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Tuntutan ProfesionalismePengobatan Penderita

Sjarif IsmailLaboratorium Farmakologi FK-UNMUL

Evidence-Based Medicine

Evidence Based Medicine (EBM)

• “Menggunakan segala pertimbanganbukti ilmiah (evidence) yang sahih yang diketahui hingga kini untuk menentukanpengobatan pada penderita yang sedang kita hadapi”.

• Merupakan penjabaran bukti ilmiahlebih lanjut setelah obat dipasarkan danseiring dengan pengobatan rasional.

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What is the level of evidence ? (LoE)

Tingkat Evidens:

I. Evidens yang didapat dari minimal satu RCTs .II-1. Evidens yang didapat dari non-RCTs.II-2. Evidens yang didapat dari penelitian kohort atau kasus

kontrol, terutama yang diperoleh lebih dari satu pusatatau kelompok penelitian.

II-3. Evidens yang diperoleh dari perbandingan tempat atauwaktu dengan atau tanpa intervensi. Contoh : uji yang tidak terkontrol yang menghasilkan hasil yang cukupmengejutkan seperti hasil pengobatan dengan penisilinpada tahun 1940 dapat dimasukkan dalam kategori ini.

III. Konsensus, penelitian deskriptif, pengamatan klinis.

How is LoE implemented in Recommendation Guidelines? (1)

• Levels of Evidence for Heart Failure:

– A. Data derived from multiple RCTs.

– B. Data derived from a single randomized trial or non-randomized studies.

– C. Consensus opinion of experts was the primary source of recommendation.

www.guidelines.gov/

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How is LoE implemented in Recommendation Guidelines? (2)

• Strength of Recommendation:

– Class I: Conditions for which there is evidence/general agreement that a given procedure/therapy is useful and effective.

– Class II: Condition for which there is conflicting evidence or divergence of opinion about the usefulness /efficacy of performing the procedure /therapy.

» Class IIa: in favor of usefulness

» Class IIb: usefulness is less well established

– Class III:Condition for which there is evidence/general agreement that a procedure/therapy is not useful/effective and may be harmful.

www.guidelines.gov/

How is LoE implemented in Recommendation Guidelines? (3)

• “The strength of evidence does not necessarily reflect the strength of recommendation. A treatment may be considered controversial although it has been evaluated in CTs; conversely, a strong recommendation may be based on years of clinical experience and be supported only by historical data or by no data at all”.

• Disini conflict of interest dari penilai dijaga ketat!!

www.guidelines.gov/

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Drug Safety in increased focus around the world

• Increasing number of drug withdrawals because of harmful effects (recently: Prepulsid, Posicor, Hismanal, Rezulin, Lipobay, etc).

• Scientific report on epidemic proportions of serious ADRs in hospitalized patients.

(Lazarou, JAMA 1998)

• Medical mistakes (45.000 deaths/annually) and medication errors (28%) are reported, including under-utilization of proven drug therapies. (US Institute of Medicine, 2001)

EBM sebenarnya merupakan cara ygbiasa dilakukan dalam proses penilaiansuatu obat baru yg akan dipasarkan.Disini malah diperlukan juga penilaiananimal dan in-vitro studies.

Perbedaannya:* Penilaian obat pra-pemasaranmempertimbangkan seluruh masyarakat, * EBM menimbang untuk satu pasien.

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EBM in terms of Benefit-Risk Ratio

• The seriousness of the problem to be treated

• The efficacy of the drug you intend to use

• The seriousness and frequency of possible adverse effects

• The efficacy of other drugs which might be used instead

• The safety of other drugs which might be used instead.

Bagaimana dokter bisa mengertiEBM ?

• Evidence perlu diterapkan padapenderita dg segalapenyakit/komplikasi-nya.

• Evidence berubah menurut perkem-bangan ilmu.

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The Knowledge Filter(H.H. Bauer, 1995)

Primary literature

How much is incorrect?

