Design II: Cohort Studies. Cross-sectional Surveys. Laufey Tryggvadóttir Icelandic Cancer Registry Faculty of Medicine, UI

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1 Design II: Cohort Studies Cross-sectional Surveys Laufey Tryggvadóttir Icelandic Cancer Registry Faculty of Medicine, UI Nordic Summer School in Cancer Epidemiology August 17 th, 2017

2 Studying the Causes of Disease Exposure > outcome Laboratory research Epidemiological research

3 Epidemiological Design Intervention Studies Observational Studies

4 Observational studies Cohort studies Exposure -----> Outcome Case control studies Exposure <----- Outcome

5 Cohort Studies marching towards the outcome Grimes DA, Schultz KF. Lancet 2002;359:341-45

6 COHORT Definition by Last, JM. A Dictionary of Epidemiology Any designated group of individuals who are followed or traced over a period of time From Latin: cohors, warriors, the tenth part of a legion

7 Birth cohorts and: tuberculosis death rates From Last JM: A Dictionary of Epidemiology

8 Cohort Studies follow-up longitudinal - prospective - studies Resemble intervention studies in that information on exposure is registered before onset of disease > a prospective relationship between the recording of information on exposure and the outcome Incidence is compared between two groups: exposed and non-exposed > Relative risk can be calculated directly

9 Lexis Diagram (from NOCCA Study) Follow-up of Census Population from 1981

10 Example lung cancer epidemic Lung cancer deaths in England and Wales : 1.1 per : 10.6 per

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12 Example lung cancer epidemic Doll R and Hill AB. Mortality in relation to smoking: Ten year s observations of British doctors. BMJ 1964;1: Started 1951, British doctors (without cancer) questions about smoking and exposure to environmental smoke. First follow-up after 10 years Daily Mortality per 1000 smoking (lung cancer) None cig cig cig 2.27

13 Example lung cancer epidemic Doll R and Hill AB. Mortality in relation to smoking: Ten year s observations of British doctors. BMJ 1964;1: Started 1951, British doctors (without cancer) questions about smoking and exposure to environmental smoke male doctors responded. First follow-up after 10 years Daily Mortality per 1000 Relative Risk smoking (lung cancer) (RR) None cig cig cig

14 Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to alcohol consumption: a prospective study among male British doctors. Int J Epidemiol Feb;34(1):

15 Example - NOCCA Cohort Study Pukkala E et al. Occupation and cancer follow-up of 15 million people in five Nordic countries. Acta Oncologica 2009;48: million individuals years at census (1960, 1970, 1980(1), 1990) - Record linkage between census data and Cancer Registries - Follow-up for cancer until death, emigration or end of study (e.g. 2005) -> 2.8 million cancers -> Examples of results: SIR All cancer in Waiters (male) 1.48 ( ) All cancer in Farmers (male) 0.83 ( )

16 NOCCA Study Population, follow-up

17 Nordic Occupational Cancer (NOCCA) Study Group

18 Some important Cohort Studies Framingham Heart Study 5200 residents of Framingham, USA, started 1950 British Physicians Study doctors (mainly males), started 1951 Nurses Health Study female nurses USA, started 1976 European Prospective Investigation Into Cancer and Nutrition EPIC > subjects in 10 countries, started 1992/1998

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20 2017

21 Perez-Cornago A et al. Fruit and vegetable intake and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer Perez-Cornago A et al. Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study. BMC Med 2017 Agudo A et al. Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Carcinogenesis Sala N et al. Prostate stem-cell antigen gene is associated with diffuse and intestinal gastric cancer in Caucasians: results from the EPIC- EURGAST study. Int J Cancer Bingham SA et al. Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study. Lancet Norat T et al. Meat, fish, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. J Natl Cancer Inst. 2005

22 Sources of Study Population 1. A general population cohort (e.g. geographically defined or a socio-professional group) Examples: The Framingham Study, Nordic Occupational Cancer Study (NOCCA) 2. A highly exposed group (if exposure is rare) Example: the Life Span Study - atomic bomb survivors

23 Framingham study Hypothesis: Various measurable factors affect the risk of heart disease Exposure: Blood pressure, smoking, cholesterol etc. in serum, diet, physical exercise Cohort: Residents of Framingham Massachusets aged years (5000 individuals) Outcome: Heart disease, atherosclerosis, diabetes etc. Follow up: >

