of use and cumulative dosage and risk of bladder cancer among cases of bladder cancer and matched controls What are the results? expose non expose NNH is ve show the control condition is more likely to harm than the treatment condition How precise is the estimated of the risk? Yes, Narrow ranges of 95 %CI 22

23 RANGE OF RESULTS Poor 25% 50% 75% Good Strong in the association between exposure and out come Good Precision How can I apply the results to patient care? Were the study patients similar to the patient in my practice? Yes, but differences of ethnics (should be compare incidence of CA bladder between UK and Thai and ware for difference life styles, Socioeconomic environment through genetic differences) Local made also are available in Thailand. Was follow up sufficiently complete? Yes, but not clearly mention only declare 1 cases of control to exposed to Pioglitazone) Is the exposure similar to what might occur in my patient? Yes What is the magnitude of the risk? Pioglitazone group was associated with an 83% increased rate of bladder cancer (adjusted rate ratio 1.83, 95% CI 1.10 to 3.05) and Significant in dose response relationship. Are there any benefits that are known to be associated with exposure? Yes, for awareness and regulation of use. 23

24 Should I Stop exposure or alternating exposure to keep high benefit and low risks? Yes, We can stop this exposure by use other anti diabetics drugs. And wait for further studies or meta analysis to answers this question. Thank You ceb rama.org 24