VEM 5503 Veterinary Epidemiology Sampling and sample size

Transcription

1 VEM 5503 Veterinary Epidemiology Sampling and sample size Jorge A Hernandez Professor UF CVM LACS Deriso Hall Rm 120 Hernandezja@ufl.edu USA Today: celebrating animals US households: 108 million US households with pets: 71 million Cats: 88 million Dogs: 75 million Source: Humane Society of the United States,

2 Pet Overpopulation Estimates Cats and dogs entering shelters each year: 6-8 million C&D euthanized by shelters: 3-4 million C&D adopted from shelters: 3-4 million Dogs reclaimed by owners from shelters: 30% Cats reclaimed by owners: 2-5% Animal shelters in the US: 3,500 Source: Humane Society of the United States, million dairy cows (65,000 dairies) Source: USDA Overview of the US dairy industry,

3 Caseload: equine inpatients. Salmonella positives 5.2 million horses (375,000 farms) Source: USDA census US equine populations,

4 VEM 5503 Veterinary Epidemiology Sampling and sample size Objectives 1 Know different methods of sampling 2 Know type I and type II errors 3 Know different scenarios that require sample size 4 Know how to determine sample size Suggested reading & tools Suggested reading Vet Epi Research (Dohoo et al.): Chapter 2 Vet Epidemiology (Martin et al.): Chapter 2 Tools Episcope Excel SamplePower Other tools (Research Randomizer, Excel, OpenEpi) 4

5 Hierarchy of populations External population Target population Study population (sample) Sampling methods n-probability Probability judgment convenience purposive simple systematic stratified other sampling methods 5

6 Q1. The following is an example of systematic random sampling 1. Every animal in the target pop n has an equal probability of being included 2. A sampling interval is computed as the study pop n divided by the required sample size 3. Prior to sampling, the pop n is divided into mutually exclusive groups based on factors likely to affect the outcome 4. I don t know Every animal in the targ.. 78% A sampling interval is c... 12% Prior to sampling, the p... 4% 6% I don t know Sampling methods Hypothesis testing in observational and experimental studies Cross sectional studies (single sample) Case control studies (two samples) Cohort studies (two samples) Clinical trials (two or more samples) they differ in the amount of information they provide with respect to the population 6

7 Sampling methods cross sectional study Group Disease Disease Exposure: no N Exposure: yes Sampling methods case control study Group Disease Disease Exposure: no N Exposure: yes

8 Sampling methods cohort study Group Disease Disease Shelter: no Shelter: yes N Sampling methods prophylactic clinical trial Group Disease Disease Vaccine: no Vaccine: yes N 8

9 Sampling methods surveillance: provide evidence that hospital facilities are free of Salmonella contamination How many animals do I need? I learned in my stats class that 30 is good number I read one paper in JAVMA and they used 10 dogs Why not 40, more is better; right? Whatever.. 9

10 How many animals do I need? What s the study objective? Common situations requiring sample size calculation Cross sectional (prevalence) studies Case control studies Cohort studies Clinical trials Surveillance: detecting presence of disease 10

11 Importance of sample size Forces specification of outcomes Leads to a stated recruitment goal Encourages development of timetables & budgets Discourages small, inconclusive trials Common mistakes discussion of sample size Unrealistic assumptions Failure to explore sample size for a range of values Failure to account for attrition 11

12 Type I and type II errors What is the P-value? Type I and type II errors.. TEST Decision: Difference? REALITY Difference:

13 Type I and type II errors... TEST Decision: Difference? REALITY Difference: OK Wrong Wrong OK Type I and type II errors. TEST Decision: Difference? REALITY Difference: OK Type I error 5% Wrong Confidence 95% 13

14 Type I and type II errors.. REALITY Difference: TEST Decision: Difference? Power 80% Wrong Type II error 20% OK Type I and type II errors... REALITY Difference: TEST Decision: Difference? Power 80% Type I error Alpha 5% Type II error Beta 20% Confidence 80% 14

