Pharmacoinformatics lecture 3 - PowerPoint PPT Presentation

Loading...

PPT – Pharmacoinformatics lecture 3 PowerPoint presentation | free to download - id: 6ec4f3-MmI3Y



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Pharmacoinformatics lecture 3

Description:

Pharmacoinformatics lecture 3 Mgr. Zden k Ku era, Ph.D. kucera.xf.cz – PowerPoint PPT presentation

Number of Views:75
Avg rating:3.0/5.0
Slides: 63
Provided by: Zden64
Learn more at: http://kucera.xf.cz
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Pharmacoinformatics lecture 3


1
Pharmacoinformaticslecture 3
  • Mgr. Zdenek Kucera, Ph.D.
  • kucera.xf.cz

2
Evidence Based Medicine - EBM
  • Definition
  • When good quality research evidence is used in
    conjunction with professionals skills and
    users/societys perferences to solve specific
    problems
  • is the conscientious, explicit and judicious use
    of current best evidence in making decisions
    about the care of individual patients
    integrating clinical expertise with the best
    available external evidence from systematic
    research
  • Sackett et al (1996)
  • ------------
  • Pharmacist self-medication, consultations with
    patient

3
Influence factors
evidence (EBM not all-powerful)
expectation
opinions
experience
finances
politics
laws
time
4
Factors influencing the clinicians decision
5
Why EBM?
  • we are often asked for help! we need to know,
    where to find relevant information
  • not possible to rely on more experinced colleague
  • not good to rely on monographs
  • By 1970, several studies had shown that
    thrombolysis (clot dissolving) drugs reduced the
    number of deaths from a heart attack.
  • The clinical value of thrombolysis ... remains
    uncertain.
  • Oxford Textbook of Medicine, 1987
  • postgraduate education not systematic
  • increase of new information, commercial
    information
  • we have not time
  • etc...

6
Advantages EBM
  • quick availability of new information
  • teach the art of critical appraisal of the
    literature
  • systematic review new methodology of review
  • objective guidelines
  • assessment of new therapies

7
Criticism of the EBM
  • EBM is an academic exercise for medical
    students (3-4 questions/patient do I have a
    time to search for evidence?)
  • RCT greenhouse population only because of
    ethics...?
  • Governments, hospitals and HMOs have used the
    jargon of EBM to justify decisions, directives,
    or incentives that are seen by clinicians as
    inappropriate.
  • Misuse of EBM by pharmaceutical companies
    half-truths
  • treatment of the patient (co-morbidity,
    polypragmasia, aging, lactation, gravidity,
    pediatrics)
  • EBM is seen by some to promote therapeutically
    nihilistic approaches to medical practice since
    critical appraisal of commonly used therapies
    often concludes that they provide little or no
    benefit e.g. cough - Over the counter cough
    medicines for acute cough cannot be recommended
    because there is no good evidence for their
    effectiveness. BMJ 2002324329
  • Guidelines impersonal, schematic ...
  • No evidence no treatment???
  • If I do not treat according to guidelines see
    you in a court?

8
Evidence-based practice
  • 5 STEPS
  • Formulate a good question
  • Look for evidence
  • Critically appraise what you find
  • Act on the evidence
  • Evaluate the results

9
Step oneFormulating questions
10
1. Formulation of question
  • A well formulated question allows you to search
    in the medical database

