Mcs Tot

Metodologia cercetrii tiinifice
Concepte, necesiti i atitudini
Corin Badiu, 2007
Cercetarea stiintifica (1)

joaca un rol foarte important in eforturile medicinei de a mentine starea de sanatate si de a combate bolile ne ajuta sa obtinem cunostinte noi si sa dezvoltam instrumente adecvate pentru a fi utilizate pe baza cunostintelor existente

permite diagnosticarea si tratarea diverselor afectiuni ofera dovezi pe care sa se bazeze politicile sanitare si deciziile asupra sanatatii si dezvoltarii sistemelor de asistenta medicala

Desi OMS si statele sale membre sunt constiente de importanta cercetarii medicale, aceasta nu a fost o prioritate in multe tari in curs de dezvoltare
lipsa metodologiei de cercetare absenta cercetatorilor calificati sistemul de management si coordonare a cercetarii medicale fie:
nu a fost creat nu functioneaza adecvat
Procesul de cercetare
este piatra fundamentala pentru luarea unor decizii eficiente si in cunostinta de cauza este parte integranta din eforturile tarilor de: a ameliora starea de sanatate a populatiei si de
a creste eficienta sistemelor sanitare, mai ales in conditii de transformari dramatice epidemiologice, demografice si economice, transformari care afecteaza profund sistemele sanitare
In aceste cursuri:
se vor descrie metodele de planificare si realizare a cercetarii stiintifice:
formularea problemelor stabilirea obiectivelor cercetarii planificarea studiului ("designing the study")
metode de colectare a datelor analiza statistica a datelor
interpretarea rezultatelor diseminarea acestor rezultate
DEFINITII (1)
cercetarea stiintifica este o descoperire a cunostintelor prin cautare sau investigatie asidua sau prin experimente avand drept scop descoperirea si interpretarea de cunostinte noi metoda stiintifica este un grup de tehnici si proceduri sistematice aplicate in cursul desfasurarii investigatiei sau experimentului si orientate catre obtinerea de noi cunostinte
DEFINITII (2)
cercetarea si metodele stiintifice pot fi considerate o cale de investigatie critica ducand la descoperirea unor fapte sau informatii care amplifica intelegerea noastra asupra sanatatii si bolilor umane
CATEGORII ALE CERCETARII

1.Cercetarea Empirica si Teoretica 2.Cercetarea Fundamentala si Aplicata 3.Triunghiul Cercetarii in Domeniul Sanatatii
1.Cercetarea Empirica si Teoretica (1)

abordarea filozofica a cercetarii este in principal de doua tipuri:
Empirica Teoretica
cercetarea in domeniul sanatatii utilizeaza in principal abordarea empirica adica este bazata pe:
Observatie Experienta
Mai putin bazata pe: Teorie Abstractizare

cercetarea epidemiologica, de ex., depinde de colectarea sistematica a observatiilor fenomenelor legate de starea de santate care prezinta interes in cazul unei populatii definite

mai mult, chiar in cadrul abstractizarii prin modele matematice, NU pot fi obtinute progrese in intelegerea cauzelor si modului de aparitie a bolilor daca nu se face o comparatie a unor modele construite teoretic, cu ceea ce se observa concret la nivelul populatiilor

cercetarea empirica si teoretica se completeaza reciproc in dezvoltarea unei intelegeri a fenomenelor, in previziunea unor evenimente viitoare si in prevenirea unor evenimente daunatoare asupra bunastarii generale a populatiei de interes
Cercetarea empirica
Cercetarea empirica in stiintele medicale poate fi:
cantitativa calitativa
Cercetarea in Domeniul Medical (1)

In general cercetarea in domeniul medical utilizeaza informatii de tip cantitativ In majoritatea cazurilor aceasta implica identificarea:
populatiei de interes caracteristicilor (variabilelor) indivizilor (unitatilor) din populatie studierea variabilitatilor acestor caracteristici intre indivizii din populatie

De aceea cuantificarea cercetarii empirice se obtine prin trei procedee numerice interrelationate:
masurarea variabilelor estimarea parametrilor populatiei (parametri ai distributiei probabilitatii care surprind variabilitatea observatiilor in populatie) testarea statistica a ipotezelor, sau estimarea gradului in care "sansa" singura poate fi responsabila de variatia dintre indivizii sau grupurile aflate sub observatie

Luarea in considerare a sansei sau probabilitatii este substanta alcatuirii planului de cercetare (design-ului cercetarii)
mai mult decat orice, planificarea cercetarii trebuie sa tina seama de rolul sansei pentru a asigura validitatea metodele statistice sunt acelea care mentin legile probabilitatii in cursul cercetarii noastre

Metodele statistice:
permit analiza si interpretarea adecvate ale rezultatelor statistica ofera instrumentele care permit cercetarii medicale sa fie mai degraba empirica decat abstracta
ea ne permite sa ne confirmam descoperirile prin continuarea observatiei si experimentului
2.Cercetarea Fundamentala si Aplicata(1)

din punct de vedere functional cercetarea poate fi clasificata in:
fundamentala (sau pura sau bazala = "basic") aplicata

cercetarea fundamentala de obicei este considerata a implicata o cautare a cunostintelor fara definirea unei utilitati clare sau a unui scop specific cercetarea aplicata este orientata spre o anumita problema si este directionata catre rezolvarea unei probleme existente
2.Cercetarea Fundamentala si Aplicata(3) Exista o controversa continua cu privire la beneficiul relativ si contributia catre societate a celor doua tipuri de cercetare

unii considera ca stiinta, care depinde in mare parte de sprijinul societatii, trebuie sa se orienteze direct spre solutionarea unor probleme relevante ale omului, in timp ce altii pretind ca investigatia stiintifica este cea mai productiva atunci cand se efectueaza liber, fara nici o constrangere, iar cele mai mari progrese ale ale stiintei au rezultat din cercetarea pura

in general este recunoscut faptul ca e nevoie de un echilibru sanatos intre cele doua tipuri de cercetare, societatile mai bogate si mai avansate tehnologic fiind capabile de a sustine o proportie mai mare de cercetare fundamentala decat societatile cu mai putine resurse disponibile
3.Triunghiul Cercetarii in Domeniul Sanatatii (1)
trei categorii interconectate operational:

cercetarea biomedicala cercetarea serviciilor de sanatate (serviciilor medicale) cercetarea comportamentala
3.Triunghiul Cercetarii in Domeniul Sanatatii (2) Se realizeaza astfel asa-numitul triunghi al cercetarii medicale (al cercetarii in domeniul sanatatii)
3.Triunghiul Cercetarii in Domeniul Sanatatii (3) Cercetarea biomedicala se preocupa in principal de cercetarea fundamentala implicand procesele de la nivel celular

Cercetarea serviciilor de sanatate (a serviciilor medicale) are drept obiectiv mediul care il inconjoara e om si care determina transformari la nivel celular

Cercetarea comportamentala se preocupa de interactiunea dintre om si mediu inconjurator intr-o maniera reflectand credintele, atitudinile si practicile
individului in societate
Fundamentele Stiintifice ale Cercetarii (1)

mai multe principii fundamentale sunt utilizate in cercetarea stiintifica:
1.Ordinea 2.Deductia si Sansa 3.Evaluarea si Probabilitatea 4.Ipoteza

1.Ordinea (1)
Metoda stiintifica difera de "bunul simt" in ajungerea la concluzii prin utilizarea observatiei organizate a entitatilor sau evenimentelor care sunt clasificate sau ordonate pe baza proprietatilor si a comportamentelor comune Ordinea (2) acest caracter comun al proprietatilor si comportamentelor permite efectuarea de predictiuni care, duse la limita, devin legi

1.Deductia si Sansa
Gandirea, sau deductia este forta progreselor in cercetare
in termenii logicii, aceasta inseamna ca o afirmatie sau o concluzie trebuie sa fie acceptata deoarece una sau mai multe alte afirmatii sau premize (dovezi) sunt adevarate 2. Deductia si Sansa supozitiile, prezumtiile sau teoriile deductive pot fi atat de dezvoltate, printr-o constructie atenta, incat sa devina ipoteze testabile testarea ipotezei este metoda care sta la baza avansarii cunostintelor in stiinta 3.Deductia si Sansa in dezvoltarea deductiilor s-au diferentiat doua abordari sau argumente distincte: deductiva Inductiva 4.Deductia si Sansa in deductie, in mod necesar concluzia rezulta din premize, ca de exemplu in: silogism (toate A sunt B, toate B sunt C, de aceea toate A sunt C) ecuatiile algebrice

Deductia si Sansa (5)
deductia poate fi distinsa prin faptul ca se deplaseaza de la general la specific si NU permite elementele legate de sansa sau nesiguranta de aceea concluziile deductive sunt potrivite cercetarii teoretice

deoarece cercetarea medicala este primordial empirica, depinde aproape in totalitate de gandirea inductiva

in gandirea inductiva (1) concluzia NU rezulta neaparat din premize sau dovezi (fapte) putem afirma doar ca o concluzie are o probabilitate mai mare de a fi adevarata daca premizele sunt
adevarate, adica exista posibilitatea ca premizele sa fie adevarate, dar concluziile sa fie false
Deductia si Sansa (8) in gandirea inductiva (2) de aceea trebuie sa se tina seama in intregime de sansa
mai departe, gandirea inductiva se distinge prin faptul ca trece de la specific la general

