CLINICAL DECISION USING AN ARTICLE ABOUT TREATMENT JOSEFINA S. ISIDRO LAPENA MD, MFM, FPAFP PROFESSOR, UPCM

Transcription

1 CLINICAL DECISION USING AN ARTICLE ABOUT TREATMENT JOSEFINA S. ISIDRO LAPENA MD, MFM, FPAFP PROFESSOR, UPCM

2 Principles of Decision Making Knowing the patient s true state is often unnecessary Does my patient have a particular disease? In making the diagnosis, conceptualize the patient having the disease as a probability along a continuum between 0 [absolutely no disease] and 1 [absolutely with the disease]

3 Principles of Decision Making Treatment error is always a possibility when the diagnosis is uncertain It could involve mistakenly treating someone who does not have the disease or failing to treat someone who does have it. There are trade offs - risks and benefits between treating or not treating those with or without the disease

4 Principles of Decision Making The need for diagnostic certainty depends on the penalty for being wrong How certain do you need to be that someone has the disease before you are willing to label the patient and give treatment? If the benefit of treatment is high and the risks are low, one maybe willing to treat even if the probability is low

5 Decision Making in Medicine The main issue is making choices Diagnosis Should I request for a laboratory examination or treat right away? Between two diagnostic alternatives, which one should I request? Treatment Should I start treatment or observe first? Between two or more drugs, which one should I prescribe?

6 Focus on treatment

7 Treatment = any type of intervention Giving drugs Performing surgery Doing counseling Raising taxes on cigarette Fluoride in the water treat No treat With disease positive Negative Without disease Negative positive

8 Decision Making in the TRADITIONAL Paradigm Pathophysiology learned in medical school Experience - the other EBM Experts clinical practice guidelines

9 The Patient A 72 year old female widow hypertensive with a history of an episode of angina in the past followed up at your clinic and was found to have a slightly elevated cholesterol= 5.8 mmol/li. During your discussion on cardiac risks, she inquires if there is really a need to take an anti-cholesterol drug. Will it prevent her from getting a heart attack? What advise will you give?

10 Decision Making in the Old Paradigm! Pathophysiology! Hypercholesterolemia promotes coronary artery disease thus cholesterol is a risk factor! Experience! You have patients in the past who benefited from anti cholesterol drugs! Experts! National Cholesterol Education Program: screen all adult patients and intervene when necessary

11 Decision Making in the New Paradigm Medical Evidence

12 Decision Making in the New Paradigm Formulate the problem into an answerable question Conduct a systematic medical literature search Critically appraise the medical literature Apply the results Evaluate the application

13 Formulate the searchable problem Population Intervention Outcome Methodology

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15 The EBM Practitioner EBM practitioner Among elderly patients with hypertension with minimally elevated cholesterol, will anti-cholesterol drug decrease likelihood of heart attack / AMI in an RCT?

16 Volume 361, Issue 9364, 5 April 2003, Pages Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-thanaverage cholesterol concentrations, in the Anglo- Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial Björn Dahlöf, MD b, Prof Neil RPoulter, FRCP a,,, Hans Wedel, PhD c, Gareth Beevers, FRCP d, Mark aulfield, FRCP e, Rory Collins, FRCP f, Sverre E Kjeldsen, MD g, Arni Kristinsson, MD h, Gordon T McInnes, FRCP i, Jesper Mehlsen, MD j, Markku Nieminen, FRCP k, Eoin O'Brien, FESC l, Jan Östergren, MD m, for the ASCOT investigators

17 Methods Of hypertensive patients (aged years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, with non-fasting total cholesterol concentrations 6 5 mmol/l or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipidlowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being non-fatal myocardial infarction and fatal CHD. Data were analysed by intention to treat.

18 Is the article a match to the clinical scenario? Is the objective of the article similar to your clinical dilemma? Will it answer the questions you actually want answered?

19 Is the article a match to the clinical scenario? Is the objective of the article similar to your clinical dilemma? YES. The present trial was designed to evaluate the effect of cholesterol lowering with atorvastatin on occurrence of non fatal myocardial infarction and fatal CHD.

20 Are the Results Valid! Was the assignment of patients to treatments randomized?

21 Randomized Controlled Trials! provide the best evidence of effectiveness! individuals are randomly assigned (randomization) to either of the two or more groups! randomization tries to make the two groups similar! they are observed forward in time and their outcome compared! the outcome can be the cure of a disease, relief of symptoms or improvement in quality of life

22 ASCOT-LLA Blood lipid concentrations before randomisation determined whether patients were eligible for randomisation into the lipid group. Patients with a nonfasting total cholesterol of 6 5 mmol/l or less currently untreated with a statin or fibrate, and whose physicians did not intend to treat them with a statin or fibrate were randomly assigned by computer, with use of minimisation procedures at the appropriate coordinating centre, atorvastatin 10 mg daily or matching placebo.

23 Are the Results Valid! Was the assignment of patients to treatments randomized?! YES -. There was adequate randomization

24 Are the Results Valid! Were all patients who entered the trial properly accounted for and attributed at its conclusion?!check out drop out rates

25 ASCOT LL The study was stopped prematurely after patient years of follow-up (median 3 3 years). At the close of follow-up for the lipid-lowering arm, complete information was obtained on (98 8%) of the patients originally randomised. Data were analysed by intention to treat.