The three/four part question
Who/what (persons or problem) Intervention (treatment, exposure,test etc) Comparison (comparison intervention, if relevant) Outcome (effect, result diagnosis etc)
11
What is a good question?
12
1. Formulation of question - example
Component Question Example
Patient or problem Description of the group like my patient? I have 55 old man, after myocardial infarction, feeling tired by life...
Intervention The main intervention? antidepressants?
Comparison intervention Alternative? or not
Result What I hope to achive? decrease in mortality after IM?
13
Pubmed limits, MeSH, clinical queries
Use of selective serotonin reuptake inhibitors
in depressed patients who experience an acute MI
might reduce subsequent cardiovascular morbidity
and mortality.
14
Component Question Example
Patient or problem Description of the group like my patient? Woman back pain
Intervention The main intervention? ibuprofen
Comparison intervention Alternative? diclofenac
Result What I hope to achive? what is better?
"Back Pain"MeSH AND "Diclofenac"MeSH AND
"ibuprofen"MeSH AND Randomized Controlled
Trialptyp
Diclofenac-K 12.5 mg demonstrated superiority vs
placebo on the primary efficacy parameter and
almost all secondary initial dose outcomes. With
respect to the initial dose, diclofenac-K 12.5 mg
was also significantly superior to ibuprofen 200
mg on SPID-3.
Int J Clin Pharmacol Ther. 2003 Sep41(9)375-85.
15
http//www.jr2.ox.ac.uk/bandolier/booth/painpag/Ac
utrev/Analgesics/Leagtab.html - Oxford league of
acute pain - Bandolier
Další odkaz google.com - NNT ibuprofen
diclofenac evidence based http//www.aafp.org/afp/
20050301/913.html - American Family Physician
16
What kind of question did you formulate?
  • How many people have a this problem .?
  • Why do some people get this problem..?
  • How can we decide whether someone has this
    problem?
  • What can we do to prevent or cure ..?
  • What is the prognosis ?
  • How does it feel to .?
  • How can we understand ..?

17
Kinds of study design
  • Experimental
  • randomised controlled trials

Qualitative
  • Pre-experimental
  • pre and post tests
  • cohort studies
  • case control studies
  • Quasi-experimental
  • quasi-randomised controlled trials

18
Hierarchy of evidences
  • - Systematic review (meta-analysis)
  • -----------------------------
  • - Randomised clinical trial
  • - Cohort study
  • - Case-control study
  • - Cross-sectional study
  • - Case reports

19
Case reports
  • Description of disease, treatment, phenomenon in
    one selected patient
  • Can be summarised into case-series

Czech Republic http//www.zdn.cz/kazuistiky
20
Cross-sectional studies
Snap-shot in time Measure exposure and effect at
the same time
time of study conduction
population
random selection
exposed with disease
exposed without disease
not exposed with disease
not exposed without disease
http//ucebnice.euromise.cz/index.php?conn0secti
onepidemnodenode1
21
Case-control studies
-Population are defined by those with disease
(cases) and those without the disease (control).
-The level of exposure to a health hazard(s) is
measured in the two groups and compared.-What
health hazard has caused the cases?
time
direction of observation
exposed
cases with disease
not exposed
population
exposed
controls without disease
not exposed
http//ucebnice.euromise.cz/index.php?conn0secti
onepidemnodenode1
22
Case control studies
Controls (people with no disease)
23
Cohort studies
  • The population of study is defined by exposure to
    a health hazard
  • They are followed-up over time to observe
    incidence of disease in exposed and non-exposed

24
Cohort studies
25
A cohort study
  • A cohort (or follow-up or longitudinal) study
    is when a group of people exposed and a group of
    persons unexposed to a potential cause of disease
    are followed-up over time and the incidence of
    the disease in one group compared with the
    incidence in the other.

26
Randomised controlled trial
27
RCT randomized clinical trial
  • Clinical - experimental study on patient
  • Controlled experimental drug or procedure are
    compared with another drug, procedure, or placebo
  • Randomized - patients are divided into groups
    randomly
  • Double blind patient and doctor does not know
    what drug is used
  • Intention-to-treat calculating the results with
    the number of patients in the beginning of the
    study
  • Check
  • Diagnostic or screening tests
  • Treatment technique
  • Effectiveness and safety of of drug treatment

28
RCT results - Odds Ratio
29
Numbers needed to treat
  • Number of people on average needed to receive
    treatment to produce one additional beneficial
    outcome
  • http//www.healthcare.ubc.ca/calc/clinsig.html

30
Confidence Interval (CI) the uncertainty
factor, how sure are we about the results? -
the shorter the CI the more certain we are about
the results - if it crosses the line of 1 (no
treatment effect) the intervention might not be
doing any good and could be doing harm
31
The p-value
How often you would see a similar result by
chance, when actually there was no effect by the
drug or treatment.
0
1
Impossible
Absolutely Certain
p0.001 Very unlikely 1 in 1000 p0.05
Fairly unlikely 1 in 20 p0.5 Fairly
likely 1 in 2 p0.75 Very likely 3 in 4
32
RCT - Results
33
RCT Increase
Number of evidences per day
34
Why bother with reviews?
  • volume of literature is condensed
  • new information is made accessible
  • some reviews are extremely good and take
    considerable time to find all the information on
    one topic

