Kliniske undersøgelsers hierarki Dirac kursus 4 b 30-3
Transcription
Kliniske undersøgelsers hierarki Dirac kursus 4 b 30-3
Kliniske undersøgelsers hierarki Dirac kursus 4 b 30-3-2005 Henrik E. Poulsen Professor, Overlæge dr.med. Klinisk Farmakologisk Afdeling Q7642 Rigshospitalet Tel 3545 7671 [email protected] she September 1999 http://www.themedweb.co.uk/didyouknow/ Zoneterapi Vaginal zoneterapi Skrevet af Camilla Kjems God sex er healende og en af forudsætningerne for et velfungerende forhold, mener Irina Andersen, der ved hjælp af vaginal akupressur kan afhjælpe problemer med underlivet og sexlivet. Eksempel på en forkert bøjet tommelfinger: Mange kvinder har problemer med underlivet og sexlivet. De døjer med krampe og svie og har måske svært ved at få orgasme. Irina Andersen er kvinden, der tager over, hvor mange læger giver op. Hun kan som den eneste i Danmark behandle med den gamle tantriske behandlingsform vaginal akupressur. Vaginal accupressur Ligesom zoneterapi forløser vaginal akupressur fysiske og psykiske problemer ved hjælp af tryk med fingrene. Men hvor zoneterapiens tager udgangspunkt i fødderne, arbejder den vaginale akupressur med tryk indeni og udenpå skeden, på hofterne lænden og ryggen. – Hvor huden under fødderne er meget grov, er vaginaen noget af det fineste, hvilket betyder, at denne behandling er meget effektiv, fortæller Irina. Eksempel på en rigtig bøjet tommelfinger: Vaginal akupressur kan afhjælpe: - Krampe, svie og kløe i skeden - Ubehag ved elskov - Skedekrampe - Problemer med at få orgasme - Problemer i forbindelse med fødsel og graviditet - Tilbagevendende svamp og blærebetændelse - Incest- og overgrebsproblematikker Stort erotisk potentiale Selvom det er en meget intim behandlingsform, oplever kvinderne, der kommer hos Irina, det sjældent som noget ubehageligt. Vi er da meget mere objektive I vores aktuelle moderne behandling ? Diabetes today (Type II, NIDDM) Treatment: Dietary counseling and a strict diet, insulin sensitizers/secretion stimulants Diabetes units are manned with doctors and dieticians There are no physiotherapist and no training centres Diabetes is a muscle disease ! Diabetes and impaired glucose tolerance: main reason is lack of exercise Exercise in the untrained can double or triple insulin sensitivity Hvorledes rankeres (videnskabelig) evidence ? Adams H, Brott T, Furland A, Gomez C, Grotta J, Helgason C et al. Guidelines for the managment of patients with acute ischemic stroke. Astatement for healthcare professionals from a special writing group of the stroke counsil, American Heart Association Stroke 1994; 25:1901-14 Kaste M, Olsen TS, Orgogozo J-M, Bogousslavsky J, Hacke W for the EUSI Excecutive Committee Organization of stroke care, Education, Stroke Units and Rehabilitation Cerebrosvasc Dis 2000;10(suppl 3): 1-11 The hierarchy of clinical evidence: Level I: Highest level of evidence primary endpoints from randomized, double-blinded study with adequate sample size properly performed meta-analysis of quality outstanding randomized trials Level II: Intermediate level of evidence randomized, non-blinded trials small randomized trials pre-defined secondary end-points of large randomized trials Level III: Lower level of evidence prospective case series with concurrent or historical control epidemiology post hoc analyses of randomized trials governmental or other public clearing reports Level IV: undetermined level of evidence case reports small case series without control general agreement despite lack of scientific evidence from controlled trials TABLE 1. GRADES OF EVIDENCE FOR THE PURPORTED QUALITYOF STUDY DESIGN * I Evidence obtained from at least one properly randomized, controlled trial. II-1 Evidence obtained from well-designed controlled trials without randomization. II-2 Evidence obtained from well-designed cohort or case–control analyticstudies, preferably from more than one center or research group. II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence. III Opinions of respected authorities, based on clinical experience; descriptivestudies and case reports; or reports of expert committees. *The grades are those of the U.S. Preventive Services Task Force. 2nd ed. Baltimore: Williams & Wilkins, 1996 Concato J, NEJM 2000;342:1887-92 Why Control ? Why Randomization One statistician to another: How’s your wife? Compared to what ! Disease activity Nosocomial border spring autumn Time Randomized controlled clinical trials: What happens if we treat patients ? (take patients, treat and see if they are better than non-treated) ex. Treat patients with lipid lowering drugs or placebo ex. Beta-carotene induces lung cancer in drinking smokers Epidemiology (cohort studies): Which characteristics do survivors show ? establish a cohort, ask how much they exercise, monitor survival ex. American Physician Health study ½ hour exercise daily gives lower CVD ex. High intake of beta-caroten in diet is associated with low CVD ex. Low body weight in high age is associated with poor survival is it dangerous to diet at high age ? BMJ 1996;312:71-72 (13 January) Editorials Evidence based medicine: what it is and what it isn't “It's about