24 The Life Span Study (Shimizu et al., 1990) Hypothesis: High levels of ionizing radiation cause various cancers Exposure: Radiation from atomic bomb Hiroshima and Nagasaki Cohort: individuals resident in H and N in 1950 Outcome: Death from cancer Follow up: Started 1950, still ongoing

25 Radiat Res Dec;160(6): Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, Land CE, Tokunaga M, Koyama K, Soda M, Preston DL, Nishimori I, Tokuoka S. The increased risk of breast cancer was highest if exposure occurred before age 20 years

26 Comparison Group A group of unexposed individuals Must otherwise be very similar to the exposed group Internal comparison group Those unexposed in the cohort Examples: Framingham study British Physicians Nurses Health Study

27 Nurses Health Study (Romieu et al., 1989) Hypothesis (one of many): Oral contraceptives are a causal factor in breast cancer Exposure (one of many): Oral contraceptive use Cohort: US female registered nurses, aged years Outcome: Incidence of breast cancer Follow up: 1976 to 1986 (1800 cases) -> the study is still ongoing over 400 publications

28 Nurses Health Study (Romieu et al., 1989) Compared with nonusers of oral contraceptives, the multivariate relative risks were 1.07 (95% confidence interval, ) for all users 1.06 (95% confidence interval, ) for past users 1.53 (95% confidence interval, ) for current users--women who used oral contraceptives up to 2 years before diagnosis of breast cancer

29 Nurses Health Study (Examples of studies) Osganian SK et al. Am J Clin Nutr Dietary carotenoids and risk of coronary artery disease (CAD) in women - In 1984: Semiquantitative food frequency questionnaire female nurses - 12 years of follow-up ( person-years) incident cases - adjustment for age, smoking etc. - RR of CAD - beta-carotene (highest v.s. lowest quintile of intake): 0.74 (95% CI: )

30 Nurses Health Study (Examples of studies) Feskanich D, Willett WC, Colditz GA, Am J Clin Nutr Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women : Dietary intake and nutritional supplement assessed postmenopausal women - 18 years of follow-up incident hip fractures - adjustment for other dietary and non-dietary factors - Adequate vitamin D intake associated with lower risk of osteoporotic hip fractures in postmenopausal women. Neither milk nor a high-calcium diet reduced risk.

31 Comparison Group (continued) External comparison group For exposed cohorts (e.g. asbestos workers) A special selected group (e.g. other workers) General population in the same area + No special follow-up needed - Information on exposure may not exist - Exposure must be rare - Groups may differ (diet, smoking etc.) Sometimes more than one comparison group

32 Mortality of rubber workers (McMichael et al., 1974) Hypothesis: Working in tyre-manufacturing plants increases mortality Exposure: Working in a tyre-manufacturing plant Cohort: 6678 male rubber workers Outcome: All-cause mortality Follow up: From 1964 to 1972

33 Mortality of rubber workers (continued) Age-specific mortality rates (per pyrs) Age gr. Rubber cohort Steel cohort Ohio state 1972 USA

34 HEALTHY WORKER EFFECT may mask harmful effects of the exposure

35 McMichael AJ. J Occup Med Mar;18(3): Standardized mortality ratios and the "healthy worker effect": Scratching beneath the surface. Comparing to the general population, SMR for an occupational population will underestimate the mortality experience since it comprises individuals necessarily healthy enough to be employable - and whose mortality risk is therefore initially lower than the general population average The "healthy worker effect" varies according to age, race, work-status groups, causes of death, and elapsed-time periods of observation

36 Exposure Important to have exposure information on: - type - dose - age at first exposure - duration - pattern (intermittent v.s. constant) - changes in exposure levels (i.e. smoking)

37 Timing of exposure assessment Prospective Cohort Studies Historical (retrospective) Cohort Studies

38 A historical cohort study - a classic Case RA, Hosker ME, McDonald DB, Pearson JT. Tumours of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. I. The role of aniline, benzidine, alpha-naphthylamine, and beta-naphthylamine Br J Ind Med Apr;11(2): Exposure: Dyestuff intermediates (e.g. aniline, betanaptylamine) Cohort: Employees in the chemical industry in UK at least for 6 months, known to have contact with dyestuffs Outcome: Bladder cancer incidence - from hospital and firm records plus death certificates Follow up: Starting 1920, followed until 1951

39 Historical (retrospective) Cohort Studies Exposure data often limited proxy variables used instead But non-differential misclassification of exposure likely Information on potential confounders limited Biological specimen banks an excellent source of exposure for this type of studies