35

Types of review
Reviews
36
The medical literature can be compared to a
jungle. It is fast growing, full of dead wood,
sprinkled with hidden treasure and infested with
spiders and snakes. Peter Morgan, Scientific
Editor, Canadian Medical Association
37
Systematic Review
  • Review of all literature
  • On particular topic
  • Systematically identified, appraised and
    summarised

38
(No Transcript)
39
Meta-analysis
  • Statistical synthesis of results of several
    studies, which dealt with the same question

40
Odds Ratio Graph (Blobbogram)
LEFT E S S
M O RIGHT E
41
Odds Ratio (Blobbogram)
42
Meta-analysis - blobbogram
43
!RCT caution!
  • generalizability not included children, aged,
    pregnant, in lactation, with other drugs etc.
  • e.g. RALES study spironolactone patients with
    serious heart failure normal kidney function
    practice mild heart failure kidny failure
    Consequence increased prescription of
    spironolactone caused many deaths due to
    hyperkalemia!
  • comparator better is usual care than placebo!
  • e.g. PROVE-IT study 80 mg of potent
    atorvastatinu vs. 40 mg of pravastatin
    surprised by results???
  • surrogate end-points measurable outcome
    measures
  • patients with cardiac arrhytmia were given
    encainide and flecainide, perfect effect to
    arrhytmias, but increase of mortality!
  • relative risk, absolute risk
  • group A 1 case from 100, B 2 cases from 100
    relative reduction 50 , NNT 100.
  • group C 1 case from 1 000 000, D 2 cases from
    1 000 000 relative reduction 50 , NNT 1 000
    000. see http//www.cebm.utoronto.ca/practise/ca/s
    tatscal/
  • confidence intervals 95 CI the result is
    between the border for 95 certainty

44
!RCT caution!
  • statistical vs clinical relevance
  • statistical significance does not neccessarily
    mean clinical significance (more patients
    better statistical significance)
  • Side effects overlook
  • COX2 cardiotoxic, but Merck (rofecoxib) does not
    care for years, COX2 prevented 5 ulcers from
    1000patients, but caused 6 cardiovascular events
    Side effects with frequency 11000 statistically
    undetectable.
  • combined measures in primary outcome of study
  • UKPDS 1 event 21 different parameters
    (death, infarction, nefropathy...)
  • primary end-point not significant, secondary
    significant
  • p 0,05 1 from 20 repetition can be mistake
    and I admit this! If 20 results 1 mistake very
    presumable
  • class effect
  • studie HOPE, PEACE, EUROPA ACEI are not the
    same!
  • influence of pharmaceutical companies
  • They fund so they often adjudicate the
    publication or analyse the data! Negative result
    publication bias... NEJM 3522202-2210 50 of
    CRO accept companies advices for publication

45
Step twoFinding Evidence
46
2. Finding the Evidence
Now merged with ACP
  • EBM books
  • EBM journals
  • EBM databases
  • EBM Guidelines

47
ACP Journal Club see bi.cuni.czABC
IndexEBSCO orEvidence Based Medicine Reviews
48
Cochrane collaboration
  • International non-profit independent organisation
    main aim development of Cochrane Library
  • Archie Cochrane founder
  • Why? Too much information, is there the
    possibility to sort? Aim development of the
    database of systematic review
  • 90 countries different centres language
    support
  • Collaborative Review Groups development and
    maintenance of systematic reviews
  • Mainly volunteers
  • http//www.cochrane.org/index0.htm

49
Cochrane Library main parts
  • The Cochrane Database of Systematic Reviews
    (Cochrane Reviews)A rapidly growing list of
    regularly updated summaries of the best available
    evidence prepared by members of the Cochrane
    Collaboration. The Database of Abstracts of
    Reviews of Effects (DARE)Other published reviews
    prepared by people outside of the Cochrane
    Collaboration.
  • The Cochrane Central Register of Controlled
    Trials (CENTRAL)Where to look if you want to
    track down the original studies the largest
    single source of controlled trials.