Correction of errors

Much of it is correct

(adapted)

Steps in the EBM process

1. Start with the patient and a need for information

2. Formulate a relevant, answerable question

3. Select the resource and conduct a search

4. Appraise the evidence for its validity and applicability

5. Return to the patient -- integrate the evidence

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1. Start with the Patient

• You Already have seen 6 kids under the age of 2 years with Otitis Media at your family practice. Your experience from Pediatric clinical rotations and your memory of Pediatric textbooks indicates that Amoxicillin for 10 days is the accepted treatment for this problem. But you are also acutely aware of the consequences of over-prescribing antibiotics and the possible adverse effects of the drug. You wonder if it is really necessary to treat every occurrence of Otitis Media with Amoxicillin, especially in this age group.

2. Formulate the question

• Patient

• Intervention

• Comparison

• Outcome

• Type of Question

• Study DesignRichardson,W.S., Wilson M.

ACP Journal Club 123:A12

Nov-Dec 1995

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study design

Formulate the question

• Patient Otitis Media, 2 yrs old

• Intervention Amoxicillin

• Comparison no meds, placebo

• Outcome reduce fever, pain, long term benefit

• Question therapy

• Study Design randomized, controlled clinical trial

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The well built clinical question is:

• In children under the age of 2 years presenting with Otitis Media, does Amoxicillin significantly reduce fever and pain faster with better long term results than no medication?

• It’s a therapy question and the best evidence would be an RCT.

3. Select the resource

• Ideal information resource:– Valid –contains high quality data

– Relevant –clinical applicable

– Comprehensive – has data on all benefits/harms

– User-friendly – quick, easy to access and use

• see EBM Resource List

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Conduct the Search

• MEDLINE

• TRIP Database– Cochrane

– POEMS

– ACP Journal Club

http://www.ncbi.nlm.nih.gov/pubmed/

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http://www.thecochranelibrary.com/view/0/index.html

http://www.tripdatabase.com/

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the evidence

4. Evaluate the evidence

• Validity

• Results

• Applicability to the patient

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Validity issues:

• Randomization

• Follow-up complete (80% or better)

• Blinding (concealed allocation)

• Baseline similarities

• Groups treated equally

Results of the evidence:

Persistent symptoms at day 4 were present in 59% of the children in the Amoxicillin group and 72% in the placebo group. There was a high rate of treatment failure in both groups after therapy was completed: 64% in the treated group and 70% in the placebo group.

Journal of Family Practice

May 2000

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Applicability of the evidence

• Same diagnosis

• Same age groups

• General practice population

• Study done in Netherlands

5. Return to the patient:Between 7 and 8 children aged younger than 2 years have to be treated with an antibiotic for 1 of them to receive a symptomatic benefit at 4 days compared with placebo. However, only a small

percentage (30% to 36%) will be completely symptom free 11 days after presentation, regardless of antibiotic treatment. Since antibiotic treatment is not completely benign and its benefits are minimal. Most children between the ages of 6 months and 2 years need not be treated with antibiotics.

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EBM menjembataniIlmu Kedokteran dan Hukum ?

• EBM mulai dibutuhkan juga oleh seoranghakim menentukan apakah suatupengobatan tertentu sudah benar dalampersidangan. Diperlukan “ilmu” (evidence) di belakang pertimbangan suatu testimoniseorang saksi ahli. (JAMA Vol. 283 No.21, June 2000)

• Juga, EBM menentukan harga sahampabrik obat, yang disebarkan mass media ekonomi.

• Namun, masih akan dijumpaiberbagai kendala, karena ilmupengobatan dan EBM sendiritidak sesederhana itu.

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(1) Sepuluh Pedoman Pengobatan Rasional :

1. Timbanglah manfaat-risiko dgn memperhitungkanprinsip “Primum non nocere”.

2. Gunakanlah pertama-tama obat yg paling “established”, dan kenalilah obat pilihan ini untuksetiap indikasi.

3. Gunakanlah obat pilihan yg anda ketahui paling baik efeknya.

4. Batasilah pemberian jenis obat seminimal mungkin

5. Sesuaikanlah dosis obat untuk setiap penderita.

(2) Sepuluh Pedoman Pengobatan Rasional :

6. Gunakanlah dosis efektif terkecil.

7. Pilihlah cara pemberian obat yg paling aman, tanpa mengurangi efektivitas.

8. Jangan memilih preparat terbaru, karenabarunya.

9. Janganlah ketinggalan menggunakan obat baruyang (lebih) baik.

10. Cocokkanlah kebenaran data promosi pabrikobat.

(Darmansjah, 1979)

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