40 A historical cohort study from the Nordic Cancer Registries - ANCR Olsen J et al. Lifelong Cancer Incidence in Patients Treated for Childhood Cancer in the Nordic Countries. JNCI ,697 children and adolescents 0-19 years diagnosed in Follow-up for second primary cancer until death, emigration or end of study (December 31st 2005) -> 1180 new cancers in 1088 individuals -> Standardized incidence ratio (SIR) of 3.3 (95% CI, 3.1 to 3.5)

41 Olsen J et al. Lifelong Cancer Incidence in Patients Treated for Childhood Cancer in the Nordic Countries. JNCI 2009;101:

42 Olsen J et al. Lifelong Cancer Incidence in Patients Treated for Childhood Cancer in the Nordic Countries. SIR=1.5 JNCI 2009;101: One extra case per 1000 person years in early life SIR=2.3 Six extra cases per 1000 person years at ages SIR=6.7

43 Adult Life after Childhood Cancer in Scandinavia (ALiCCS) de Fine Licht S et al. Hospital contacts for endocrine disorders in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): a population-based cohort study. Lancet 2014;383(9933): Lifetime risk of endocrine disorders Cancer registries: Denmark, Finland, Iceland, Norway, Sweden 31,723 survivors of childhood cancer Record linkage with national hospital registries Observed numbers of endocrine disorders Expected numbers from a population comparison cohort

44 >60 Age (years)

45 ALiCCS endocrine disorders - continued An overall 4 8-times increase in risk for a hospital contact for any endocrine disorder -> importance of minimizing damaging treatment intensifying secondary prevention targeting of survivor follow-up throughout life

46 Comment in Lancet 2014;383(9933): Oeffinger KC & Sklar CA. Childhood cancer, endocrine disorders, and cohort studies This study makes several substantial and novel contributions to our understanding of the long-term and late effects of curative treatment for childhood cancer Six large cohort studies worldwide since 1994: ALiCCS is the largest of the six - loss to follow-up only <1% (20-40% in others) - long term and late effects attained by record linkage (self reported in other studies) - matched population based comparison group (other studies had none except one used siblings)

47 Measurement of Potential Confounding Variables Not random allocation to exposure categories -> Essential to collect from the start data on potential confounders Sometimes matching is used to ensure a similar distribution with respect to confounders in the exposed and unexposed group More commonly: Statistical adjustment

48 Outcome Cohort studies: Multiple outcomes Surveillance systems: Cancer registries, death certificates Otherwise - questionnaires Same procedure for exposed and unexposed if not: Measurement bias -> blinding Disease-free at entry > exclude the first 2-3 years

49 Follow-up Criteria for entry must be clear Periodic contacts with study subjects - expensive Criteria for exit must be well defined If incomplete follow-up, selection bias may be introduced

50 Analysis Incidence can be calculated for both groups Calculate risk if follow-up time is uniform Calculate rates if person-time at risk differs between subjects Contribution of an individual to different categories is possible:

51 Nurses Health Study Hypothesis: Oral contraceptives are a causal factor in breast cancer Exposure: Oral contraceptive use Cohort: US female registered nurses, aged years Outcome: Incidence of breast cancer Follow up: Started 1976, still ongoing

52 Nurses Health Study Initial questionnaire Repeated 1978, 80, 82 and Analysis done 1986 Individual contribution to person-time according to exposure status using the updated information Follow-up truncated at time of breast cancer diagnosis Outcome allocated to exposure categories according to status at diagnosis

53 Nurses Health Study Follow-up July 1st 1976 to July 1st 1986 Example for a woman using OCs Jan Dec 1984: - July Dec 1977: 1.5 y non-user - Jan Dec 1984: 7.0 y curr user - Jan Jul 1986: 1.5 y past user Diagnosis (dx) cancer Dec > thus only 5 y of current use before dx Allocated to current user category at dx

54 Nurses Health Study Oral contraceptive use Ever (current or past use) Never Total Cases Personyears at risk Rate per pyrs RR = 1.16

55 Analysis (continued) Presence of an exposure-response (dose-response) relationship strengthens the conclusions The shape of the exposure-response relationship curve does not have to be linear If confounding restrict the analysis or adjust, e.g. adjust for smoking when studying effects of alcohol use SMR

56 Male asbestos workers: Analysis (continued) SMR (standardized mortality ratio) Observed: 24 lung cancer deaths among workers Expected: 7 lung cancer deaths, based on the age-specific lung cancer mortality rates of the population O / E = 24 / 7 = 3.4 (or 340%)

