Medical Statistics Joan Morris (j.k.morris@qmul.ac.uk) Professor of Medical Statistics Goldsmiths Lecture 2014.

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<ul><li>Slide 1</li></ul> <p>Medical Statistics Joan Morris (j.k.morris@qmul.ac.uk) Professor of Medical Statistics Goldsmiths Lecture 2014 Slide 2 Aims To give a brief description of some different areas of medical statistics Folic acid and Neural Tube Defects Screening for Heart Disease Slide 3 Folic Acid and Neural Tube Defects Slide 4 Can folic acid reduce neural tube defects (e.g. spina bifida) ? MRC Vitamin trial - randomised controlled trial Slide 5 Randomised Controlled Trial A clinical trial is an experiment in which a treatment is administered to humans in order to evaluate its efficacy and safety Controlled = a comparison group Randomised = allocated to groups on basis of chance e.g. tossing a coin (ensures fair comparison) Slide 6 Can folic acid reduce neural tube defects (e.g. spina bifida) ? MRC Vitamin trial - randomised controlled trial Large: 1817 women who had had a previous NTD, 33 centres, 7 countries Slide 7 Folic Acid vs Placebo for Neural Tube Defects Lancet 1991 Neural Tube Defects YesNoTotal Folic Acid Yes6587593 No21581602 Risk of NTD in treated group = Risk of NTD in control group = Relative Risk of NTD in treated group compared to control group = 1% 3.5% 1%/3.5% = 0.29 Slide 8 Folic Acid vs Placebo for Neural Tube Defects RR = 0.29 95% Confidence Interval : 0.10 to 0.76 P = 0.008 Slide 9 Can folic acid reduce neural tube defects (e.g. spina bifida) ? Results : Women who did not receive folic acid were 3 times more likely to have a second NTD pregnancy Impact : Women are advised to take folic acid PRIOR to becoming pregnant Slide 10 Slide 11 Statisticians Involvement Planning the study how large Analysing the results Stopping the study early (Independent Data Monitoring Committee) Slide 12 What Dose ? Women in MRC trial had had a previous NTD pregnancy and were given 4mg folic acid per day Current recommendation is 0.4mg folic acid per day Slide 13 Dose Folic Acid Serum Folate Level Risk of NTD pregnancy ? Slide 14 Slide 15 Slide 16 Dose Folic Acid Serum Folate Level Risk of NTD pregnancy Slide 17 Folic Acid and NTD Dose Response Slide 18 Slide 19 Interpretation The same proportional increase in serum folate has the same proportional reduction in NTD All women benefit from taking folic acid. There is not a threshold effect Slide 20 Conclusions Women planning a pregnancy should take 5mg folic acid tablets daily, instead of the 0.4mg dose presently recommended (THE LANCET Vol 358 December 15, 2001) Slide 21 MRC Trial Slide 22 Slide 23 Fortification (0.2mg/day) Slide 24 Use of Statistics in Screening Screening is the identification, among apparently healthy individuals, of those who are sufficiently at risk from a specific disorder to benefit from a subsequent diagnostic test, procedure or direct preventive action. Screening for Heart Disease Slide 25 Relative odds of major IHD event by fifths of the distribution of haemostatic and lipid markers for all men () and for men free of IHD at baseline examination ( ). Yarnell J et al. Eur Heart J 2004;25:1049-1056 The European Society of Cardiology Slide 26 AffectedUnaffected Biomarker : ZZ Slide 27 AffectedUnaffected Screen negative Screen positive Biomarker : ZZ Slide 28 Screen negative Screen positive Biomarker : ZZ False positives False negatives Slide 29 Risk Factor Unaffected Affected Good test Screening for a medical disorder Slide 30 Risk Factor Unaffected Affected Poor test Screening for a medical disorder Slide 31 Is Cholesterol any good for screening ? AffectedUnaffected Risk screen converter screen http://www.wolfson.q mul.ac.uk/rsc/ Slide 32 Detection Rate False Positive Rate Slide 33 Slide 34 4.2mm Hg Slide 35 Slide 36 7.5mm Hg Slide 37 Slide 38 Are there any good screening tests ? Antenatal screening for Downs syndrome Slide 39 Quadruple test markers Total hCG Inhibin-A AFP uE 3 Downs syndrome Unaffected Downs syndrome Unaffected Downs syndrome Unaffected Slide 40 1:10 8 1:10 6 1:10 4 1:10 2 1:1 10 2 :1 10 4 :1 Downs syndrome Unaffected Distribution of risk in Downs syndrome and unaffected pregnancies using AFP, uE3, total hCG and inhibin-A measured at 14-20 weeks (+ maternal age) Risk of a Downs syndrome pregnancy at term Slide 41 Method : Monte Carlo Simulation Generate a population of 500,000 people aged 0-89 years. [Use Office for National Statistics Population Data for England and Wales] Assign risk factors (eg diabetes, smoking, blood pressure) [Use Health of the Nation Survey] Calculate a persons risk [Use Framingham risk equations] Assign deaths according to peoples risks Slide 42 Slide 43 Conclusion Age is as good at predicting heart disease as measuring conventional risk factors Therefore treatment should be offered on the basis of age Slide 44 Treatment to Prevent Heart Disease Blood Pressure Lowering Drugs What dose Which drug Slide 45 Slide 46 Several studies looking at the same thing Each study may be relatively inconclusive because of too much uncertainty (too small) Meta-analysis : statistical method of combining and presenting results from several studies Can indicate more robust results Slide 47 Blood pressure reduction (mmHg) Slide 48 Major influence for prescription of combination therapy as first line of action 1 Drug Standard dose 3 Drugs Half standard dose 1 Drug Standard dose 3 Drugs Half standard dose 7 mm Hg 20 mm Hg10% 4% Reduction in blood pressure People reporting side effects Slide 49 BMJ 2009;338:b1665 Slide 50 Slide 51 Slide 52 Slide 53 A reduction in blood pressure of 20mm Hg halves the risk of a CHD event or stroke regardless of the persons original blood pressure or their level of cardiovascular risk. This means that everyone at sufficient cardiovascular risk will benefit from a reduction in blood pressure, even if they dont have a high blood pressure. For example all people with diabetes should be offered treatment. BMJ 2009;338:b1665 Slide 54 Slide 55 Slide 56 Slide 57 Involvement of Statistician Study design for clinical trial Analysing data from clinical trial Meta analysis from several trials Monte Carlo simulation using results above Slide 58 Conclusion As much about collection, interpretation and presentation as calculation Making sense out of uncertainty </p>

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