Evidensbaserad medicin Kritisk granskning, graderingssystem och checklistor Daniel Sjöberg
Grön syn
Formulera en PICO Hur vill ni designa er studie? Vilka utfallsmått vill ni ha? Grupp 1: Vad är detta för sjukdom? Grupp 2: Hur många drabbas? Grupp 3: Hur vet vi om man har denna sjukdom? Grupp 4: Är det här en farlig sjukdom? Grupp 5: Hur ska vi behandla sjukdomen? Grupp 6: Vad kommer det att kosta?
RRR, ARR och NNT En ny medicin har kommit mot benskörhet. En randomiserad kontrollerad studie har utförts med 100 patienter i behandlingsgrupp och 100 patienter i placebogrupp. 10 patienter i behandlingsgruppen fick en fraktur. 50 patienter i placebogruppen fick en fraktur. Behandling Placebo Fraktur 10 50 Inte fraktur 90 50 http://ktclearinghouse.ca/cebm/practise/ca/calculators/statscalc
RRR, ARR och NNT Absolut risk (AR) = Händelser Antal individer Behandling Placebo Fraktur 10 50 Inte fraktur 90 50 http://ktclearinghouse.ca/cebm/practise/ca/calculators/statscalc 10/100 = 0,1 50/100 =0,5
RRR, ARR och NNT Relativ risk (RR) = AR intervention AR kontroll 20% risk att få en fraktur vid behandling jämfört med placebo http://ktclearinghouse.ca/cebm/practise/ca/calculators/statscalc Behandling Placebo Fraktur 10 50 Inte fraktur 90 50 0,1/0,5= 0,2 = 20 %
RRR, ARR och NNT Relativ riskreduktion (RRR) = (AR kontroll AR intervention ) AR kontroll Behandling minskar risken för fraktur med 80% jämfört med placebo Behandling Placebo Fraktur 10 50 Inte fraktur 90 50 http://ktclearinghouse.ca/cebm/practise/ca/calculators/statscalc (0,5-0,1)/0,5 = 0,8 = 80 % [95% CI:0.63-0.89]
RRR, ARR och NNT Absolut riskreduktion (ARR) = AR kontroll AR intervention Behandling Placebo Vid behandling sänker man risken att få en fraktur med 40% Fraktur 10 50 Inte fraktur 90 50 http://ktclearinghouse.ca/cebm/practise/ca/calculators/statscalc 0,5 0,1 = 0,4 = 40 % (95% CI:0.28-0.51]
RRR, ARR och NNT Numbers needed to treat (NNT) = 1 ARR Behandling Placebo Vi måste behandla 2 patienter för att 1 patient ska slippa fraktur Fraktur 10 50 Inte fraktur 90 50 http://ktclearinghouse.ca/cebm/practise/ca/calculators/statscalc 1/0,4 = 2
RRR, ARR och NNT Antal/arm Händelser kontroll Händelser placebo RRR ARR NNT 100 10 50 80% 40% 2 100 1 5 80% 4% 25 100 10 11 9,1% 1% 100
Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks. A total of 3086 adults aged 18 years or older with unstable angina or non-q-wave acute myocardial infarction. Patients were randomly assigned to receive treatment with atorvastatin (n=1538) or matching placebo (n=1548) between 24 and 96 hours after hospital admission. Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.
RRR, ARR och NNT RRR = 16% Om man tar atorvastatin har man 0,84 gånger risken att drabbas av en händelse Patienter med atorvastatin har 16% lägre risk att drabbas av händelse ARR = 2,6% För varje 1000 patienter som får atorvastatin kan 26 händelser undvikas NNT = 38 Du måste behandla 38 patienter för att en ska skyddas från en händelse
Viva la Evidence
Association between early stage colon neoplasms and false-negative results from the fecal immunochemical test. BACKGROUND & AIMS: The fecal immunochemical test (FIT) can identify patients with advanced colorectal neoplasms, but it also has a high rate of false-negative results. It would be helpful to characterize colorectal neoplasms that are not detected by FIT to aid in development of new tests. We characterized colorectal neoplasms from patients who had negative results from the FIT. METHODS: We analyzed data from 18,296 subjects who were screened for colorectal cancer by colonoscopy and the FIT at the Health Management Center of National Taiwan University Hospital from September 2005 through September 2010. We identified 28 with cancer. RESULTS: The FIT identified patients with cancer with sensitivity values of 78.6% (95% CI, 58.5%-91.0%).
Diagnostiskt test Association between early stage colon neoplasms and falsenegative results from the fecal immunochemical test. Cancer Inte cancer Pos FIT 22 752 Neg FIT 6 13500
Cancer Inte cancer summa Pos FIT 22 752 774 Neg FIT 6 13500 13506 summa 28 14252 Sensitivitet? 22/28 = 0,786 Specificitet? 13500/14252 = 0,947 PPV? 22/774 = 0,028 NPV? 13500/13506 = 1,000 LR+? Sens/(1-spec) 0,786/(1-0,947) = 14,83 LR-? (1-sens)/spec (1-0,786)/0,947 = 0,23
High Maternal Body Mass Index in Early Pregnancy and Risks of Stillbirth and Infant Mortality -A Population-Based Sibling Study in Sweden. Using nationwide data from the Swedish Medical Birth Register (1992-2011), we included all primiparous women with singleton births who also had a sister with a first birth during that time period. Compared with population controls with a normal BMI (18.5-24.9), stillbirth risk increased with increasing BMI: BMI 25-29.9: odds ratio (OR) = 1.51 (95% CI: 1.21, 1.89) BMI 30-34.9: OR = 1.77 (95% CI: 1.24, 2.50) BMI 35: OR = 3.16 (95% CI: 2.10, 4.76) The sister case-control analyses revealed similar results. Offspring of obese women (BMI 30) had an increased risk of infant mortality when population controls were used (OR = 2.41, 95% CI: 1.83, 3.16), and an even higher risk was obtained when sister controls were used (OR = 4.04, 95% CI: 2.25, 7.25). We conclude that obesity in early pregnancy is associated with increased risks of stillbirth and infant mortality independently of genetic and early environmental risk factors shared within families.
Fall-kontroll Risk Om risken att något händer är x Så är risken att något inte händer 1-x Oddset är förhållandet mellan risken att något händer respektive inte händer Odds är x / (1-x) Om risken är låg, så är odds och risk mycket lika Odds ratio är förhållande mellan två odds Odds för högt BMI och dödfödd delat med Odds för normalt BMI och dödfödd
RR och OR RR= risken för händelse i behandlingsgruppen risken för händelse i kontrollgruppen OR = odds för händelse i behandlingsgruppen odds för händelse i kontrollgruppen
HR Hazard ratio Tidsfaktor (tex överlevnadsanalyser) Antal händelser per tidsenhet delat med number at risk
http://ktclearinghouse.ca/cebm/practise/ca/calculators/statscalc
www.casp-uk.net/casp-tools-checklists
What are we to do when the irresistible force of the need to offer clinical advice meets with the immovable object of flawed evidence? All we can do is our best: give the advice, but alert the advisees to the flaws in the evidence on which it is based. www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/
GRADE Working Group SBU, Socialstyrelsen, WHO, Cochrane, BMJ