http//www.nicsl.com.au/cochrane/guide_data.asp -
bližší podrobnosti http//144.32.150.197/scripts/W
EBC.EXE/NHSCRD/start - DARE
50
  • Clinical Queries filters for selection of
    reviews and clinical trials

51
TRIP database (Turning Research into Practice)
  • http//www.tripdatabase.com/
  • TRIP searches a broad range of evidence-based
    health care-related websites including Bandolier
    (good for allied health) and Cochrane Library
    databases. Simple search. View articles one by one

52
SUMSearch that was some search!
  • http//sumsearch.uthscsa.edu/
  • Devised by the University of Texas Health
    Sciences Center at San Antonio.
  • Searches MEDLINE, DARE, an on-line textbook,
    usually the Merck manual, etc.
  • Uses MeSH thesaurus

53
guidelines
  • Document How to treat based on the newest
    evidences
  • Czech Republic
  • http//www.cls.cz/dp/index.htm CLS JEP
  • http//www.svl.cz/default.aspx/cz/spol/svl/default
    /menu/doporucenepostu/doporucenepostu SVL
  • -----------
  • World
  • National Guideline Clearinghouse -
    http//www.guideline.gov/ - USA
  • NICE - http//www.nice.org.uk/ - UK NHS
  • GIN www.g-i-n.net International network
  • The Agency for Quality in Medicine (AQUMED)
    www.leitlinien.de BRD
  • http//www.phac-aspc.gc.ca/dpg_e.html - Canada
  • etc.....!

54
Step threeCritical appraisal
55
3. Critical appraisal
  • Case report lt case-control study lt cohort study lt
    RCT lt systematic review (lt guideline)
  • CASP critical appraisal skills programme
    http//www.phru.nhs.uk/casp/critical_appraisal_too
    ls.htm

56
Step fourImplementing evidence
57
Context sensitive practice
Professional skills
Evidence
Context Senstive Practice
Context Sensitive Practice
Values, resources, policy
Patient knowledge and values
58
Step fiveEvaluating results
59
Evaluation
  • Practice can be evaluate through
  • your own reflection
  • quality assurance programmes
  • further research

60
Drug Information Centres (DIC)
  • http//www.napra.org/docs/0/95/157/164.asp -
    Canada - list
  • http//www.uh.edu/libn/drug.htm - example of
    information sources in DIC
  • http//www.shpa.org.au/docs/druginfo_int.html -
    !international register! of Drug Information
    Centres

61
DIC CR see Solutio www.medon.cz
  • Informace o farmaceutických prípravcích
    Farmaceutický informacní servis (Phoenix)
  • Vinohradská 72, 618 00 Brno
  • tel. 548 135 171
  • v.fricova_at_bm.phoenix.cz
  • Lékové informacní centrum (LIC)
  • Lékárna FN U sv. Anny v Brne Pekarská 53,
    656 91 Brno
  • tel. 543 182 175-7
  • tel./fax 543 211 429 premysl.cerny_at_fnusa.cz
    pavla.kuksova_at_fnusa.cz
  • Lékové informacní centrum
  • Katedra sociální a klinické farmacie, FaF
    UK v Hradci Králové Heyrovského 1203, 500 05
    Hradec Králové 5
  • tel. 495 067 452
  • fax 495 512 266
  • lic_at_faf.cuni.cz
  • Stredisko vedeckých informací (SUKL)
  • Šrobárova 48, 100 41 Praha 10
  • tel. 272 185 829, 272 185 333
  • fax 272 185 756
  • svi_at_sukl.cz, infs_at_sukl.cz
  • Lékové informacní centrum pri 3. LF

www.zdravcentra.cz formulár pro vložení dotazu
62
Drug agencies
  • Czech Republic
  • www.sukl.cz
  • EU
  • www.emea.eu.int
  • see human medicines
  • requires JAVAscript!
  • EPAR better than SPC!
  • USA
  • www.fda.gov
  • CDER
  • ----------
  • USA see http//www.cdc.gov/ ! description of
    different diseases
About PowerShow.com