3.Evaluarea si Probabilitatea(1)
Cerinta critica a efectuarii proiectului in cercetare, aceea care asigura validitatea, este evaluarea probabilitatii de la inceput pana la capat
cele mai importante elemente (1) ale proiectului de cercetare, elemente avand drept scop asigurarea integritatii probabilitatii si prevenirea bias-ului, sunt:
esantionul sa fie reprezentativ randomizarea in selectia grupurilor de studiu

cele mai importante elemente (2) ale proiectului de cercetare:
mentinerea grupurilor de comparatie sub forma grupurilor control realizarea principiului "dublu-orb" (atat a experimentelor cat si a subiectilor) utilizarea metodelor probabilitatii (statistice) in analiza si interpretarea rezultatelor
Probabilitatea (1) este o masura a nesigurantei sau a variabilitatii caracteristicilor intre diversii indivizi ai unei populatii:
daca se va observa intreaga populatie, calcularea frecventelor relative ale variabilelor ofera toate informatiile referitoare la variabilitate

Probabilitatea (2)
daca se va observa doar un esantion de indivizi din acea populatie, deductia de la esantion la populatie (de la specific la general) va implica identificarea:
probabilitatilor evenimentelor observate precum si a legilor probabilitatii care ne permit sa masuram nivelul de nesiguranta al deductiilor noastre

4.Ipoteza(1)
ipotezele sunt afirmatii atent construite referitoare la un fenomen intalnit intr-o populatie ipotezele pot fi generate fie prin:
rationament deductiv rationament inductiv rezultat din observatii anterioare

4.Ipoteza(2)
unul dintre instrumentele cele mai utile ale cercetarii medicale
este generarea ipotezelor care, cand sunt testate vor conduce la identificarea celor mai probabile cauze de boala sau de transformari in fenomenul observat

4.Ipoteza(3)
desi NU putem trage concluzii definitive sau sa pretindem ca avem dovezi bazandu-ne pe metoda inductiva, totusi ne putem apropia si mai mult de "adevar" prin eliminarea ipotezelor existente si inlocuirea lor cu unele avand o plauzibilitate si mai mare
Fundamentele Stiintifice ale Cercetarii (13) 4.Ipoteza(4)

in cercetarea medicala, ipotezele sunt adesea
construite si testate pentru a identifica niste cauze
ale unor boli si a explica distributia bolilor in populatii

4.Ipoteza(5)
in formularea ipotezelor legate de asociere si cauzalitate se
utilizeaza adesea canoanele gandirii inductive formulate de Mill
Pe scurt aceste metode includ:

metoda diferentelor metoda punerii de acord ("agreement") metoda variatiei concomitente, sau efectul doza-raspuns metoda analogiei

4.Ipoteza(6)
metoda diferentelor cand frecventa unei boli este foarte diferita in doua circumstante diferite, iar un factor poate fi identificat intr-o circumstanta si NU in cealalta, acest factor sau absenta lui poate fi cauza bolii
ex: diferenta in frecventa cancerului pulmonar la fumatori si nefumatori

metoda punerii de acord ("agreement") daca un factor, sau absenta lui este comuna unui numar de circumstante diferite care se constata ca sunt asociate cu prezenta unei boli, acel factor, sau absenta lui poate fi asociata cauzal cu boala
ex: aparitia hepatitei A este asociata cu venirea in contact cu un pacient, cu aglomeratia si cu igiena deficitara, fiecare contribuind la transmiterea virusului hepatitic

metoda variatiei concomitente, sau efectul dozaraspuns
exemple de variatie concomitenta:
cresterea expresiei gusei endemice paralel cu scaderea nivelului iodului in dieta (alimentatie) cresterea frecventei leucemiei odata cu marirea expunerii la radiatii cresterea prevalentei elefantiazisului in ariile cu o crestere a endemicitatii filariei

4.Ipoteza (9)
metoda analogiei distributia si frecventa unei afectiuni sau a unui efect pot fi suficient de similare cu acelea ale unei alte boli incat sa sugereze o cauza comuna
ex: infectia cu virus hepatitic B si neoplasmul hepatic
Ipoteza de lucru Organizarea studiului Tipuri de studii
Corin Badiu, 2011
Obiective
Construire unui mod de documentare, emitere de ipoteze si testarea acestora
Dobandirea abilitatilor de cercetare
Redactarea unui protocol de 10 pagini pentru un studiu real / ipotetic

Analiza altor studii (peer review)
Tipuri de Studii
Nu sunt cea mai buna alegere pentru acest curs Studii fundamentale: molecule, celule, soareci Cost-eficienta, meta-analize Cercetare calitativa Ideal Un studiu observational (sau interventional) ce implica pacienti
Sectiuni ale protocolului de studiu

Ipoteza de lucru Semnificatia (fondul) Designul studiului Populatia de studiu si recoltarea datelor; controlul de calitate al datelor Variabile si masuratori Analiza statistica a datelor Etica cercetarii medicale
Ipoteza de lucru
Toate studiile incep cu o problema, intrebare fara raspuns Scopul este alegerea unei intrebari de cercetare relevante, ce poate fi transformata in proiect
Problema studiului
Format pentru un studiu descriptiv
Intr-o populatie de [populatie de studiu ], care este prevalenta (sau incidenta, mortalitatea, etc.) [variabila dependenta]? Majoritatea studiilor au mai mult decat o problema de evaluat si rezolvat Protocolul de cercetare deriva din problema studiului
Problema studiului
Format uzual (studii analitice):
Intr-o populatie de [populatie de studiu], exista o asociere intre [variabila dependenta] cu [variabila independenta]?
Identificati problema studiului enuntata in rezumat

Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children. We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a randomized, double-blind study in Soweto, South Africa. At 6, 10 and 14 weeks of age, 19,922 children received the 9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197), and 19,914 received placebo
Klugman KP, Madhi SA, Huebner RE, et al. A trial of 9-valent pneumococcal conjugate vaccine in children with and without HIV infection. N Engl J Med 2003; 349:1341-8.
Intr-o populatie de [populatie de studiu], exista o asociere intre [variabila dependenta] si [variabila independenta]?
In a population of South African infants is immunization with a 9-valent pneumococcal conjugate vaccine associated with invasive pneumococcal disease?
Originile unei probleme de cercetare

Cercetarea literaturii
Discutia problemelor din literatura
A fi deschis la idei si tehnici noi

Importanta invatarii
Imaginatia
Caracteristicile unui studiu FINER

Fezabil Interesant pentru investigator Nou Etic Relevant
Caracteristicile FINER
Criterii de Fezabilitate
Numar adecvat de subiecti Expertiza technica adecvata Realizabil ca resurse de timp si bani Resurse umane calificate adecvat
Caracteristicile FINER
Criterii de Interes
Studii cu impact populational Detalierea a noi mecanisme de boala Studii de eficienta terapeutica pentru metode noi
Caracteristicile FINER Criterii de Noutate

Confirma sau anuleaza cercetari anterioare
Extinde cercetari anterioare Furnizeaza noi date
Caracteristicile FINER Criterii de Etica

Consimtamant informat !!! Protejeaza pacientii sau NU ii expune unui risc suplimentar Excluderea imediata / oprirea studiului in cazul unor efecte adverse severe
Caracteristicile FINER Criterii de Relevanta

Pentru cunoasterea stiintifica
Pentru clinicieni, sanatatea publica sau politicile de sanatate

Pentru directii de cercetare viitoare
Nefezabil
Probleme si solutii: Planul nu este FINER
Prea larg Prea putini pacienti disponibili Metode sofisticate, peste abilitatile dovedite de investigator Prea scump
Fara interes, noutate sau relevanta Evaluare etica inadecvata
Probleme si solutii:
Planul nu este Fezabil
Prea larg
Un set mai mic de variabile Se delimiteaza mai mult domeniul
Insuficienti subiecti disponibili

Extinde criteriile de includere Schimba criteriile de excludere Adauga alte surse de subiecti Extinde durata de inrolare Foloseste strategii de scadere a lotului
Probleme si solutii: Planul nu este fezabil

Metode in afara abilitatilor investigatorului
Colaborare cu colegi cu aptitudini Consultarea de experti si reluarea literaturii pentru metode alternative Invata si practica aptitudinile cerute de studiu
Prea scump
Scade costurile designului de studiu
Mai putini subiecti si masuratori Detaliu mai mic al masuratorii Mai putine vizite de urmarire
Neinteresant, vechi sau irelevant

Consulta mentorul Modifica problema cercetata
Probleme si solutii: Planul nu este FINER
Abordare etica nesigura

Consulta comitetul de etica Modifica intrebarea / designul
Probleme si solutii
Planul de studiu este vag
Rescrie planul de cercetare mai amanuntit
Detaliaza din planul de studiu
Cum vor fi selectati subiectii si lotul martor Cum vor fi masurate variabilele
Probleme si solutii: exemple

Ce relatie exista intre depresie si sanatate? Consumul de carne rosie determina cancer?
Scaderea colesterolului seric previne boala

cadiaca ischemica?
Anatomia Cercetarii Clinice
Fiziologia cercetarii clinice:

Cum are loc?
Se folosesc masuratorile intr-o proba / esantion /lot de studiu pentru a extrage inferente despre fenomene (variabile) intr-o populatie
Tipuri de variabile
Variabile de confuzie*
Predictor*
Rezultat
Modificatori ai efectului*
*Considerate general ca expunere la factori de risc
Problema de studiu
In studii descriptive: Intr-o populatie de [study population], care este prevalenta [outcome variable]?
In studii analitice :
Intr-o populatie de [study population], este [predictor variable] asociata cu [outcome variable]?
Tipuri de studii clinice

Studii fara variabile
Studii de caz, serii de cazuri, editoriale, opinii / comentarii, rapoarte review
Studii cu o singura variabila

Studii descriptive
Studii cu 2 variabile
Experimente Studii observationale Meta-analize si review-uri sistematice
Ierarhia tipurilor de studii clinice
Descriptive studies Experimental studies
Analytic studies Observational studies
Cohort
Case-control
Cross-sectional
Conceptie (study design) legata de obiectivele studiului.

