APLIKASI HASIL UJI KLINIK

Ruben Dharmawan Laboratorium Parasitologi dan Mikologi FKUNS

Clinical Scenario
You are the attending physician on duty when a poor 45 year old man presents to the emergency room of a general hospital in the Philippines. He has experienced severe chest pain for two hours, associated with clammy perspiration. Physical examination reveals a blood pressure of 110/70 mmHg, a heart rate of 92, a normal 1st heart sound and clear lungs. An electrocardiogram discloses 3mm ST segment elevation in the inferior leads.

As intravenous lines are placed, and the patient is prepared for admission to the coronary care unit, you consider whether you should offer this patient a thrombolytic agent. Though your response is that the impecunious patient cannot afford the treatment, you ponder the right course of action in a richer patient. As your duty ends that night, you resolve to prepare for the next patient admitted for an acute myocardial infarction (MI), by retrieving the best evidence on the use of thrombolytics.

Biologic Issues
1.Are there pathophysiologic differences in the illness under study that may lead to a diminished treatment response? 2.Are there patient differences that may diminish the treatment response?

Social and Economic Issues

1.Are there important differences in patient compliance that may diminish the treatment response? 2.Are there important differences in provider compliance that may diminish the treatment response?

Epidemiologic Issues
1.Do my patients have co-morbid conditions that significantly alter the potential benefits and risks of the treatment? 2.Are there important differences in untreated patients' risk of adverse outcomes that might alter the efficiency of treatment?

1.Are there pathophysiologic differences in the illness under study that may lead to a diminished treatment response?
a. Divergence in pathogenetic mechanisms. Contoh : Orang Negro responsif terhadap diuretik tetapi tidak responsif terhadap betablocker. b. Biologic Differences in the causative agent. Contoh : Malaria dengan variasi resistensi terhadap obat.

2.Are there patient differences that may diminish the treatment response? a. Differences in drug metabolism. Slow metabolizers vs rapid metabolizers. Hepatic N-acetyl transferase tinggi pada orang Asia sehingga kadar isoniazid, hydralazine dan procainamide. G-6-PDH terhadap sulfonamide.

b. Differences in immune response. Hemophilus influenza vaccine has a lower efficacy in Alaskan natives than in non-native populations. c. Environmental factors. Thyroid dysfunction differs in low versus high iodine environments.

3.Are there important differences in patient compliance that may diminish the treatment response? a. Resource limitations in a particular setting. b. Less obvious attitudinal or behavioral idiosyncrasies. patient compliance.

4.Are there important differences in provider compliance that may diminish the treatment response? Meliputi perlengkapan dan peralatan diagnostik, monitoring, intervention serta ketrampilan ahli medis/teknisi. Contoh : walaupun rheumatic atrial fibrillation cukup banyak ditemukan di negara2 Asia, hanya sedikit laboratorium mampu melakukan tes titrasi dosis warfarin.

5.Do my patients have co-morbid conditions that significantly alter the potential benefits and risks of the treatment? a. Competing diagnostic possibilities. Pneumonia in developing countries : pneumonia pada anak balita diterapi dengan antibiotik hasilnya baik, tetapi ternyata ada pneumonia akibat malaria yang tidak akan berhasil bila diobati dengan antibiotik.

b. Competing etiologies of outcome. Di Filipina di suatu RS angka kematian setelah pemberian streptokinase pada AMI tinggi karena ternyata banyak penderita disertai pneumonia with sepsis. Infark berat sering disertai atrial fibrilasi, bila diberi antikoagulan (warfarin) akan memperoleh keuntungan ganda.

6.Are there important differences in untreated patients' risk of adverse outcomes that might alter the efficiency of treatment?
NNT = Number Needed to Treat RR = Relative Risk RRR = Relative Risk Reduction ARR = Absolute Risk Reduction

NNT = jumlah pasien yang perlu diobati agar terdapat 1 efek samping = treatments efficiency = kebalikan dari ARR. Resiko tanpa terapi = 20% RRR 10% maka resiko jadi 18% Tiap 100 pasien ada pencegahan 2 (2%) Maka NNT = 100/2 = 50 Jika Resiko tanpa terapi 10%, RRR tetapi 10% maka NNT 100.

Contoh : Age standardized mortality rate for CHD di Jepang = 40/100.000 North Ireland = 414/100.000 10 x penurunan insidens menyebabkan 10 x kenaikan NNT obat pencegah kematian akibat CHD 10 kali penurunan efisiensi pengobatan Reconsideration of applying the results of a trial to low risk patients.

DISCUSSION
RESOLUTION

TERIMA KASIH