Inferring… What? Stefano Petti Dept. Public Health & Infectious Diseases Sapienza University Rome Italy INFERENCE comes from the Latin word composed by ferre = bring & in = in and means inferre bring in Thus, inference refers to the process of drawing conclusions relative to the underlying study population starting from a sample which is subject to observational errors or sampling variation INFERENCE A sinonymous of INFERENCE is INDUCTION which comes from another Latin word inducere and means, once again, bring in When we make inference/induction we BRING something IN the studypopulation INFERENCE/INDUCTION VS. DEDUCTION INFERENCE is radically different from DEDUCTION Another Latin word composed by ducere + de which means bring out / extract When we make deduction we bring something out (from a sample), when we make inference we bring something in (the study-population) How do inference/induction and deduction function? Which is the process of knowledge (science)? Two completely distinct parts 1-our deduction from our sample 2-our inference in the underlying study-population Example (part 1 - DEDUCTION) Gurbuz O, et al. Community Dent Health 2010;27:151-7 Prevalence of edentulousness in adult Turkish hospitalized chronic psychiatric patients Sample, 491 subjects, mean age 52.3 (sd, 12.3) Number of edentulous patients, 89 We DEDUCE that 18.1% of the sampled subjects were edentulous Example (part 2 – INFERENCE/INDUCTION) Can we say that 18.1% of ALL adult Turkish institutionalized psychiatric patients (the underlying study population) are edentulous? Sample prevalence IS NOT the population prevalence We need to calculate the 95% confidence interval 14.7% to 21.5% INFERENCE = We can say that a proportion between 14.7% and 21.5% of ALL adult Turkish institutionalized psychiatric patients are edentulous How do inference/induction and deduction function? Which is the process of knowledge (science)? Two completely distinct parts 1-we bring something out from our sample (deduction) 2-we bring something in the study population (inference/induction) AFTER AN ADAPTATION PROCESS!!! Which are the causes of wrong inference? wrong deductions good deductions lead to wrong inference mined by wrong inference biased study wrong deductions due to incomplete deductions Which are the causes of wrong inference? WRONG INFERENCE MAY ARISE FROM STUDY DESIGN DEDUCTION INFERENCE EXAMPLE-1 BIASED STUDY Gomez I, et al. Eur J Oral Sci 2009;117:541-6 Is diagnostic delay related to advanced-stage oral cancer? A meta-analysis OR advanced-stage cancer due to diagnostic delay = 1.32 [1.07 to 1.62] Authors’ inference The probability that delayed diagnosis patients present an advanced stage tumour at diagnosis is approximately 30% higher than for non-delayed diagnosis patients There were several errors in the meta-analytic methods, the Authors used the fixed-effect method, which does not apply in MA of observational studies (confirmed by high between-study heterogeneity) and did not study the effect of correction for publication bias EXAMPLE-1 BIASED STUDY Petti S. Eur J Oral Sci 2010;118:210-1 Diagnostic delay is not associated with advanced-stage oro-pharyngeal cancer Meta-analytic method OR 95CI Fixed-effect 1.32 1.07 to 1.62 Random-effect 1.15 0.89 to 1.48 Fixed-effect adjusted for publication bias 1.08 0.87 to 1.34 Good inference: data do not allow to infer that patients with diagnostic delay are at higher risk for oro-pharyngeal cancer at an advanced stage EXAMPLE-1 BIASED STUDY Gomez I, et al. Eur J Oral Sci 2010;118:212 Diagnostic delay may be associated with advanced-stage oro-pharyngeal cancer This is a good inference! EXAMPLE-2 INCOMPLETE DEDUCTION Typical in observational studies, because authors may only report the outcomes of interest, which may be a subset of all the outcomes examined Llena C, Forner L. Caries Res 2008;42:387-93. Dietary habits in a child population in relation to caries experience EXAMPLE-2 INCOMPLETE DEDUCTION Llena C, Forner L. Caries Res 2008;42:387-93 Dietary habits in a child population in relation to caries experience Authors’ inference It can be concluded that the results of the present study suggest that the intake frequency of foods rich in semihydrolyzed starch (whether or not combined with sugar) and of sugary drinks are factors which are positively associated with caries experience in children from 6 to 10 years old, irrespective of age, sex and tooth-brushing frequency. Surprisingly… the average weekly consumption frequency of sticky sugar-rich foods is not a caries risk factor in the population studied EXAMPLE-2 INCOMPLETE DEDUCTION Llena C, Forner L. Caries Res 2008;42:387-93 Dietary habits in a child population in relation to caries experience Petti S. Caries Res 2009;43:78-9 Candies