Conceptie inainte de colectarea si analiza datelor Concepta studiului este importanta intrucat permite o crestere a validitatii si reducerea erorilor.
Variabile
Variabila predictor (independenta)
Variabila rezultat (dependenta)
Factori care influenteaza conceptia studiului
1. Obiectivele studiului intrebarile cercetarii

2. Epidemiologia bolii / expunerii - rara / comuna
3. Aspecte etice
4. Resurse- bani, oameni, infrastructura
Ce tip de studiu este mai adecvat?

Telefonia mobila determina cancer cerebral? Dieta afecteaza riscul de cancer mamar? Fumatul pasiv determina cancer pulmonar?
Tipuri de study design

1. Experimental/ Quasi-experimental sau observational
2. Directia studiului in relatie cu expunerea si aparitia bolii 3. Cantitativ /Calitativ
Women's Health Initiative (1991) http://www.nhlbi.nih.gov/whi/

Ar trebui sa primeasca substitutie cu estrogeni femeile postmenopauza?
Women's Health Initiative (1991)

Ar trebui sa primeasca substitutie cu estrogeni femeile postmenopauza?
Subiecti: femei postmenopauza Predictor: estrogeni Rezultat: ?
Ameliorarea problemei de cercetare

Tratamentul cu estrogeni previne accidentul coronarian la femei postmenopauza?
Subiecti:femei postmenopauza Predictor: tratament cu estrogeni vs no treat Rezultat: accident coronarian
FINER?
Fezabil Interesant Nou Etic Relevant
Sapte tipuri de studii

1. Randomized controlled trial 2. Cohort study 3. Case-control study 4. Sample survey or cross sectional study 5. Ecologic or trend study 6. Case report or series 7. Qualitative research
Ncesitatea desing-ului
Trial clinic randomizat
Puncte finale Interes primar
Studiu observational
Cross-sectional Caz control Cohorta
1. Studii Experimental / Interventionale Randomized controlled trial (RCT)

Evaluarea de noi metode de profilaxie si tratament Medicamente si terapii noi pentru boli Tehnologii medicale si tehnici de ingrijire noi Metode noi de preventie primara Programe noi de screening si detectare precoce Sisteme noi de asistenta sanitara comunitara (community trial ) Impactul noilor politici in sistemul de sanatate si finantarea sistemului sanitar ( community trial )
Randomized controlled trial

Cel mai bun design- randomizare, eroare de selectie minima
(dar nu zero); Nu este etic: daca interventie poate dauna, rezultat clinic slab
Nu este practic boli rare, efect rar;

Participarea subiectilor la studiu este cruciala.
Randomized Controlled Trial

Elemente
Selectia subiectilor
- trasaturi similare - criterii includere /excludere
Design
Definirea populatiei
Randomizare
Alocarea subiectilor
Interventie
Tratament nou
Tratament curent /no treatment
Outcome Colectarea datelor
Ameliorat
Ne ameliorat
Ameliorat
Ne ameliorat
Masking (blinding)
Randomized Controlled Trial

Blinding
Double- subjects & investigators Single subjects (placebo effect) Triple blind- subjects & investigators & statisticians
Outcome / endpoint
improvement ( desired effect) and side effects must be explicitly defined
measured comparably in all study groups
Multi-centre trial Comply with GCP requirements Clinical trials/ community trials
Results of RCT- benchmark- good clinical practice (GCP) , clinical governance, treatment protocol.
Superiority or equivalence trials Parallel - most common
Types of RCT:
A B
Cross over
- Planned washout period
randomized
- Unplanned
A B
randomized
B A
Medical
Require surgery No surgery
Surgical
Refuse surgery Surgery
Analyze outcome by intention to Rx
Limite
1. ? Eficienta n comunitati necontrolate 2. Refuzul consimmntului informat - selectare automat (persoane care particip sunt diferite de cele care nu o fac) 3. Necomplianta (persoanele compliante sunt foarte diferite de cele care nu sunt) - Drop-out: nu adera la regim experimental, pierderea din studiu - Drop-in: nu adera la regimul de control 4. Complianta- necesita monitorizare 5. Cele mai costisitoare tipuri de studii
Studii observationale
1. Cohort study 2. Case-control study 3. Cross sectional study 4. Ecologic or trend study 5. Case report or series 6. Qualitative research
Direction, timing , +/- control
Studiu de cohorta
Subiecti
5000 femei cu varsta 55+ ani
Factor predictor:
estrogeni post-menopausal?
Outcome:
Incidenta accidentelor coronariene dupa 5 ani de terapie
Cand este bun un studiu de cohorta?

Atunci cnd exist dovezi bune pentru asocierea bolii, cu o anumit expunere
Atunci cnd expunerea este rar i incidena bolii in randul celor expusi este frecvent Cnd intervalul de timp dintre expunere si boala este scurt
Atunci cnd cercettorul are o speran de via lung!
Cohorta
Cohorta: "orice grup desemnat de persoane care sunt urmrite pe o perioad de timp
Cazurile selectate in cohorta trebuie sa fie fara boala cercetata la nceputul urmaririi (populaia la risc) De obicei cohorta este definita sau submprita n funcie de statutul de expunere
Populatia la risc
All subjects within a cohort must be free of the outcome at the start of the follow-up period
All subjects must be at risk for developing the disease (population at risk)
Studii de cohorta Prospective vs. Retrospective

Prospective
Control mai bun al calitii i cantitii de date Potenial mai mic de bias Mai consumatoare de timp Mai scumpe
Retrospective
Control mai slab al calitii i cantitii de date Potenial mai mare de eroare Mai rapide Mai ieftine
Pierderea din urmarire (Loss to Follow-up)

Problem, mai ales dac subiecii pierduti sunt la risc mai mare / mai mic de a dezvolta boala comparativ cu alti subiecti Chiar mai ru dac lost to FU apare diferit in subgrupuri Un nivel <60% de urmarire in cohorta este, n general, privit cu scepticism
Analiza datelor studii de cohorta
Start with exposure, then follow to see whether Incidence rate total Disease + Disease of disease Exposed + a b a+b
a/a+b
Exposed -
c+d
c/c+d
Analiza datelor studii de cohorta
Riscul absolut = incidena cazurilor de boal n lotul expus / populaia total Riscului relativ =
Incidenta bolii la E+ Incidenta bolii la E-
Taria asociatiei (Odds Ratio) = ad / bc
Limite
Unele expuneri la risc se pot modifica n timp ex mbtrnire, stilul de via (diet, fumat), expunerea la produse farmaceutice, poluarea aerului Modificri privind metoda de-a lungul timpului, identificarea bolii Prospectiv - follow-up, deci cu perioade lungi Costisitor Potential de eroare: eroare de selecie (care subiect a fost expus i care nu) eroare de anamneza - date istorice eroare n evaluarea rezultatelor eroare prin lipsa de rspuns i pierdere la f / u eroare analitic
Cross-sectional design
Subiecti
2000 femei varsta 55+ ani
Predictor:
Tratament post-menopausal cu estrogeni?
Rezultat:
Istoric de accident coronarian?
Sample survey or cross sectional study :

It is a survey of the frequency of disease and other characteristics in a defined population at one particular time. Focus on describing a state or process at a fixed time.
Suitable for describing prevalence and distribution of heath problem in a community. (prevalence or health survey).
Sample survey or cross sectional study : cont
In clinical research, used in :

Describing disease presentation (spectral description study) Diagnostic test accuracy study Quality of care assessment.
Generally efficient but large scale community survey can be expensive. Sometimes survey data given causal interpretation (pseudo-longitudinal) but liable to error, caution.
Advantages of Cross Sectional Study Design

One stop shopping Less expensive Potentially can detect effect of exposure that do not vary over time
Disadvantages of Cross Sectional Study Design

May not detect associations that for diseases with short duration that have cyclic or seasonal trends (e.g. some infectious diseases)
May require over-sampling of low prevalence exposure or disease groups
Design Case-control
Subiecti / femei la menopauza
Cazuri: 100 femei cu accident coronarian Controale: 100 femei fara patologie cardiaca
Predictor:
Au luat estrogeni post-menopauza?
Rezultate:
Cazuri vs controale
Controls
Case Control Studies compare exposure history of cases and controls Controls provide exposure distribution of exposure (exposed and unexposed cohorts) in source population that gave rise to the cases in the study Biggest Problem: Identifying an appropriate control group
Sources for Controls

Population Controls Neighborhood Controls
Random-Digit Dialing
Hospital-Based Controls
Nested Case Control Studies

Every Case Control Study can be thought as being conducted within a cohort study
Cases represent the outcomes of the cohort Controls provide estimate of exposure distribution of cohort
Traditionally, Nested Case Control Study usually refers to study that are conducted within the experience of a well-defined cohort study
Comparison of Case Control and Cohort Studies

Primary Difference:
Cohort Study involved complete enumeration of the source population Case Control Study involved a sample (controls) of the source population
Case Control Studies are modified Cohort Studies
When is a case control study warranted?

