First International Conference on Evidence- based healthcare (Pre-Conference Workshops on Topics related to Evidence Based Medicine) The Inaugural Conference of the International Society of Evidence-based Health Care When and Where? Workshops:06 October 2012 Conference:07 – 08 October 2012 Venue: India International Centre, New Delhi Contact

Who should attend? Physicians, Nurses, medical students involved in the implementation of evidence including frontline healthcare professionals Educators involved in teaching and training in evidence based healthcare Speakers Tony Dans, Kameshwar Prasad, Paul Glasziou Chile, Pakistan, Peru, Taiwan

Contact address: ISEHCON 2012 Clinical Epidemiology Unit Room No-91, Near Examination Section, All India Institute of Medical Sciences Ansari Nagar, New Delhi , India Phone: /

The First International Conference for Evidence-based Healthcare

Evidence-based personalized medicine: Plan for talk subgroup effects varying baseline risk values and preferences trial of therapy

Is there true variation in effects? Patients Severity/stage Intervention intensity/timing? Outcome? Short versus long-term

RR 0.67 RD 10% RR 0.67 RD 3.3% RR 0.67 RD 1%

Subgroup Analysis: The ISIS-2 Study ASAN=8587PlaceboN=8800 Overall Mortality 9.4%11.8% 11.1%10.3% 9.26%12% -23% +9% -28% Subgroup 1 Subroup 2

Subgroup Analysis: The ISIS-2 Study ASAN=8587PlaceboN=8800 Overall Mortality 9.4%11.8% 11.1%10.3% 9.26%12% -23% +9% -28% Gemini or Libra Other astrological signs

Sub-group hypotheses disproved Aspirin ineffective in secondary prevention of stroke in women Antihypertensives for primary prevention ineffective in women Antihypertensive treatment ineffective or harmful in elderly ACEI dont reduce mortality in CHF patients taking ASA ß blockers are ineffective after acute MI in elderly Thrombolysis for acute MI ineffective in previous MI Tamoxifen ineffective in breast cancer aged <50 years High-dose ASA better than low dose in carotid endarterectomy Amlodipine reduces deaths in non-ischaemic but not ischemic cardiomyopathy Platelet-activating factor receptor antagonist reduces mortality in gram- negative sepsis but not in other sepsis Ticlopidine better than ASA for recurrent stroke in blacks but not whites Valsartan reduces deaths in patients not receiving ACEI and beta blockers, but not in those who are

Patient presents with tibial fracture reaming, big nails more stable no reaming, small nails maintains blood supply could effect differ with fracture severity? open versus closed

Large RCT: SPRINT some patient open, some closed randomized to reamed/unreamed differences from prior trials concealed randomization blinded adjudication of outcomes proscription from re-operation for delayed union for six months 1319 randomized, 1226 (93%) followed 1 yr

SPRINT (stratified RRs)

Believe sub-group analysis – open vs closed tibial fractures? within-study comparison? yes large difference in effectyes unlikely chancep = 0.01 consistent across studies no a priori hypothesis yes one of small number hypotheses yes biologically compelling yes

Patients with atrial fibrillation risk of stroke varies CHADS2: congestive heart failure; hypertension; age >75; diabetes; prior stroke risk of stroke varies CHADs2 0: 8 per 1,000 per year CHADs2 1: 22 per 1,000 per year CHADS2: 45 per 1,000 per year CHADS3: 96 per 1,000 per year Warfarin 2/3 relative risk reduction CHADs2 0: 5 per 1,000 per year CHADs2 1: 14 per 1,000 per year CHADS2: 40 per 1,000 per year CHADS3: 64 per 1,000 per year

Comparison of patient and physician values to anticoagulate or not to anticoagulate patients with atrial fibrillation: differences between physician and patient perspectivesto anticoagulate or not to anticoagulate patients with atrial fibrillation: differences between physician and patient perspectives –Devereaux PJ et. al., BMJ, 2001 face to face interview of 63 physicians and 61 patientsface to face interview of 63 physicians and 61 patients probability trade-off tool to determine and compare physician and patient thresholds for how much stroke reduction is necessary and how much bleeding risk is acceptable for antithrombotic therapy in atrial fibrillationprobability trade-off tool to determine and compare physician and patient thresholds for how much stroke reduction is necessary and how much bleeding risk is acceptable for antithrombotic therapy in atrial fibrillation

Devereaux et. al., 2001 patients with atrial fibrillation at high risk of strokepatients with atrial fibrillation at high risk of stroke warfarin decreases risk at cost of increased gi bleedswarfarin decreases risk at cost of increased gi bleeds without treatment 100 patients will suffer:without treatment 100 patients will suffer: –12 strokes (six major, six minor), 3 serious gi bleeds in 2 years warfarin would decrease strokes in 100 patients to 4 per 2 years (8 fewer strokes, 4 major, minor)warfarin would decrease strokes in 100 patients to 4 per 2 years (8 fewer strokes, 4 major, minor) how many bleeds would you accept in 100 patients over a year, and still be willing to administer/take warfarin?how many bleeds would you accept in 100 patients over a year, and still be willing to administer/take warfarin?

Devereaux et. al., 2001 patients with to atrial fibrillation at high risk of strokepatients with to atrial fibrillation at high risk of stroke warfarin decreases risk at cost of increased gi bleedswarfarin decreases risk at cost of increased gi bleeds without treatment 100 patients will suffer:without treatment 100 patients will suffer: –12 strokes (six major, six minor), 3 serious gi bleeds in 2 years warfarin would decrease strokes in 100 patients to 4 per 2 years (8 fewer strokes, 4 major, minor)warfarin would decrease strokes in 100 patients to 4 per 2 years (8 fewer strokes, 4 major, minor) how many bleeds would you accept in 100 patients over a year, and still be willing to administer/take warfarin?how many bleeds would you accept in 100 patients over a year, and still be willing to administer/take warfarin?

Limitations of RCTs variable response if it worked, likely not in all didnt work, subgroup of responders with binary outcomes, most subgroup hypotheses (relative effects) spurious but symptomatic treatment presents opportunity

Conventional trial of therapy give medication, do you feel better? what are the problems? natural history placebo effects patient and physician expectations desire to please

Fibromyalgia chronic condition aches and pains fatigue sleep disturbance irritable bowel syndrome

N of 1 RCT – Ms. M.P. Amitriptyline 20 mg. o.d. Duration of periods: 4 weeks 3 pairs Outcomes: –weekly rating of symptoms energy level, tirednessenergy level, tiredness aches and painsaches and pains morning stiffnessmorning stiffness sleep disturbancesleep disturbance headachesheadaches bowel disturbancebowel disturbance

How much energy have you had in the last week? 1.No energy at all 2.A little energy 3.Some energy 4.Moderately energetic 5.Quite a bit of energy 6.Very energetic 7.Full of energy

When is N of 1 appropriate? you have a cold – N of 1? too short, not important enough you have appendicitis – N of 1? only once you have depression – N of 1? treatment takes too long chronic lung disease, bronchodilator – N of 1? chronic condition, symptoms important, medication acts fast, variable response

Personalizing EBM different relative effects (rarely) different absolute effects (usually) applying N of 1 principle (sometimes) individualized values and preferences (always) only the patient can tell you his/her values