57 Bohemian Uranium Miners Cohort compared with the general population of former Czechoslovakia

58 WLM = Working Level Months

59 Nested Case-Control Studies...within a Cohort Combine advantages of both types of studies: Prospective relationship between exposure and outcome (no question of causal direction) Information on exposure systematically collected (same as historical cohort studies ) share the advantage of low cost and time duration Often the preferred design in biobank studies and nutritional cohort studies

60 Mueller et al. Hodgkin s disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med Mar 16;320(11): Hypothesis: EBV precedes the development of Hodgkin s disease (EBV is a causal factor) Exposure: Elevated levels of IgG and IgA antibodies against viral capsid antigen of EBV Cohort: persons having contributed to serum banks in USA, Norway and Sweden 43 patients were identified from the cohort and 96 controls Outcome: Hodgkin s disease Follow up: On the average 50.5 months

61 Hodgkin s disease and Epstein-Barr virus - continued For elevated levels of IgG and IgA antibodies HR = 2.6 ( ) and 3.7 ( ), respectively Associations stronger in samples obtained >= 3 years before dx than closer to diagnosis ->development of Hodgkin's disease may in some patients be preceded by enhanced activation of Epstein-Barr virus

62 Nordic Biological Specimen Banks working group on Cancer Causes and Control: Nordic co-operation: > 30 studies since 1995 Large cohorts, e.g. Maternity cohorts in Finland and Iceland, Janus bank in Norway and Umea cohort Exposure: seropositivity for HPV infection or other virus infections Outcomes: - cervical cancer - esophageal squamous cell carcinoma - non-cervical anogenital cancers - prostate cancer Other exposures: Chlamydia trachomatis, smoking (cotinine)

63 Nordic Biological Specimen Banks working group on Cancer Causes and Control One example: Kapeu AS et al. Is smoking an independent risk factor for invasive cervical cancer? A nested case-control study within Nordic biobanks. Am J Epidemiol 2009 Results confirm that smoking is an independent risk factor for cervical cancer in women infected with oncogenic HPVs -> importance of cervical cancer prevention among women exposed to tobacco smoke.

64 Example of a recent cohort study using the unique Nordic Health Databanks linked on PIN numbers Fang F, Fall K, Mittleman MA, Sparén P, Ye W, Adami HO, Valdimarsdóttir U. Suicide and cardiovascular death after a cancer diagnosis. N Engl J Med

65 A historical cohort study - 6,073,240 Swedes in Using PIN numbers: Census data linked with nationwide Cancer-, Causes of Death-, and Migration - registers. Risk of suicide - comparing with cancer-free persons First week after diagnosis adjusted RR =12.6 (8.6 to 17.8) First year after DX RR = 3.1 (2.7 to 3.5) Risk of cardiovascular death First week after diagnosis adjusted RR = 5.6 (5.2 to 5.9) First 4 weeks adjusted RR = 3.3 (3.1 to 3.4) Increased risk was particularly prominent for cancers with a poor prognosis.

66 Cohort Studies Key Issues + Exposure is the starting point -> unbiased information and causal direction clear + Rare exposures can be studied + Multiple outcomes can be studied + Incidence can be measured Expensive - Exposure classification can change with time - Information bias for outcome is possible - Selection bias due to loss to follow-up or due to healthy worker effect is possible

67 Cohort Studies Key Issues (continued) For reducing costs: Use pre-existing records (historical studies) Use available survey systems Use national rates for comparison Conduct a nested case-control study

68 S ds

69 Design II: Cross-sectional Surveys

70 World Fertility Surveys (United Nations, 1987) Aim: To compare human reproductive behaviour in 40 developing and 20 developed countries

71 Mean duration of breast feeding (months) by country and years of schooling Country Zero Egypt Colombia Bangladesh n.a. n.a.