When there is good evidence of an association between a certain exposure and the disease
When disease is rare and exposure is frequent among exposed Advantage:
Cost- relatively inexpensive Sample size relatively small
Analysis of data -case control study

Begin with cases with disease and controls without
disease, then measure past exposure Disease + Disease total
Exposed + Exposed Proportion of exposed
a
c a/a+c
b
d b/b+d
a+b
c+d
Odd ratio= a/a+c / b/b+d= ad/bc
Etic?
Echivalenta (nu este sigur daca domina beneficii sau riscuri) Beneficii ale terapiei de substitutie Scad simpotomele de climax ? Preventia fracturilor ? Preventia BCI ? Preventia Alzheimer ? Cresterea calitatii vietii
Riscuri ? trombo-embolism pulmonar ? Cancer mamar
Relevant?
Estrogeni / estroprogestative Decizia afecteaza o mare parte din populatie
TRECUT
A primit HRT?
PREZENT
Cancer mamar
No
Yes Cazuri
No
Yes Controale
Fara cancer de san
Case report or series :

Description of one or several cases in which no attempt is made to answer specific hypotheses or to compare results with another group of cases.
classical clinical study; its value probably under rated
Case report or series

Description of one or several cases in which no attempt is made to answer specific hypotheses or to compare results with another group of cases No control
Classical clinical study Its value probably under rated
Case Reports and Case Series

Example: investigators at a single institution note that a small number of patients treated with a alternative (complementary) therapy exhibit longer survival and better survival than "expected" Example: investigators notice a higher than expected incidence of a cancer in a community Example: investigators note a common occupational exposure in a series of patients with a rare cancer
Case Reports and Case Series

Problems: lack of a control group
no measure of effect no formal statistical analysis
Advantages: hypotheses generators
Case Series With Literature Controls

Compare outcomes of case series to "expected" results based on existing records (e.g. published results, national incidence/mortality rates) Problems: lack of comparability
Confounding
Healthy Worker Effect
Bias
5. Ecologic or trend study :

Group based study Unit of observation is a group eg country, state etc.
Observed effect difficult to interpret at individual level (ecologic fallacy).
Otherwise efficient to do.
5. Ecologic or trend study :

Group based study, unit of observation is a group e.g. country, state etc. Ignore variability between individuals May ascribe to members characteristics they do not possess as individuals
Age standardized death rate per 1000 Quantity of salt sold at Henan province in China
Qualitative research :
Development of concepts which help us to understand social phenomena in natural settings, giving due emphasis to the meanings, experiences, and views of all the participants It does not primarily seek to provide quantified answers to research questions Particularly useful for explaining complex phenomena not amenable to quantitative research
Conceptia unui plan de cercetare

1. Definitia problemei
2. Dezvoltarea planului de cercetare

Lista elementelor studiului Identificarea referintelor publicate
3. Introducerea (fondul problemei) si semnificatia sa (istoric al cercetarilor anterioare, motivatie, importanta)
Plan de studiu
Problema cercetata Semnificatie (background) Designul studiului Populatia de studiu si esantionarea Variabile si masuratori Elemente statistice
Problema principala a studiului? De ce este important? Cum se va face studiul ?
Care sunt subiectii si cum sunt selectati? Ce masuri vor fi luate? Dimensiunea lotului si analiza? Aspecte etice Exista probleme etice? Controlul calitatii si evaluarea Cum se asigura controlul calitatii datelor datelor si analizei acestora?
Fond si semnificatie
Bazat pe experienta
Atentie la idei noi

Atentie la tehnologii noi Sa fim constienti despre punctele forte si slabe ale cercetarilor anterioare similare, proprii sau de literatura Sa stim ce dorim sa comunicam / confirmam la final
Fondul si semnificatia problemei / importanta pentru protocol

Asemanator cu introducerea la un articol Introduce cercetarea propusa, in context Descrie motivatia studiului Ce se stie despre topic De ce este problema propusa, importanta? Ce tip de raspuns asteptam de la studiu?
Fond si semnificatie
Citarea cercetarilor relevante anterioare (inclusiv propriile date)
Indica punctele forte si slabe ale studiilor anterioare, ca si intrebarile ramase fara raspuns. Arata cum vor fi folosite rezultatele studiului propus pentru rezolvarea neclaritatilor si influentarea politicii de sanatate sau practicii clinice
Gasirea literaturii adecvate

End note, Reference manager Verifica formatul referintelor conform instructiunilor pentru autori si sunt incluse pe masura ce se scrie protocolul Se pastreaza copii ale tuturor referintelor PubMed: www.ncbi.nlm.nih.gov Comunicari personale (cine si cand) Date nepublicate (Cel mai bine se evita)
Gasirea literaturii adecvate

End note, Reference manager Verifica formatul referintelor conform instructiunilor pentru autori si sunt incluse pe masura ce se scrie protocolul Se pastreaza copii ale tuturor referintelor PubMed: www.ncbi.nlm.nih.gov Comunicari personale (cine si cand) Date nepublicate (Cel mai bine se evita)
Colectarea datelor Strategii de masurare
Corin Badiu, 2007
Obiective
Stabilirea tipurilor de variabile
Surse IT de date Identifica si localizeaza seturile corecte de date
In institutie In afara institutiei
Strategii de masurare
Analiza, interpretarea si raportarea rezultatelor
Selecteaza programul adecvat: Excel, SPSS Foloseste programele pentru analize statistice simple si prezentarea grafica a rezultatelor Interpreteazarezultatele
Tipuri de variabile
Variabile de confuzie*
Predictor*
Rezultat
Modificatori ai efectului*
*Considerate general ca expunere la factori de risc
Tipuri de studii clinice

Studii fara variabile
Studii de caz, serii de cazuri, editoriale, opinii / comentarii, rapoarte review
Studii cu o singura variabila

Studii descriptive
Studii cu 2 variabile
Experimente Studii observationale Meta-analize si review-uri sistematice
Ierarhia tipurilor de studii clinice
Studii clinice
Descriptive Experimentale Cohorta
Analitice Observationale Caz-control Cross-sectional
Variabile
Variabila predictor (independenta)
Variabila rezultat (dependenta)
Evidence Based Medicine

Metode de tratament sustinute de dovezi clinice si de cercetare. Necesita integrarea celor mai bune dovezi din cercetare pentru diagnostic si tratament cu experienta clinica. Ia in considerare ce este optim pentru fiecare pacient precum si preferintele acestuia.
Realitatea
Cercetarea asupra eficientei de tratament face subiectul unui numar mic de articole. Evidence based medicine este considerat un concept ce foloseste baze de date inclusiv studii sistematice de caz pentru a ghida interventii terapeutice. Dovezile trebuie evaluate intr-un context terapeutic efectiv, Ce tip de interventie capata sens pentru mine ca practician?
Clinical Questions
What is the best choice of therapy for my patient? Is this program theoretically sound? Does this therapy program work? How long with the therapy take? Where do I go from here?
Practicing Clinicians Needed!

Clinicians are on the front line have necessary clinical expertise know their patients well are naturally scientific thinkers are well-versed in data collection know how to look for outcomes
Baseline Measurements
A baseline is a measure of response rates in the absence of treatment Baselines Establish a need for treatment Document improvement Allow us to modify if we dont see improvement
Baseline Data
Create a set of exemplars of each of your targets and prepare a recording sheet. Utilize criterion referenced measures.
Data Collection Strategies
Always have more than one measurement Check the reliability of the baseline data Select research/clinical design
Research/Clinical Designs
ABA designs Test, treat and test ABAB designs Test, treat, test and treat Time-Series designs Establish stable baseline Begin treatment Measure treatment results Multiple-Baseline designs Have a number of different baselines Each baseline must be independent of the others Only treat one variable
Data Collection Instruments

Requirements
Reliable Valid Responsive Universal Unbiased
Data Collection Instrument

Is it reliable?
Will the instrument measure consistently across: Different testing situations?
Test-retest reliability
Different judges?
Inter-rater reliability

Is it valid?
Is the instrument being used to measure the kind of data for which it was intended?

Is it responsive?
The instrument should be equally sensitive, whether a characteristic is present or absent.
Must measure both: False-negatives: You thought it was intact, but it was torn. False-positives: You thought it was torn, but it was intact.

Is it universal?
The investigator should employ a widely used data collection instrument, which helps minimize reporting bias because the data can then be compared with other published literature.