integrating individual clinical expertise and the best external evidence” “Evidence based medicine, whose philosophical origins extend back to mid-19th century Paris and earlier, remains a hot topic for clinicians, public health practitioners, purchasers, planners, and the public.” “the Cochrane Collaboration and Britain's Centre for Review and Dissemination in York are providing systematic reviews of the effects of health care; new evidence based practice journals are being launched; and it has become a common topic in the lay media” “Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients” “Evidence based medicine is neither old hat nor impossible to practice” ”Errors” in clinical trials: The classical errors: Type I and Type II errors difference due to chance, overse a true difference Other errors Type III erors: Wrong statistical method Wrong patient group Wrong diagnosis Wrong primary variable Wrong design …… Wrong strategy (commercially inspired) Wrong comparison (placebo ? best available treatment? …… no ”intention to treat analysis” Type IV errors: Doing the study for the ”wrong reasons” Publication bias: Bekelman JE JAMA. 2003;289:454-465. Data Synthesis Aggregating the results of these articles showed a statistically significant association between industry sponsorship and pro-industry conclusions (pooled Mantel-Haenszel odds ratio, 3.60; 95% confidence interval, 2.63-4.91). Industry sponsorship was also associated with restrictions on publication and data sharing. The approach to managing financial conflicts varied substantially across academic institutions and peer-reviewed journals. Conclusions Financial relationships among industry, scientific investigators, and academic institutions are widespread. Conflicts of interest arising from these ties can influence biomedical research in important ways. Comparing risks Relative risk Odds ratio prospective study retrospective study RR= a/(a+c) b/(b+d) OR = ad/bc Prospective classification Retrospective classification Yes No Gr 1 a c a+c Gr 1 b d b+d a+b c+d To what degree is evidence based medicine practiced in Denmark ? No certains estimates: Qualified guess: Hierachy of specialities: (prob heavy biassed) maybe about 10-25 % Cardiology (medical) Oncology (medical) Psychiatry anestesiology emergency medicine toxicology surgery Why power calculation (1 of 3) ? Simplified estimate of number of observations N1 = N2 = 2(t2α,df + tβ,df )2 x (CV2 / MERIDIF2) • • • • t-values can be obtained from a statistical t-table, SD is the standard variation of the measurement MERIDIF is the Minimum RElevant DIfference. If N1 = N2 is large t-values are about 2 and 1.7. N1 = N2 = 2(2+1.7)2 x ( SD2 / MERIDIF2) = 27.4 x (SD2 / MERIDIF2) 30 x (CV2 / MERIDIF2) or 30 (CV /MERIDIF)2 [1] http://www.ebook.stat.ucla.edu/calculators/powercalc/ [2] http://www.davidmlane.com/hyperstat/power.html/ Statistica 6.0 N1=n2= 30x (0,2/0,2)2 = 30 (stat: 23) N1=n2= 30x (0,2/0,1)2 = 120 (stat: 86) Independent Sample t-Test: Sample Size Calculation Two Means, t-Test, Ind. Samples (H0: Mu1 = Mu2) N vs. Power (Alpha = 0,05, Es = -0,5) 110 Required Sample Size (N) 100 90 80 70 60 50 40 0,6 0,7 0,8 Power Goal 0,9 1,0 Why Number needed to treat (NNT)? NNT = 1 p1 – p2 NNT = number needed to treat to avoid one case p1 = observed incidence without treatment p2 = observed incidence with treatment Ex. Pneumococ vaccination p1= 20/100.000, 70% treatment effect, mortality 20% NNT = 7143 (sepsis); NT = 35.714 (death) Relation between sample size (SS) and NNT SS calculation for obtaining significant results NNT treatment ”efficacy” in public health terms, dependent on incidence and efficacy. If SS is very great one should consider if the trial should be done, and whether it is an efficient treatment NEJM 2000; 342:1887-92 Epidemiology versus controlled intervention studies z RCT observational Concato NEJM 342;25:1887-92 Antioxidant trials Epidemiology consistantly indicate cancer and CVD protection RCT gives conflicting indication no effect positive effect negative effect The ALLHAT study Controlled trial (JAMA 288:2981-2997 and 2998-3007) diuretic chlorthalidone (Hygroton Novartis) Ca-blokker amlodipine (Norvasc, Pfizer) ACE-hæmmer lisinopril (Vivatec MSD, Zestril Zenica) chlorthalidone amlodipine lisinopril 12,5 – 25 mg 2.5 – 10 mg 10 -40 mg (0.25 – 0.50 kr [1999]) (0.75 – 3,00 kr) (1.15 – 4,60 kr) Initieret af NIH Pris US$ 125 mio Rekruitment Feb 1994 – March 31 2002 N 33.357 med hypertension + 1 CHD risiko faktor Outcome 1: fatal CHD, non-fatal AMI, intention to treat. 2: all-cause mortality, stroke, +++ Dec 9, 2002 Recent test results are startling. In the largest hypertension clinical trial ever conducted, an eight-year study involving more than 42,000 patients, a diuretic actually proved more effective than the newer drugs in lowering blood pressure and preventing cardiovascular complications. BMJ 2004, 326:170 Spind doctors soft pedal on antihypertensives: ALLHAT study JAMA 2002;288:2981-97 Ugeskrift for Læger · 14. april 2003, nr. 16 Har det offentlige en selvstændig forskningsmæssig rolle i lægemiddeludviklingen? STATUSARTIKEL Henrik Enghusen Poulsen & Thor Buch Grønlykke