26 Are the Results Valid Were patients, health workers and study personnel blind to treatment? Blinding is the process by which the intervention being given is concealed from the patient, the clinicians and the one who analyzes the data. Patients, clinicians and data analysts are likely to have an opinion regarding the experimental treatment. These opinions, whether optimistic or pessimistic, can systematically distort reporting of treatment outcomes. As to avoid these reporter and observer bias, blinding is necessary.

27 Are the Results Valid Were patients, health workers and study personnel blind to treatment? In the main study the methodology mentioned that study was double blind placebo controlled

28 Are the Results Valid Were the groups similar at the start of treatment? YES Table 1 of the results section showed no major difference in the baseline characteristics between the two groups.

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30 Are the Results Valid Aside from experimental intervention, were the groups treated equally? Interventions other than the treatment under study, when differentially applied to the treatment and control groups, are called co-interventions. This might distort the results since they in themselves might cause changes in reported outcomes.

31 Are the Results Valid Aside from experimental intervention, were the groups treated equally? YES There were no planned co-intervention for the two groups

32 Findings Treatment was stopped after a median follow-up of 3 3 years. By that time, 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group (hazard ratio 0 64 [95% CI ], p=0 0005). This benefit emerged in the first year of follow-up. There was no significant heterogeneity among prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121 placebo, 0 73 [ ], p=0 024), total cardiovascular events (389 vs 486, 0 79 [ ], p=0 0005), and total coronary events (178 vs 247, 0 71 [ ], p=0 0005) were also significantly lowered. There were 185 deaths in the atorvastatin group and 212 in the placebo group (0 87 [ ], p=0 16). Atorvastatin lowered total serum cholesterol by about 1 3 mmol/l compared with placebo at 12 months, and by 1 1 mmol/l after 3 years of follow-up.

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34 What are the Results How large was the treatment effect? Atorvastatin Placebo Non fatal MI +/- fatal CHD Coronary events Mortality

35 ! Risk in Control (Rc) = Bad outcome in control group Total # of pts in control group! Risk in Treatment (Rt) = Bad outcome in treatment group Total # of pts in treatment group! Relative Risk (RR) = Rt/Rc

36 RELATIVE RISK Primary end point non fatal MI with or without fatal CHD RR = 1.9/3.0 = 0.63

37 Considering the negative effect or the risk and remembering ratio is treatment / control RR = 1 - no association or no effect RR > 1 = harmful effect RR < 1 = beneficial effect

38 RRR RELATIVE RISK REDUCTION [ 1 RR ] Indicates the percentage the likelihood of a bad outcome is reduced in the treatment group compared with the control group. ABSOLUTE RISK REDUCTION = ARR [ Rc Rt ] Indicates the actual amount of benefit a patient will get because of the treatment ARR and RRR are usually expressed in percent and interpreted as follows: > 0% - treatment is beneficial 0% - treatment has no effect < 0% - treatment is harmful

39 ! Absolute Risk Reduction (ARR) = Rc Rt = = 1.1! Relative Risk Reduction (RRR) = 1 RR = = 0.37

40 Precision

41 point. estimate within the. CONFIDENCE INTERVAL

42 What are the Results! How precise was the estimate of the treatment effect? EXAMPLES FOLLOW! Can be reported as:! 95% confidence interval Example 1: RR = 0.8 (95% CI: 0.2, 0.9) - We are 95% sure that the true effect of the drug/treatment lies within this range (between 0.2 to 0.9). - CI does not cross 1 =DEFINITE BENEFIT

43 ! Example 2: RR = 0.8 (95% CI: 0.5, 1.2) - We are 95% sure that the true effect of the drug/ treatment lies within this range (between 0.5 to 1.2). - CI crosses 1 = BENEFIT or HARM!Example 3: RR = 1.5 (95% CI: 1.2, 1.7) - We are 95% sure that the true effect of the drug/ treatment lies within this range (between 1.2 to 1.7). - CI does not cross 1 = DEFINITE HARM

44 ASCOTT LL The primary endpoint of non-fatal myocardial infarction, including silent myocardial infarction, and fatal CHD was significantly lower by 36% (hazard ratio 0 64 [95% CI ], p=0 0005) in the atorvastatin group than in the placebo group

45 What are the Results! How precise was the estimate of the treatment effect?! Can also be reported as p-value.! p is the probability that the observed differences are coincidental.! p<0.05! the probability that the observed effect is due to chance is less than 5%.!Also implies that the 95% CI of the RR does not contain the value of 1.0.

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47 Can the Results Help Me in Caring for My Patient Can the results be applied to my patient care? What will you look for?

48 Can the Results Help Me in Caring for My Patient Can the results be applied to my patient care? YES - subjects in this study included elderly hypertensive patients with angina normal to mildly elevated cholesterol

49 Can the Results Help Me in Caring for My Patient Were all clinically important outcomes considered? YES - The main outcomes considered were new non fatal MI, coronary death and overall cause of death

50 Can the Results Help Me in Caring for My Patient! Are the likely treatment benefits worth the potential harm and cost? NNT = 1/1.1 = 0.9 Total cost = NNT x dose x price x duration of treatment = (0.9)(1 tab/day)(18 pesos per tab)(365 days)(5 years) = PHP 29,863

51 The Patient What advise will you give?

52 Keep on Asking Keep on Searching Keep on Learning

53 thank you for your kind attention