1. “Victor Babes” UNIVERSITY OF MEDICINE AND PHARMACY TIMISOARA DEPARTMENT OF MEDICAL INFORMATICS 2005 / 2006

2. http://www.medinfo.umft.ro/dim/metodologie.htm

3. “Medical Scientific Research Methodology” “MCS” 2 nd Module Course 1

4. 1. Medical Information Object of the course 1. Medical Information Object of the course

5. 1.1. MEDICAL INFORMATION Pacient – Physician RelationPacient – Physician Relation Elementary Cycle of Medical ActivityElementary Cycle of Medical Activity Medical Information Used in Medical PracticeMedical Information Used in Medical Practice –DATA – individual character – facts studied by MEDICAL/HEALTH INFORMATICSstudied by MEDICAL/HEALTH INFORMATICS –KNOWLEDGE – general character – concepts studied by MEDICAL RESEARCH METHODOLOGYstudied by MEDICAL RESEARCH METHODOLOGY

6. 1.2. ELEMENTARY CYCLE OF MEDICAL ACTIVITY

7. 1.3. TYPES OF DATA QUALITATIVE – Anamnesis (descriptive)QUALITATIVE – Anamnesis (descriptive) NUMERICAL – Laboratory investigationsNUMERICAL – Laboratory investigations GRAPHICAL – Biosignals (ECG, EEG…)GRAPHICAL – Biosignals (ECG, EEG…) SOUNDS: PhonocardiogramSOUNDS: Phonocardiogram STATIC IMAGES: X-Ray, NMRSTATIC IMAGES: X-Ray, NMR DYNAMIC IMAGES – moviesDYNAMIC IMAGES – movies

8. 1.4. TYPES OF KNOWLEDGE a) Explicit knowledge –Formalized expressed in words, schemes, formulaeexpressed in words, schemes, formulae –Easy transmission (books, lectures) –Education b) Tacit knowledge –Personal experience skillskill –Difficult transmission –Training

9. 1.5. Relation between “knowledge” and “diagnosis/treatment” LOGICAL INFERENCELOGICAL INFERENCE –‘Classical’ Medicine STATISTICAL INFERENCESTATISTICAL INFERENCE –Evidence Based Medicine

10. 1.6. Object of “Medical Scientific Research Methodology” “Production of [explicit] knowledge = research“Production of [explicit] knowledge = research Research methodsResearch methods –Observational surveyssurveys clinical trialsclinical trials –Experimental laboratory studies - specificlaboratory studies - specific –Theoretical – modeling/simulation

11. 1.7. Research Activity Steps DocumentationDocumentation Study OrganizingStudy Organizing –Clinical Studies –Laboratory Studies –Theoretical Research [formalizing knowledge] Data ProcessingData Processing Presentation of resultsPresentation of results Writing scientific papersWriting scientific papers

12. 1.8. TYPES OF CLINICAL STUDIES -[Public Health Studies] -[Health Services Studies] -Evaluation of a Diagnostic Procedure -Evaluation of a Therapeutical Approach -Risk and/or Prognostic Factors Studies

13. 1.9. TYPES OF PAPERS: -original papers- book reviews -case studies- theses -reviews [editorials] Approach Modes –Descriptive –Analitical

14. I. TYPES OF STUDIES General Characteristics I. TYPES OF STUDIES General Characteristics

15. 2. DESCRIPTION OF A HEALTH PHENOMENON 2. DESCRIPTION OF A HEALTH PHENOMENON

16. 2.1. STEPS: - first step: data collection -does not explain causes -comparation with existing etalons 2.2 THE PROTOCOL: -Estabilishing target population -Pathological state definition -Choosing variabiles, scales, standards etc -Epidemiological indicators computation -Comparing with known indicators

17. 2.3. Mandatory Criteria in Descriptive Studies Representativity ofRepresentativity of –general (target) population –studied pathology Comparability :Comparability : –with results from other studies –variables and their measurement Utility :Utility : –Medical and scientific pertinence –Priorities –Efficiency for patients

18. 3. EVALUATION OF A DIAGNOSTIC PROCEDURE 3. EVALUATION OF A DIAGNOSTIC PROCEDURE

19. 3.1. PHASES 1. Determination of: –Method validity –Fiability influenced by inter and intra-observational reproducibility 2. Qualitative Assessment of the Test (Procedure) –Sensitivity / Specificity –ROC Curve (Receiver Operating Characteristic) Sn = f (1 – Sp) –Youden Index: Y = Sn + Sp – 1 (diagn.value)

20. 3.2. Classification table Test T+ T- D+ N 11 N 12 R 1 D- N 21 N 22 R 2 C 1 C 2 N Real CLASSIFICATION QUALITY ASSESSMENT

21. 3.3. PARAMETERS false negative = N 12false negative = N 12 false positive = N 21false positive = N 21 sensitivity SN = p(T+/D+) = N 11 / R 1sensitivity SN = p(T+/D+) = N 11 / R 1 specificity SP = p(T-/D-) = N 22 / R 2specificity SP = p(T-/D-) = N 22 / R 2 –inverse relationship between SN and SP positive/negative predictive values:positive/negative predictive values: PPV = p(D+/T+) = N 11 / C 1PPV = p(D+/T+) = N 11 / C 1 NPV = p(D-/T-) = N 22 / C 2NPV = p(D-/T-) = N 22 / C 2 accuracy AC = (N 11 + N 22 ) / Naccuracy AC = (N 11 + N 22 ) / N classification error rate ER = (N 12 + N 21 ) / Nclassification error rate ER = (N 12 + N 21 ) / N