and jellies for caries prevention? EXAMPLE-2 INCOMPLETE DEDUCTION Petti S. Caries Res 2009;43:78-9 Candies and jellies for caries prevention? Good Inference: Frequent intake of sticky sugar-rich foods, such as jellies and candies, would help prevent caries in primary schoolchildren Llena C, Forner L. Caries Res 2009;42:79 Obviously not This is not good inference WRONG INFERENCE TYPICAL OF CLINICAL TRIALS RCCTs are more likely than other studies to be free of bias Selected participants are enrolled to decrease the sources of bias DISTORTED ASSEMBLY Only a small fraction of participants have co-morbidities Most RCCTs do not/minimally involve women, older people and minority ethnic groups DECREASE OF EXTERNAL VALIDITY Under-representation will bias absolute effect estimates EXAMPLE-3 WRONG INFERENCE Sankaranarayanan R, et al. Lancet 2005;365:1927-33 Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial EXAMPLE-3 WRONG INFERENCE Sankaranarayanan R, et al. Lancet 2005;365:1927-33 Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial Authors’ inference: On the basis of our findings, oral visual screening has the potential to prevent at least 37 000 deaths from oral cancer worldwide every year If oral cancer kills 83 000 males annually If ¾ cancer cases are attributable to tobacco and/or alcohol Tobacco and/or alcohol would be responsible for 62 000 deaths for oral cancer among males annually If Mortality Rate Ratio among screened and not screened smoking/drinking males is 0.57 The annual prevented number of oral cancer deaths would be 36 000 EXAMPLE-3 WRONG INFERENCE Typical example of NO INFERENCE The most favourable result obtained from a sample was simply extended without adaptation to the study-population. In this case to the world population Situation regarding oral cancer in Kerala ≠ World Mortality for oral cancer in Kerala 30-45 x100,000 annually Global mortality for oral cancer [GLOBOCAN] 2.6 X100,000 Mortality in Kerala 10-20 times greater than in the rest of the World!!! Sensitivity of visual screening in the rest of the World drastically reduced due to the increase in False Negatives Mortality Rate Ratio in the World drops from 0.57 to ??? EXAMPLE-3 WRONG INFERENCE Statistical Inference Mortality Rate Ratio among screened and not screened is 0.57 in Authors’ sample Then the 95% Confidence Interval of Mortality Rate Ratio is 0.35 to 0.93 [reported by Authors] The annual prevented number of oral cancer deaths among males ranges between 54 000 [concordant with the Authors’ sentence at least 37 000 deaths] and 5 800 Good Inference: oral visual screening has the potential to prevent at least 5 800 deaths from oral cancer worldwide every year EXAMPLE-3 WRONG INFERENCE Kujan O, et al. Lancet 2005;366:1265-6 Screening for oral cancer Good Inference: The results of Sankaranarayanan and colleagues’ study do not change the conclusion of our earlier Cochrane review that there is insufficient evidence to support or refute the introduction of population-based screening programmes for oral cancer worldwide Why do you see the speck in your brother's eye but fail to notice the beam in your own eye? Petti S, Scully C. Oral Oncol 2005;41:828-34 Oral cancer: The association between nation-based alcohol-drinking profiles and oral cancer mortality Why do you see the speck in your brother's eye but fail to notice the beam in your own eye? Petti S, Scully C. Oral Oncol 2005;41:828-34 Oral cancer: The association between nation-based alcohol-drinking profiles and oral cancer mortality Authors’ Inference: In conclusion, the results of the present study suggest that a high fraction of oral cancer deaths is attributable to heavy alcohol consumption and that this effect would be higher for spirit Paper cited 27 times Why do you see the speck in your brother's eye but fail to notice the beam in your own eye? Petti S, Scully C. Odontology 2010;98:144-52 Determinants of oral cancer at the national level: just a question of smoking and alcohol drinking prevalence? Why do you see the speck in your brother's eye but fail to notice the beam in your own eye? Petti S, Scully C. Odontology 2010;98:144-52 Determinants of oral cancer at the national level: just a question of smoking and alcohol drinking prevalence? Good Inference: oral cancer mortality may benefit from the improvement of the efficiency of health-care systems, and of the general economical, cultural, and social conditions of the population, in line with the principles of the Ottawa Charter for Health Promotion CONCLUSIONS Good Inference requires that 1.the study is well designed 2.the results are completely reported 3.the necessary limitations are adopted before extending the results to the general population
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