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73 Crude Birth Rate Data from Civil registration systems, Sample surveys, Censuses Number of live births occurring in the household in 12 months preceding survey (census), or date of birth of the last child born alive in the household Surveys and Censuses provide less reliable estimates than civil registration - rely on recall Censuses - every 10 years Surveys every three to five years in developing countries

74 Number of births in China 1970, 1985, 1995, 2005, 2011 Number of Crude birth Source type Survey name births rate / ,0 Survey China 1982 National One-per-Thousand- Population Sample Survey on Fertility ,8 Registration ,0 Survey ,4 Survey ,9 Survey China 1995 One-percent Sample Survey China 2005 One-percent Sample Survey China 2011 National Sample Survey on Population Changes

75 The main surveys utilized: Demographic and Health Surveys (DHS) Reproductive Health Surveys (RHS World Fertility Survey (WFS) Multiple Indicator Cluster Surveys (MICS) Contraceptive Prevalence Surveys (CPS) other nationally sponsored surveys

76 Lahti-Koski M et al. Eur J Cardiovasc Prev Rehabil 2007 Fifteen-year changes in body mass index and waist circumference in Finnish adults National Public Health Institute, Department of Health Promotion and Chronic Disease Prevention, Helsinki, Finland

77 Design Four cross-sectional population surveys in Finland Methods 9025 men / 9950 women, aged years Weight, height, and waist circumferences measured using a standardized protocol, responses to a questionnaire Results Mean waist circumf. increase: 2.7 cm in men, 4.3 cm in women Increase in all educational groups Highest values among subjects with lowest education Conclusions One in five Finnish adults defined as obese -> an even larger group at risk of obesity-related metabolic disorders because of abdominal obesity, particularly among low-educated individuals

78 Laskowska L. Ann Agric Environ Med Availability of health services vs. health condition of residents of rural areas in Poland - Analysis performed on the basis of EHIS 2009 RESULTS: Significant differences in the distribution of medical services utilization with regard to income, were found only in the case of hospital services. People with low income stay in hospital more often. European Health Interview Survey (EHIS) Public health policies need data on health status, health care use and health determinants on a regular basis from population surveys The first wave of European Health Interview Survey (EHIS) was implemented in 17 Member States between 2006 and 2009

79 Use of Cross-sectional Surveys Determine magnitude of a problem Useful for planning prevention strategies Help to establish health priorities Background information for etiological studies

80 Target population and study sample Data collection Analysis Interpretation

81 Target Population and Study Sample Aims well defined before initiation of the study Target population / Source population Is the sample representative? (sampling frame e.g. national registry) Sampling unit an individual, a household Study participants -> Can results be extrapolated? A random sample if possible

82 Helicobacter pylori infection (Malaty et al., 1996) Aim: To determine prevalence of Helicobacter infection Target population: Population of Seoul, Korea Source population: Health care attendants Sample: All asymptomatic healthy adults and children visiting one health screening centre for routine examination (convenience sampling) N.B. SELECTION BIAS lower socioeconomic classes underrepresented

83 Scand J Public Health Perceptions of potential donors in the Swedish public towards information and consent procedures in relation to use of human tissue samples in biobanks: a population-based study. Kettis-Lindblad A, Ring L, Viberth E, Hansson MG. Department of Pharmacy, Uppsala, Sweden AIMS: To assess the Swedish public's preferences for information and consent procedures when being asked for permission to use previously collected tissue samples for new research studies METHODS: Cross-sectional study - postal questionnaires - random sample of the Swedish general public (n = 6,000) October 2002-February % response rate CONCLUSIONS: The majority of the Swedish general public prefer general consent, and are willing to delegate some decisions to the research ethics committee.

84 The Journal of Infectious Diseases 2007 The burden of genital warts. A study of nearly 70,000 women from the general female population in four Nordic countries Susanne Krüger Kjær et al. 69,147 women (18 45 years of age) randomly chosen from the general population in Denmark, Iceland, Norway, and Sweden Population-based cross-sectional study Information on clinically diagnosed genital warts and lifestyle habits collected using a questionnaire

85 The Icelandic sample Age-stratified sample from the National Registry Using the PIN Ages (31. October 2004) Birth years women (48.5% of all women in target ages) 452 women ineligible (living abroad) women responded 54.6%

86 Information collected Sociodemographic variables Smoking history Alcohol intake Reproductive history Contraceptive use Sexual habits Ever having had a clinical diagnosis of genital warts Genital warts diagnosed during the previous 12 months Age at first diagnosis of genital warts Previous episodes of other STD

87 Table 1. Mode of response according to country Included by means of Paper-based questionnaire Web-based questionnaire Telephone interview Denmark 76% 9% 15% Iceland 59% 38% 3% Norway 78% 12% 10% Sweden 53% 36% 11%