Is it unbiased?
There should be no difference between the true value and the value that an investigator actually obtains other than a difference caused by sampling variability.
Sampling Methods
Random Sampling (Simple)

Systematic Sampling
Stratified Sampling
4. Cluster Sampling
5. Convenience Sampling
6. More complex sampling
Qualitative and Quantitative Variables

Examples of qualitative variables are occupation, sex, marital status, and etc
Variables that yield observations that can be measured are considered to be quantitative variables. Examples of quantitative variables are weight, height, and age Quantitative variables can further be classified as discrete or continuous
Variables types
1. Categorical variables (e.g., Sex, Marital Status, income category) 2. Continuous variables (e.g., Age, income, weight, height, time to achieve an outcome) 3. Discrete variables (e.g.,Number of Children in a family) 4. Binary or Dichotomous variables (e.g., response to all Yes or No type of questions)
Scale of Data
1. Nominal: These data do not represent an amount or quantity (e.g., Marital Status, Sex)
2. Ordinal: These data represent an ordered series of relationship (e.g., level of education) 3. Interval: These data is measured on an interval scale having equal units but an arbitrary zero point. (e.g.: Temperature in Fahrenheit) 4. Interval Ratio: Variable such as weight for which we can compare meaningfully one weight versus another (say, 100 Kg is twice 50 Kg)
Variables in the protocol

TYPES OF VARIABLE
independent dependent intermediate confounding
Independent Variable
The characteristic being observed and/or measured that is hypothesized to influence an event or outcome (dependent variable). NOTE The independent variable is not influenced by the event or outcome, but may cause it or contribute to its variation.
Dependent Variable
A variable whose value is dependent on the effect of other variables (ie., independent variables) in the relationship being studied. Synonyms: outcome or response variable. NOTE an event or outcome whose variation we seek to explain or account for by the influence of independent variables.
Intermediate Variable
A variable that occurs in a causal pathway from an independent to a dependent variable. Synonyms: intervening, mediating NOTES it produces variation in the dependent variable, and is caused to vary by the independent variable. such a variable is associated with both the dependent and independent variables.
Confounding Variable
A factor (that is itself a determinant of the outcome), that distorts the apparent effect of a study variable on the outcome. NOTE such a factor may be unequally distributed among the exposed and the unexposed, and thereby influence the apparent magnitude and even the direction of the effect.
Organizing Data
1. 2. 3. 4. 5. 6. 7. 8. 9. Frequency Table Frequency Histogram Relative Frequency Histogram Frequency polygon Relative Frequency polygon Bar chart Pie chart stem-and-leaf display Box Plot
Frequency Table
Suppose we are interested in studying the number of children in the families living in a community. The following data has been collected based on a random sample of n = 30 families from the community. 2, 2, 5, 3, 0, 1, 3, 2, 3, 4, 1, 3, 4, 5, 7, 3, 2, 4, 1, 0, 5, 8, 6, 5, 4 , 2, 4, 4, 7, 6 Organize this data in a Frequency Table!
Frequency Table
X=No. of Children Count (Freq.)
0 1 2 3 2 3 5 5
Relative Freq.
2/30=0.067 3/30=0.100 5/30=0.167 5/30=0.167
4
5 6 7 8
6
4 2 2 1
6/30=0.200
4/30=0.133 2/30=0.067 2/30=0.067 1/30=0.033
Frequency plot
6 5 4 3 2 1 0 0 1 2 3 4 5 6 7 8 Freq.
Frequency Table
Now suppose we need to construct a similar frequency table for the age of patients with Heart related problems in a clinic. The following data has been collected based on a random sample of n = 30 patients who went to the emergency room of the clinic for Heart related problems. The measurements are: 42, 38, 51, 53, 40, 68, 62, 36, 32, 45, 51, 67, 53, 59, 47, 63, 52, 64, 61, 43, 56, 58, 66, 54, 56, 52, 40, 55, 72, 69.
Frequency Table
Age Groups Frequency Relative Frequency
2/30=0.067
32 -36.99
37- 41.99
42-46.99 47-51.99 52-56.99 57-61.99 62-66.99 67-72 Total
3
4 3 8 3 4 3 n=30
3/30=0.100
4/30=0.134 3/30=0.100 8/30=0.267 3/30=0.100 4/30=0.134 3/30=0.100 1.00
Measures of Central Tendency

Where is the heart of distribution? 1. Mean 2. Median 3. Mode
Empirical Rule
For a Normal distribution approximately,
a) 68% of the measurements fall within one standard deviation around the mean
b) 95% of the measurements fall within two standard deviations around the mean c) 99.7% of the measurements fall within three standard deviations around the mean
Prerequisite Skills
Fundamental concepts of measurement
Scales of measurement Distribution, central tendency, variability, probability Disease prevalence and incidence Disease outcomes (eg, fatality rates) Associations (correlation or covariance) Health impact (eg, risk differences and ratios) Sensitivity, specificity, predictive values
Scales of Measure
Nominal qualitative classification of equal value: gender, race, color, city Ordinal - qualitative classification which can be rank ordered: socioeconomic status of families Interval - Numerical or quantitative data: can be rank ordered and sizes compared : temperature Ratio - interval data with absolute zero value: time or space
Distribution, Central Tendency

Mean
Variability, Probability
Mean Median Mode Standard deviation Statistical Significance p < .01
Confidence Interval
Statistical Significance Type I and Type II errors

Null Hypothesis = Ho Ho True Reject Ho Type I error Ho False Correct decision
Do Not Reject Ho
Correct decision
Type II error
Statistics Online Textbook

The Statistics Homepage http://www.statsoftinc.com/textbook/statho me.html
Disease Prevalence and Incidence

Prevalence
probability of disease in entire population at any point in time 2% of the population has diabetes
Incidence
probability that patient without disease develops disease during interval 0.2% or 2 per 1000 new cases per year
Sensitivity, Specificity
sensitivity = a / (a+c) specificity = d / (b+d)
Patients with disease Test is positive Test is negative Patients without disease
Predictive Value
Positive predictive value = a / ( a+b) Negative predictive value = d / (c+d) Post-test probability of disease given positive test = a / (a+b) Post-test probability of disease given negative test = c / (c+d)
Patients with disease Test is positive

Test is negative
Patients without disease
a
c
b
d
Good Resource Sen, Spc, PV

An Introduction to Information Mastery http://www.poems.msu.edu/InfoMastery/de fault.htm
Diagnosis
Sensitivity and specificity Predictive values Likelihood ratios
InfoRetriever
Calculators: Epidemiology, Diagnostic test
Bias in Clinical Trials

Areas in which bias can occur
Systematic error in . . . Allocation Response Assessment

Allocation or Susceptibility Bias
Can occur when patient assignments to a trial group are influenced by an investigators knowledge of the treatment to be received.
Can result in treatment groups that have different prognoses.

Allocation or Susceptibility Bias
Treatment groups must have similar prognoses, which is achieved by:
Randomization of patients Prospective evaluation of patients Well-defined inclusion and exclusion criteria
Randomization in Clinical Trials

Occurs when patients are assigned to treatments by means of a mechanism that prevents both the patients and the investigator from knowing which treatment is being assigned.
Benefits of Randomization
Prevents the systematic introduction of bias. Minimizes the possibility of allocation bias. Balances prognostic factors for treatment groups.
Improves the validity of statistical tests used to

compare treatments.

Response & Assessment/Recording Bias
Can occur when a patient reports a treatment response or when an investigator assesses that responseeither person can be influenced by knowing the treatment. A patient or an investigator may have a preconceived idea of which treatment is better. The patient may also want to please the investigator.

Blinding
To minimize Response & Assessment/Recording Bias
Single Blind (patient blinded): protects against response bias.

Double Blind (patient and investigator blinded): protects against assessment/recording bias as well as response bias.

Transfer bias Occurs when patients are lost to follow-up. Must be minimized. Performance bias Can occur with a single surgeon or with multiple surgeons.
Confounding Example
Relationship between coffee and pancreatic cancer, BUT Smoking is a known risk factor for pancreatic cancer Smoking is associated with coffee drinking but it is not a result of coffee drinking.
What is confounding?
If an association is observed between coffee drinking and pancreatic cancer
Coffee actually causes pancreatic cancer, or The coffee drinking and pancreatic cancer association is the result of confounding by cigarette smoking.
How to handle confounding

If you know something is a possible confounder, in the data analysis use
Stratification, or Adjustment
Fear the unknown!
Study Design Taxonomy

Treatment vs. Observational Prospective vs. Retrospective Longitudinal vs. Cross-sectional Randomized vs. Non-Randomized Blinded/Masked or Not
Single-blind, Double blind, Unblinded
Randomization: Definition
Random Allocation
known chance receiving a treatment cannot predict the treatment to be given
Eliminate Selection Bias Similar Treatment Groups
ONE Factor is Different