15 Q3. Type I error is the probability of 1...declaring there is a difference when in fact there is no difference 2...of failing to declare that there is a difference, when there is no difference 3...declaring there is a difference, when there is a difference 4...failing to declare there is no difference, when there is no difference 5. I don t know..declaring there is a diff... 18%..declaring there is a dif.....of failing to declare tha... 5% 1%..failing to declare there.. 7% 68% I don t know Respiratory disease Respiratory disease Vaccine 36 (16%) 190 (84%) 226 Control 26 (22%) 94 (78%) 120 P = 0.31 JAVMA 1999;215:

16 Respiratory disease Respiratory disease Vaccine 360 (16%) 1900 (84%) 2260 Control 260 (22%) 940 (78%) 1200 P < 0.01 How many animals do I need? Examples... 16

17 How many animals do I need? Prevalence study What s the seroprevalence of canine distemper virus in dogs entering an animal shelter with a history of infectious disease outbreaks? Population size: 400 (admitted over a 2-month period) Expected prevalence: 50% Accepted error: 10% Confidence: 95% Sample size = 78 Human Salmonella infections linked to contaminated dry dog and cat food Case control study. of controls per case: Exposure rate among controls: OR worth detecting: Confidence: 95% Power: 80% Cases = Controls = 17

18 What is the odds ratio? Exposure (dry food) Exposure Disease (Salmonella) Disease (Salmonella) 80 (A) 50 (B) (C) 50 (D) OR = 80 x 50 / 50 x 20 OR = 400 / 100 = 4 OR = 80:20 = 4 OR = 50:50 = 1 OR = 4:1 = 4 Human Salmonella infections linked to contaminated dry dog and cat food Case control study. of controls per case: 3 Exposure rate among controls: 7% OR worth detecting: 5 Confidence: 95% Power: 80% Cases = 31 Controls = 93 18

19 How many animals do I need? Cohort study What s the risk of influenza-like-illness in dogs that go to doggie day care facilities vs dogs that do not? Group 1 (Day care): 60% with severe disease Group 2 (Home): 30% without severe disease RR worth detecting: 2 Alpha: 0.05 Beta: 0.20 N 1 = 40 dogs N 2 = 40 dogs How many animals do I need? Clinical trial What s the efficacy of CIV H3N8 vaccine to decrease severity of clinical disease after cochallenge with CIV and Streptococcus equi in dogs? Group 1 (placebo) (CIV): 90% with severe disease Group 2 (vaccine) (CIV): 30% w/o severe disease Alpha: 0.05 Beta: 0.20 N 1 = 8 dogs N 2 = 8 dogs 19

20 How many animals do I need? Clinical trial What s the efficacy of CIV H3N8 vaccine to decrease severity of clinical disease after cochallenge with CIV and Streptococcus equi in dogs? Group 1 (placebo) (CIV): mean clinical score = 3 Group 2 (vaccine) (CIV): mean clinical score = 1 Standard deviation = 1 Alpha: 0.05 Beta: 0.20 N 1 = 6 dogs N 2 = 6 dogs How many animals do I need? Clinical trial What s the efficacy of CIV H3N8 vaccine to decrease severity of clinical disease after cochallenge with CIV and Streptococcus equi in dogs? Group 1 (placebo) (CIV): mean days virus shedding = 6 days Group 2 (vaccine) (CIV): mean days virus shedding = 4 days Standard deviation = 1, 2 Alpha: 0.05 Beta: 0.20 N 1 = 6 dogs, 18 dogs N 2 = 6 dogs, 18 dogs 20

21 How many animals do I need? Clinical trial What s the efficacy of CIV H3N8 vaccine to decrease severity of clinical disease after cochallenge with CIV and Streptococcus equi in dogs? Group 1 (placebo) (CIV): n = 6 dogs Group 2 (placebo) (S equi); n = 6 dogs Group 3 (placebo) (CIV + S equi); n = 10 dogs Group 4 (vaccine) (CIV + S equi); n = 10 dogs Clinical and Vaccine Immunology 2011;18: The CIV vaccine significantly reduced the clinical scores induced by CIV plus S equi (P< 0.01). Clinical and Vaccine Immunology 2011;18:

22 The mean number of days of virus shedding in groups 1 (CIV) (5.7 days) and 3 ( CIV + S equi) (5.8 days) was significantly higher than for Group 4 (Vaccinate + CIV + S equi) (4 days). The results demonstrate that the CIV vaccine significantly reduced nasal virus shedding in vaccinated dogs. Clinical and Vaccine Immunology 2011;18: How many samples do I need? surveillance: provide evidence that hospital facilities are free of Salmonella contamination Population size: 100 sites Prevalence: 10% Confidence: 95% Sample size: 25 samples (sites) 22

23 Summary objectives 1 Know different methods of sampling 2 Know type I and type II errors 3 Know different scenarios that require sample size 4 Know how to determine sample size Summary: What s the study objective? Prevalence study Case control study Cohort study Clinical trial disease freedom 23

24 Take home message study is perfect; but do it right, be responsible Sample size calculations Exercises using Research Randomizer, Excel and OpenEpi 24

25 How many animals do I need? Prevalence study What s the seroprevalence of canine distemper virus in dogs entering an animal shelter with a history of infectious disease outbreaks? Population size: 400 (admitted over a 2-month period) Expected prevalence: Accepted error: Confidence: Sample size = Cost: tests x $10 = $ How many samples do I need? surveillance: provide evidence that hospital facilities are free of Salmonella contamination Population size: 100 sites Prevalence: Confidence: Sample size: 25

26 Human Salmonella infections linked to contaminated dry dog and cat food Case control study. of controls per case: Exposure rate among controls: OR worth detecting: Confidence: Power: Cases = Controls = How many animals do I need? Cohort study What s the risk of risk of influenza-like-illness in dogs that go to doggie day care facilities vs dogs that do not? Group 1 (Day care): % with ILI Group 2 (Home): % with ILI RR worth detecting: Alpha: Beta: N 1 = N 2 = 26

27 How many animals do I need? Clinical trial What s the efficacy of CIV H3N8 vaccine to decrease severity of clinical disease after cochallenge with CIV and Streptococcus equi in dogs? Group 1 (placebo) (CIV): % with ILI Group 2 (vaccine) (CIV): % with ILI Alpha: Beta: N 1 = N 2 = Question. 1 The following is an example of a stratified random sample A) Every element in the target population has an equal probability of being included B) A sampling interval is computed as the study population divided by the required sample size C) Prior to sampling, the population is divided into mutually exclusive groups based on factors likely to affect the outcome D) ne of the above are correct 27

28 In case-control studies Question. 2 A) Study animals are selected based on exposure (yes, no) to a potential risk factor B) Study animals are selected based on disease status C) Study animals are selected from the target population D) ne of the above are correct Sampling methods case control study Group Disease Disease Exposure: no N Exposure: yes

29 Type I error (alpha, P) Question. 3 A) Is the probability of declaring that there is a difference when in fact there is no difference B) Is the probability of failing to declare that there is a difference when in fact there is no difference C) Is the probability of declaring that there is a difference when in fact there is a difference D) Is the probability of failing to declare there is no difference when in fact there is no difference Type I and type II errors.. REALITY Difference: TEST Decision: Difference? Power 80% Type I error Alpha 5% Type II error Beta 20% Confidence 80% 29

30 Question. 4 To determine the sample size in a case-control study A) We need to specify the expected incidence of disease in an exposed group and a non-exposed group B) We need to specify the expected prevalence of disease in an exposed group and a non-exposed group C) We need to specify the expected exposure among animals classified as negative to a disease of interest D) We need to specify the expected prevalence of disease in the study population VEM 5503 Veterinary Epidemiology Sampling and sample size Q&A 30