88 Selected characteristics with regard to sexual habits and genital warts Denmark Iceland Norway Sweden History of clinically diagnosed genital warts (%) Lifetime number of sexual partners (mean (range)) 8.4 (0-500) 8.8 (0-100) 7.4 (0-100) 8.6 (0-450) Age at first diagnosis of genital warts (mean (range)) 21.9 (6-45) 21.3 (14-43) 22.7 (3-45) 21.9 (14-44) Genital warts in the last 12 months (%)

89 Number of partners and % diagnosed with genital warts Number of Ísland sexual partners % 0 (n=240) 1,3 1 (n=1.667) 2,1 2-4 (n=3.430) 6,8 5-9 (n=4.097) 11, (n=2.577) 17,5 15 (n=752) 22,8

90 4 Nordic countries: Correlates of ever receiving a clinical diagnosis of genital warts, multivariate analysis Number % with warts OR OR 95% CI (age adjusted) (adj. for all variables) Age at first intercourse > 20 or never <= Number of sexual partners >

91 4 Nordic countries: Correlates of ever receiving a clinical diagnosis of genital warts, multivariate analysis Number % with warts OR OR 95% CI (age adjusted) (adj. for all variables) Age at first intercourse > 20 or never <= Number of sexual partners >

92 Fig. 2a Prevalence (%) Denmark Iceland Norw ay Sw eden Prevalence of selfreported clinically dx genital warts by birth cohort and country Birth cohort Fig. 2b 12 Mean no. of partners Denmark Iceland Norw ay Sw eden < 1963 Birth cohort Mean lifetime no. of sex. partners by birth cohort and country

93 Estimated cumulative incidence of self-reported clinically diagnosed genital warts Iceland 0,2 0,16 0,12 0,08 0, Age

94 Estimated cumulative incidence of self-reported clinically diagnosed genital warts by country and birth cohort Denmark Sweden 0,2 0,2 0,16 0,16 0,12 0,12 0,08 0,08 0,04 0, Age Age Iceland Norw ay 0,2 0,2 0,16 0,16 0,12 0,12 0,08 0,08 0,04 0, Age Age

95 Jensen KE, Munk C, Sparen P, Tryggvadóttir L, Liaw K-L, Dasbach E, Nygard M, Kjær SK. Women's sexual behavior. Population-based study among 65,000 women from four Nordic countries before introduction of human papillomavirus vaccination. Acta Obstet Gynecol Scand. 2011

96 Variables associated with >= 10 lifetime sexual partners Country: Iceland OR=1.34 Sweden OR=1.31 Age at first intercourse: <=14 years OR=6.89 STD: OR= 3.28 Smoking OR = 2 Alcohol use ->

97 Variables associated with >= 10 lifetime sexual partners (continued) >=10 sexual partners Alcohol use Number % OR Never < one unit per week units per week units per week >= 15 units per week

98 Was the Icelandic sample representative with respect to sexual behaviour? Response rate was 54.6%

99 Attendance to Nationwide Screening for Cervical Cancer Respondents compared with non-respondents - age years at survey, checked in May Last attendance to screening before survey Years Years Before Ever attended Respondents 15,025 64% 18% 4% 12,922 (86%) Non-resp. 12,975 46% 19% 8 % 9,548 (73%) Total 28,000 22,470 (80%)

100 Results from PAP smears at last attendance to screening Respondents compared with non-respondents - age years at survey, checked in May Non-respondents Respondents number (%) number (%) Total (100%) (100%) Normal smear (82,2%) (81.2%)

101 Why a stratified sample? Stratified random sampling: E.g. a random sample within age groups Ensures adequate sample size in each stratum Allows for independent results for different strata.

102 Response Rate Report the number in the initial sample as well as the number of respondents Selection bias? obtain information on non-respondents small random sample from non-respondents Use any information available (age, sex etc.) Important to make efforts to include as many as possible of the initial sample (visit households at different times of the day etc.) A

103 Questionnaires Self administered Personal interview Telephone interview Data Collection Sometimes blood samples and diagnostic tests Important! Do a pilot study before you start

104 Analysis A random sample of 5891 women 201 had breast cysts overall prevalence was 201 / 5891 = 3.4% Breast cysts Lifetime use of oral contraceptives Ever used Never used Total Yes 124 (3.8%) 77 (2.9%) 201 No Total

105 Easy and economical Interpretation Multiple exposures and multiple outcomes Usually not for studying causal relationships Based on prevalent cases Time sequence often uncertain -> Except for exposures that do not change with time Not for studying rare conditions thus in cancer epidemiology limited to factors associated with prevalence of precursor lesions

106