Randomization tries to ensure that ONE factor is different between two or more groups. Observe the Consequences Attribute Causality
Types of Randomization
Standard ways: Random number tables (see text) Computer programs NOT legitimate Birth date Last digit of the medical record number Odd/even room number
Types of Randomization
Simple Blocked Randomization Stratified Randomization
Simple Randomization
Randomize each patient to a treatment with a known probability
Corresponds to flipping a coin
Could have imbalance in # / group or trends in group assignment Could have different distributions of a trait like gender in the two arms
Block Randomization
Insure the # of patients assigned to each treatment is not far out of balance Variable block size
An additional layer of blindness
Different distributions of a trait like gender in the two arms possible
Stratified Randomization
A priori certain factors likely important (e.g. Age, Gender) Randomize so different levels of the factor are balanced between treatment groups Cannot evaluate the stratification variable
Stratified Randomization
For each subgroup or strata perform a separate block randomization Common strata
Clinical center, Age, Gender
Stratification MUST be taken into account in the data analysis!
Outline
Introductory Statistical Definitions What is Randomization? Randomized Study Design Experimental vs. Observational Non-Randomized Study Design Stat Software, Books, Articles
Types of Randomized Studies

Parallel Group Sequential Trials Group Sequential trials Cross-over Factorial Designs
Parallel Group
Randomize patients to one of k treatments Response
Measure at end of study Delta or % change from baseline Repeated measures Function of multiple measures
Ideal Study - Gold Standard

Double blind Randomized Parallel groups
Two Scenarios
Study 1
A U.S. study (2000) compared 469 patients with brain cancer to 422 patients who did not have brain cancer. The patients cell phone use was measured using a questionnaire. The two groups use of cell phones was similar.
Study 2
An Australian study (1997) conducted a study with 200 transgenic mice. One hundred were exposed for two 30 minute periods a day to the same kind of microwaves with roughly the same power as the kind transmitted from a cell phone. The other 100 mice were not exposed. After 18 months, the brain tumor rate for the exposed mice was twice as high as that for the unexposed mice.
Example taken from Statistics: The Art and Science of Learning
206
Questions to Consider
How do the two studies differ?
Study 1
Study 2
Why do the results of different medical studies sometimes disagree?
Could the second study be performed on human beings?
Suppose a friend recently diagnosed with brain cancer was a frequent cell phone user. Is this strong evidence that frequent cell phone use increases the likelihood of getting brain cancer?
Informal observations of this type are called _____________ _____________. You should rely on reputable research studies, not anecdotes.
Two Main Ways to Gather Data

Observational Study
The researcher observes values of the response and explanatory variables for the sampled subjects without imposing any treatments Example:
Experiment
The researcher assigns experimental conditions (also called treatments) to subjects (also called experimental units) and then observes outcomes on the response variable. Treatments correspond to values of the explanatory variable Example:
Types of Observational Studies

Retrospective
Observational studies that look back in time
This is sometimes done to find risk factors for certain diseases
Cross-Sectional
Observational studies that take a cross section of the population at the current time
Prospective
Observational studies in which subjects are followed into the future
Advantages of Experiments over Observational Studies

In an observational study, there can always be lurking variables affecting the results. This means that observational studies can _________ show causation. It is easier to adjust for lurking variables in an experiment. In general, we can study the effect of an explanatory variable on a response variable more accurately with an experiment than with an observational study.
Disadvantages of Experiments
They can be ____________ to perform on the subjects in which you are interested. It can be difficult to monitor subjects to ensure that they are doing what they are told. They can take many years, even decades, to complete. Results of experiments that use animals do not ______________ to humans. They are unnecessary the question of interest does not involve trying to assess _____________.
Sampling Designs for Observational Studies

Simple Random Sampling (SRS)
A simple random sample of n subjects from a population is one in which each possible sample of that size has the _______ chance of being selected.

Stratified Sampling
A stratified random sample divides the population into separate groups, called ________, and then selects an SRS from each stratum.

Cluster Sampling
A cluster random sample can be used if the target population naturally divides into groups, each of which is representative of the entire target population. In this method, a SRS of groups (or strata) is taken. Every member of the selected groups is put into the sample.

Systematic Sampling
A systematic sample selects every kth person from the sample frame. The researcher randomly selects a number between 1 and k in order to know which person to select first, then selects every kth person after this.
Advantages of the Various Sampling Designs

Simple Random Sampling (SRS)
It is the easiest most widespread form of sampling. Each subject has an _______ chance to be in the sample. The sample enables us to determine how likely it is that descriptive statistics (like the sample mean) fall close to corresponding values for which we would like to make inference (like the population mean).
Advantages of the Various Sampling Designs

Stratified Sampling
It ensures that there are enough _________ in each group that you want to compare.
Cluster Sampling
It does not require a sampling frame of subjects. It is less ___________ to implement.
Bias in Sampling
A sampling method is _________ if
The sample tends to favor some parts of the population over others. In other words, the results from the sample are not representative of the population.
Obviously, __________ samples are our goal.
Types of Bias
Undercoverage
Occurs when a sampling frame leaves out some groups in the population
Nonresponse bias
Occurs when some sampled subjects cannot be reached, refuse to participate or fail to answer some questions
Response bias
Occurs when the subject gives an incorrect response or when the question wording or the way the interviewer asks the questions is confusing or misleading
Examples of Poor Samples that Result in Bias

Convenience Samples
Voluntary Response Samples
Elements of a Good Experiment

Control group
Gives us something to compare against Enables us to control the __________ _______
The placebo effect occurs when patients seem to improve regardless of the treatment they receive.
Randomization
Eliminates ______ that can result when researchers assign treatments to the subjects Balances the group on variables that you know affect the response Balances the group on _________ variables that may be unknown to you
Elements of a Good Experiment

Blinding
Increases reliability of the results
_________-blind: subjects do not know the treatment assignment _________-blind: neither the subjects nor those in contact with the subjects know the treatment assignment
Example
A pharmaceutical company has developed a new drug for treating high blood pressure. To determine the effectiveness of the drug, the company conducted an experiment in which subjects with a history of high blood pressure were treated with the new drug. A later experiment randomly divided subjects with a history of high blood pressure into two groups. Group A was treated with the new drug as before. Group B received the most popular drug on the market at that time. The subjects were unaware of which treatment they received. 60% of the patients in Group A improved, while 63% of the patients in Group B improved. The __________ experiment is better because
Example
To investigate whether antidepressants help smokers to quit smoking, one study used 429 men and women who were 18 or older and had smoked 15 cigarettes or more per day in the previous year. They were all highly motivated to quit and in good health. They were assigned to one of two groups: one group took an antidepressant called Zyban, while the other group did not take anything. At the end of a year, the study observed whether each subject had successfully abstained from smoking.
Example taken from Statistics: The Art and Science of Learning
226
Logic Behind Randomized Comparative Experiments

Randomization ensures that the groups of subjects are similar in all respects before the treatments are applied. Using a control group for comparison ensures that external influences operate equally on both groups. If the groups are large enough, natural differences in subjects will average out. This means that there be little difference in the results for the groups unless the treatments themselves actually cause the difference.
Did You Know?

Observational studies can also have control groups.
These are called ______-________ studies. The cases are people who have a certain disease or condition, and the controls are people who do not have the disease. Their purpose is to see if one of the explanatory variables is related to the disease. _________ from the beginning of these notes is an example of a case-control study.
Important Points
Types of studies: Observational studies and experiments Experiments control for lurking variables Sampling designs: SRS, stratified random samples and cluster samples SRS is the preferred method Potential sources of bias: Undercoverage Response bias Nonresponse bias Convenience sampling Voluntary response sampling Elements of good experiments: Control group, randomization and blinding
Important Points
If a group is underrepresented in the sample, we cannot make inference about it. We must be careful when interpreting the results of observational studies. For comparison of several treatments to be valid, you must apply all treatments to similar groups of experimental units. Interesting questions are usually pretty tough to answer. This is due in part to the fact that no single experiment or observational study can determine causation.
Stop and Think!!!

Write the study! Describe & classify the variables. Instruments for measure? Bias?
Prepare to analyze data!
Consimtamantul informat in cercetarea tiinific
Corin Badiu, 2007
Etica Definitii academice si practice

Ramura a disciplinelor filozofice, considerata stiinta de normare intrucat se ocupa de normele conduitei umane. [academic]
Procesul prin care se aplica valorile morale la situatii actuale de viata. [practic]
Aspecte istorice si religioase

Etica: un corp de norme si standarde de conduita umana care guverneaza comporetamentul indivizilor si grupurilor. [istoric]
Etica: disciplina de viata rezultata din aplicarea normelor si preceptelor religioase [Religie]
Individ si Grupuri
Etica: domeniu de studiu care ajuta individul pentru aplicarea propriilor valori si principii pentru a le conduce comportamentul. [individual] Etica: un set de reguli pe care le studiem si aplicam pentru a duce la indeplinire misiunea unei organizatii / institutii. [group]
Etica instututionala
Institutie = grup:
Actioneaza colectiv pentru indeplinirea scopurilor institutionale
Institutie = individ:
Foloseste valori comune cu etica individuala pentru a lua decizii
Atat institutiile cat si indivizii:

Norme de etica
Protocolul de evaluare etica in cercetare
1. Fond, Scopuri, Obiective

2. Metodologia cercetarii 3. Participanti 4. Recrutare 5. Riscuri si Beneficii 6. Confidentialitate 7. Compensare
8. Conflict de Interese
9. Elaborarea si aplicarea consimtamantului Informat 10. Evaluarea prin comitete si institutii 11. Contract 12. Trialuri Clinice
13. Anexe
Fond, Scopuri, Obiective
Care este subiectul cercetarii?