22. 3.4. Test Assessment (practical):3.4. Test Assessment (practical): –PPV, NPV; AC, ER –Test D (detectability = AC 2 / AC 1 ) –Test V (validity = Y 2 / Y 1 ) 3.5. Index Evaluation3.5. Index Evaluation –CB = Cost – Benefit –CE = Cost - Efficiency

23. 4. EVALUATION OF A THERAPEUTIC PROCEDURE: CLINICAL TRIALS 4. EVALUATION OF A THERAPEUTIC PROCEDURE: CLINICAL TRIALS

24. 4.1. Definitions and Terms Def: CLINICAL TRIAL = clinical research technique for estimating the effect of a therapy, within an extremely restrictive methodological frameDef: CLINICAL TRIAL = clinical research technique for estimating the effect of a therapy, within an extremely restrictive methodological frame Estimating EFFICIENCY:Estimating EFFICIENCY: Comparison of the “treated group” with a “control” group (placebo) Terms:Terms: –Controlled clinical trial – with controls –Uncontrolled clinical trial – without controls

25. 4.2. Methodological Principles in “clinical trials” A) Exact Scope DefinitionA) Exact Scope Definition –Unilateral study (refer.), bilateral (2 treatments) B) Patient Groups DefinitionB) Patient Groups Definition –Samples selection: size, continuity, inclusion / exclusion criteria C) Comparison Modes:C) Comparison Modes: –Comparable groups, randomization, stratification –Definition of treatment & control type (no treatment, placebo, std) –Mentaining results quality (systematic errors elimination)

26. –Defining the general comparing plan: Parallel groups – each group = a schemeParallel groups – each group = a scheme Cross-over – automartor; order by randomozationCross-over – automartor; order by randomozation –Disadv: need of a stable pathology, objective evaluation criteria, wash-out periods Secquential – patients recruited for a longer period; stop at significant differences.Secquential – patients recruited for a longer period; stop at significant differences. D) Defining assessment criteriaD) Defining assessment criteria –Main criterion – conforming the objective E) Analysis mode and comparison interpretationE) Analysis mode and comparison interpretation Type of analysis, statistical tests, prognostic factorsType of analysis, statistical tests, prognostic factors

27. Comparability (avoid “bias”)Comparability (avoid “bias”) –Randomization – random numbers –Simple / Double Blind Studies “simple blind” – the patient does not know his/her treatment, the physician does“simple blind” – the patient does not know his/her treatment, the physician does “double blind” – neither the patient nor the physician know the allocation to a certain treatment group“double blind” – neither the patient nor the physician know the allocation to a certain treatment group

28. The “ideal” study:The “ideal” study: (simple, “cheap”, good results) (simple, “cheap”, good results) –Controlled –Randomized –Double blind –Parallel groups

29. 4.3. Writing the Protocol of a CLINICAL TRIAL It should be detailed; its precision is determining the quality of the study 1.Introduction : basic data describing the medical problem and the therapy under study 2.Scope : clear definition of the scope and of the objectives 3.Method : description of the general comparing plan 4.Groups: defining subjects/patients (inclusion and exclusion criteria), patient acceptance signature for each individual in the study

30. 5. Sample size – details on calculating should be included in the protocol 6. Selection: randomization method: when, how, type (even, stratified) 7. Treatments: a) Studied treatment: procurement method, physical- chemical properties, prescribinga) Studied treatment: procurement method, physical- chemical properties, prescribing b) Placebo or reference treatment: procurement, comparability (look, physical-chemical qualities etc)b) Placebo or reference treatment: procurement, comparability (look, physical-chemical qualities etc) c) Associated treatments: list of authorized substances, administration conditions, forbidden substances listc) Associated treatments: list of authorized substances, administration conditions, forbidden substances list

31. 8. Initial balance: list of necessary investigations for inclusion or prognostic factors for rejection, which will be studied in the trial 9. Evaluation criteria for the therapeutic effect: details on data collection, main criterion, secondary criteria 10. Surveillance mode : all subjects will be surveyed in the same manner, at the same intervals. The rhythm and content of control examinations shall be presented. Following features must be observed, and the conduct in such cases shall be detailed: a) Secondary effects b) Therapy break-up c) Lost during the study

32. 11.. Data analysis a) Statistical analysis methodology comprises the hazard evaluation, systematic errors and confusion factors, with alternate explanation for the recorded results b) The attitude on the lost shall be mentioned: the following postulate is recommended: “once randomized – mandatory analyzed”. None of the subjects included in a study group shall be omitted in the analysis 12. Criteria for breaking-up the trial a) Clear benefic results in an intermediary phase, due to a highly significance of the tests, correlated with the clinical context b) When the treatment may be dangerous for the subject(s)

33. 13. Attached documents The protocol has usually the following attached documents: List of persons and their responsibilitiesList of persons and their responsibilities Activities calendarActivities calendar Observation log:Observation log: –Subjects identification data –Inclusion data –Results of successive balances The informative document given to patientsThe informative document given to patients List of acceptance signaturesList of acceptance signatures Ethical commission approval, containing details on the trial quality control strategy, during the study, for subjects / patients protectionEthical commission approval, containing details on the trial quality control strategy, during the study, for subjects / patients protection

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