Ce scopuri se vor indeplini prin cercetare? Care sunt principalele intrebari la care se doreste raspuns? Descrie pe scurt fondul stiintific al studiului pagina
Metodologia cercetarii
Secventa logica de evenimente din cadrul studiului (protocol) Cum se vor obtine datele? Descriere detaliata pentru fiecare metoda. Pune urmatoarele intrebari:
Cat dureaza interviul/chestionarul/observatia experimentala? Cand (in ce perioada) va avea loc? Unde va avea loc? Participantii vor avea posibilitatea sa intervina in chestionar/studiu? Daca da, ofera detalii.
Care sunt implicatiile /aplicatiile cercetarii?
Principii ale eticii in cercetare

Onestitate Obiectivitate Integritate (cine esti, ce faci, ce spui) Utilizarea eficienta a resurselor (timp, materiale, echipamente, personal) Colegialitate (utilizare in comun) Recunoasterea autoritatii (ca authorship si mentor) Deschidere (dezvaluirea detaliilor)
Practica responsabilitatii cercetarii

Ce inseamna?
Urmarirea si aplicarea unui protocol scris Verificarea si documentarea datelor (inclusiv lotul de reactivi, date de exp., etc.) Pastrarea adecvata a rezultatelor si specimenelor Pastrarea adecvata a reactivilor si chimicalelor Mentinerea si calibrarea adecvata a echipamentelor Utilizarea Standardelor Procedurilor de Operare (SOP) Grija pentru animalele de experienta
Participanti
Cine sunt participantii? Organizatii? Indivizi? De ce au fost alesi pentru studiu? (criterii de excludere / includere) Cati sunt? Argumenteaza dimensiunea esantionului
Recrutare
Cum veti obtine o lista a potentialilor participanti? Sistem de contact telefonic Email scrisoare ?
Grupuri de studiu: Control, Test
Riscuri si Beneficii
Standarde de aplicare:
Nu exista risc minim anticipat. Participantii vor fi informati despre natura studiului si modalitatii de participare, inclusiv asupra faptului ca se pot retrage oricand. Participantii (si raspunsurile lor privind includerea in studiu) vor fi luate ca atare
Confidentialitate
Cine va avea acces la date?

Se va inregistra interviul? Cum va fi protejata identitatea participantilor? Se codifica toate datele? Cum se stocheaza datele in timpul studiului? Cand se distrug datele? Cum se va pastra confidentalitatea ? Se va exclude orice informatie de identificare?
Procesul de consimtamant informat

Fundamental in cercetarea pe subiecti umani
Este un proces si nu un formular. Formularul este doar documentul care atesta ca procesul de informare liber consimtita a avut loc.
Se va obtine consimtamant informat scris?

De la nivel institutional? De la decan/ rector?
Consimtamantul informat trebuie obtinut de la toti participantii

Interviu consimtamant scris Chestionare Prin completarea chestionarelor
Pentru studii avand ca subiecti copii, consimtamantul scris al parintilor / tutorilor este obligatoriu
Cum obtinem CI?

Variaza in functie de designul studiului si natura participarii Verbal vs. Scris
Investigator vs. Co-investigatori / asistenti
Anexe
Text Telefonic / email

Exemple de scrisori de consimtamant Ghiduri de Observatie clinica Chestionare Interviu sau intrebari de grup

Elementele procesului de consimtamant informat Informatie orala si scrisa pe grade de instruire Afirmatia explicita ca studiul implica cercetare, cu descrierea procedurilor, duratei, identificarea procedurilor experimentale Riscuri si eventual discomfort anticipat Beneficii anticipate pentru subiecti sau altii Natura voluntara a participarii la studiu Capacitatea de a se retrage oricand

Enumerarea alternativelor Afirmatie legata de confidentialitate / anonimat Afirmatie legata de compensare / tratament medical Afirmatie legata de persoana de contact pentru intrebari legate de drepturile subiectilor, protocolul de cercetare, riscuri asociate protocolului

Costuri Consimatamantul informat trebuie sa transmita clar explicatia costurilor pentru care subiectul este responsabil.
Evaluarea riscurilor participantilor

Raportarea evenimentelor adverse
Probleme neanticipate Evenimente adverse serioase
Noi date pot duce la:

Reevaluarea riscului Modificarea formularului de consimtamant Terminarea prematura a protocolului de cercetare
Populatii vulnerabile
Copii Prizonieri Indivizi cu retard mental Dementa/ Coma/ Starea vegetativa Boli mentale Gravide Pacienti in urgenta
Consimtamant deplin informat

o Liber de coercitie fara teama / exploatarea puterii / pozitiei o Consimtamant oficial Nu este tacit ci explicit, scris!

o o o o Scopul si metodele studiului? Ce se asteapta de la participanti? Cum se colecteaza datele? Participantii pot sa comenteze / interpreteze datele ? o Se va publica cercetarea? o Care sunt beneficiile si rezervele in a fi participant la studiu?
Respect pentru copii

Consideratii legale: datoria de ingrijire Obtinerea consimtamantului informat de la copii
Managing Risks to Subjects

Adverse Event Reporting Unanticipated problems Serious adverse events New data May lead to: Reassessment of risk Changes to consent form or reconsent More frequent oversight by the IRB Early termination of the protocol
Healthy volunteers
Volunteers may not stand to benefit directly, but could ultimately contribute to development of a new therapy that the participant might then use. Require particularly close monitoring, because they can pose a risk to a volunteer's health or life.
Confidentiality
Unless you guarantee confidentiality you probably wont gain consent and you certainly wont obtain significant data. Once you agree confidentiality then this must be honoured (BUT: our duty of trust / promise is outweighed by our obligation to prevent harm to others). Must ensure that confidentiality is not breached directly (gossiping) or by accident (leaving notes lying around).
Anonymity
Confidentiality is best assured by anonymising collection of data. Anonymity is increasingly difficult as advances in technology are made
Respect for children

Legal considerations: duty of care Gaining informed consent from children Empowerment: giving children a voice
Choice of control
The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. (Helsinki 2000) Balance the need to answer the valuable question in a scientifically rigorous way, while minimizing risks and maximizing benefits to participants.
The Ethics Review Process

Frequently Asked Questions
1. How long will my review take? 2. Who can I contact to find out the status of my review? 3. Who can I contact for clarification of review comments? 4. When can I begin my research?
Research as burden or benefit?
Research as burden Subjects need protection
Research as benefit Subjects need access
Vulnerability
There is an order of preference in selecting subjects, for instance, adults before children (Belmont Report)
Exclude vulnerable subjects unless their participation is needed for scientific reasons (CIOMS)
Essential Elements of Ethical Research

Balance of Risks and Benefits Non-maleficence and Beneficence
Minimize risks to subjects Maximize benefits to individual subjects and to society Benefits should be proportional to or outweigh risks.
Risks in research
Defining risks
Probability and magnitude Types of risk Uncertainty
Minimizing risks Limiting risk
Benefits in research
Defining benefits Direct versus secondary benefits
Maximizing benefits
Balancing risks and benefits
Benefits and Risks in Research

[I]nterests other than those of the subject may on some occasions be sufficient by themselves to justify the risks involved in the research, so long as the subjects rights have been protected. The Belmont Report

Independent Review Minimize conflict of interest Public Accountability
Independent review of clinical research ensures the public that investigator biases have not distorted the approach, that ethical requirements have been fulfilled, and that subjects will not be exploited.
Criteria for IRB Review (45CFR.46.111

and 21CFR56.111)
Risks are minimized. Risks are justified by anticipated benefits, if any, to the subjects or the importance of the knowledge to be gained Subjects will be selected and treated fairly Informed consent is adequate

Informed Consent Respect for Persons Voluntary agreement to participate, based on understanding the objectives, risks, benefits, and alternatives of the research.
Key points
Integrity Fully informed consent Confidentiality Anonymity Respect for children

Respect for Enrolled Subjects Beneficence and Respect for Persons
Right to withdraw. Confidentiality of subject data. Informing subjects of new information and of study results. Monitoring subject welfare.
Balancing principles
Example: Randomized Controlled Trials Balancing the need for a rigorous design with the obligation to maximize benefits and minimize harms
Equipoise Randomization Choice of control
Choice of control
The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. (Helsinki 2000) Balance the need to answer the valuable question in a scientifically rigorous way, while minimizing risks and maximizing benefits to participants.

Etica in cercetarea tiinific Consimtamantul informat
Corin Badiu, 2011
Etica Definitii academice si practice

Ramura a disciplinelor filozofice, considerata stiinta de normare intrucat se ocupa de normele conduitei umane. [academic]
Procesul prin care se aplica valorile morale la situatii actuale de viata. [practic]
1. Fond, Scopuri, Obiective

2. Metodologia cercetarii 3. Participanti 4. Recrutare 5. Riscuri si Beneficii 6. Confidentialitate 7. Compensare
8. Conflict de Interese
9. Elaborarea si aplicarea consimtamantului Informat 10. Evaluarea prin comitete si institutii 11. Contract 12. Trialuri Clinice
13. Anexe
Anexe
Text Telefonic/email
Exemple de scrisori de consimtamant Ghiduri de observatie clinica Chestionare
Interviu sau intrebari de grup

Etica cercetarii clinice

Cerintele etice in cercetarea clinica au ca scop:
Limitarea posibilitatii de exploatare; Siguranta ca sunt respectate drepturile pacientilor in timp ce acestia ajuta la imbunatatirea cunoasterii.
Coduri etice si Ghiduri

Codul Nuremberg (1949) Declaratia de la Helsinki Raportul Belmont (1979) Ghiduri Internationale OMS (1993, 2002) ICH/GCP-International Conference on Harmonization- Good Clinical Practice
(1996)
(1964- 2000)
Perspective istorice
Tribunalul de razboi de la Nuremberg (1947) judecarea a
23 medici si militari germani care au comis crime de razboi si crime impotriva umanitatii. Teste inadmisibile efectuate cu scop de cercetare pe mii de prizonieri din lagarele de concentrare, fara a obtine consimatamant informat. Tuskegee Syphilis Study (1932-1972) Ca parte componenta a unui proiect de cercetare condus de serviciul public de sanatate din SUA asupra 600 de barbati de culoare, provenind din categorii sociale defavorizate, din care 400 erau infectati cu sifilis, au fost monitorizati timp de 40 ani. Consulturile medicale erau gratuite; totusi, participantii nu au fost informati asupra bolii. Chiar cand a aparut posibilitatea terapiei antibiotice cu penicillina in anii 1950, studiul a continuat pana in 1972, participantii neprimind tratament. In anumite cazuri, cand participantii erau diagnosticati ca avand sifilis de catre alti medici, cercetatorii au intervenit pentru a preveni tratamentul. Multi participanti au murit de sifilis in timpul studiului. Studiul a fost oprit in 1973 de catre Departamentul de Sanatate si Educatie din SUA doar dupa ce a fost mediatizat si a devenit un element politic.
Nuremberg, Germany December 9, 1946 to August 20, 1947

Necesar acordul voluntar nainte de participare
Responsabilitatea investigatorului de a obine consimmntul

Informaiile obinute prin utilizarea subiecilor umani nu ar putea fi obtinute prin niciun alt mod
Tuskegee Syphilis Study
Raportul BELMONT
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
Distinctie intre cercetarea clinica si asistenta medicala
Raportul Belmont
Stabileste principiile etice i liniile directoare pentru Protectia Subiectilor Umani in cercetare (aprilie 1979) A stabilit trei principii de baz, care sunt piatra de temelie a reglementrilor care implic protecia subiectilor umani in cercetare
Respect pentru pacient; pastrarea independentei pacientului Cercetarea trebuie sa aduca beneficii starii de sanatate a pacientului Expunerea corecta a avantajelor si dezavantajelor
Folosirea Talidomidei - Talidomida a fost
folosita in anii 1950 pentru a combate disgravidia. In perioada utilizarii sale, nu s-a transmis gravidelor faptul ca medicamentul era in curs de investigare, in faza de testare pentru obtinerea autorizatiilor. Dupa ce multe femei din Europa, Canada, si U.S.A au fost tratate, s-a descoperita ca are efecte teratogene, determinand maformatii fetale severe. Talidomida a fost oprita de la comercializare imediat in intreaga lume. Din pacate, aproximativ 12.000 copii s-au nascut cu malformatii severe datorate talidomidei.
Experimente de Iradiere(1940s 1960s) Oficiali
din U.S.A au studiat efectele radiatiei prin experimente pe pacienti spitalizati, femei gravide, copii cu intarziere mentala, cadre militare sau puscariasi. Putini dintre participantii la experimente au dat consimtamant informat. Majoritatea nu stiau ca sunt expusi la materiale radioactive. Oficialii proiectului Manhattan au autorizat experimente din timpul razboiului pentru a stabilii standarde de sanatate si siguranta pentru sutele de muncitori din fabricile de armament atomic.
Eventimente Santinela
Crime de razboi naziste
Procesul de la Nuremberg (1948)

Declaratia de la Helsinki (1963) Raportul Belmont (1977)
Experimente de iradiere
Tuskegee Syphilis study
Raspunsul la aceste abuzuri in cercetare

Atrocitatile naziste in al doilea razboi mondial au atras atentia asupra lipsei standardelor internationale in cercetarea cu subiecti umani si au dus la formularea Codului de la Nuremberg (1948). Dezastrul talidomidei a dus la adoptarea "Amendamentului Kefauver" (1962) din Actul asupra alimentelor, cosmeticelor si medicamentelor, solicitand fabricantilor de medicamente sa puna la dispozitia FDA normele de siguranta si eficacitate a produselor lor iar medicii au fost obligati sa obtina consimtamant informat de la pacientii care ar putea primi o medicatie in curs de investigare. Declaratia de la Helsinki a rezumat munca Asociatiei Medicale Mondiale in 1964 (reevaluata in 2000) construita pe codul de la Nuremberg si este baza Normelor de Buna Practica Clinica folosite azi.
Actul National de Cercetare (1974) care a aparut ca urmare a raspunsului la Studiului Tuskegee sifilis, instaureaza necesitatea ca subiectii umani sa fie protejati si sa beneficieze de achizitiile cele mai recente in cercetare, fiind baza de pornire pentru Raportul Belmont.
Declaratia de la Helsinki (Asociatia Medicala Mondiala)

Aduce principiile etice utilizate de ctre medici care efectueaz cercetarea uman A afirmat autonomia individului Declaratie adoptata universal pentru a asigura drepturile i siguranta subiecilor umani inclusi in cercetare clinica
http://www.wma.net/en/30publications/10policies/b3/index.html
Declaration of Helsinki
World Medical Association, 1964. Ultima evaluare - 2008 Cercetarea cu subieci umani se justific doar atunci cnd gradul de risc pentru subieci nu depete importana cunotinelor care urmeaz s fie dobndite. DH este baza pentru normele de buna practica clinica utilizate n prezent.
Declaratia de la Helsinki
Probleme abordate: Cercetarea clinica ar trebui s se bazeze pe experimente de laborator (in vitro) i animale (in vivo) Protocoalele experimentale trebuie s fie revizuite de ctre un comitet independent Acordul de participare la cercetare in scris-consimmntul informat Cercetrile efectuate de ctre persoane fizice calificate medical / si stiintific Riscurile i beneficiile studiului Impactul / respectul asupra vieii private a persoanei Publicarea rezultatelor cercetrii
Institutii de reglementare etica in Romania

Comisia nationala de etica Agentia nationala a medicamentului
Ordin 1224/2004 pentru aprobarea Ghidului privind studiile de siguranta nonclinica necesare in vederea efectuarii studiilor clinice pentru evaluarea medicamentelor ORDIN 615 /2004 pentru aprobarea Reglementrilor privind implementarea regulilor de buna practica n desfurarea studiilor clinice efectuate cu medicamente de uz uman
Fond, Scopuri, Obiective
Care este subiectul cercetarii?

Ce scopuri se vor indeplini prin cercetare? Care sunt principalele intrebari la care se doreste raspuns? Descrie pe scurt fondul stiintific al studiului pagina
Metodologia cercetarii
Secventa logica de evenimente din cadrul studiului (protocol)

Cum se vor obtine datele? Descriere detaliata pentru fiecare metoda. Pune urmatoarele intrebari:
Cat dureaza interviul/chestionarul/observatia experimentala? Cand (in ce perioada) va avea loc? Unde va avea loc? Participantii vor avea posibilitatea sa intervina in chestionar/studiu? Daca da, ofera detalii.
Care sunt implicatiile /aplicatiile cercetarii?


Ce inseamna?
Participanti
Cine sunt participantii? Organizatii? Indivizi? De ce au fost alesi pentru studiu? (criterii de excludere / includere) Cati sunt? Argumenteaza dimensiunea esantionului
Recrutare
Cum veti obtine o lista a potentialilor participanti? Sistem de contact telefonic
Email
scrisoare ?
Grupuri de studiu: Control, Test
Riscuri si Beneficii
Standarde de aplicare:
Nu exista risc minim anticipat. Participantii vor fi informati despre natura studiului si modalitatii de participare, inclusiv asupra faptului ca se pot retrage oricand. Participantii (si raspunsurile lor privind includerea in studiu) vor fi luate ca atare
Confidentialitate
Cine va avea acces la date?

Se va inregistra interviul? Cum va fi protejata identitatea participantilor? Se codifica toate datele? Cum se stocheaza datele in timpul studiului? Cand se distrug datele? Cum se va pastra confidentalitatea ? Se va exclude orice informatie de identificare?

Fundamental in cercetarea pe subiecti umani
Este un proces si nu un formular.
Formularul este doar documentul care atesta ca procesul de informare liber consimtita a avut loc.
Se va obtine consimtamant informat scris?

De la nivel institutional? De la decan/ rector?
Consimtamantul informat trebuie obtinut de la toti participantii

Interviu consimtamant scris Chestionare Prin completarea chestionarelor
Pentru studii avand ca subiecti copii, consimtamantul scris al parintilor / tutorilor este obligatoriu
Cum obtinem CI?

Variaza in functie de designul studiului si natura participarii Verbal vs. Scris
Investigator vs. Co-investigatori / asistenti

Elementele procesului de consimtamant informat Informatie orala si scrisa pe grade de instruire Afirmatia explicita ca studiul implica cercetare, cu descrierea procedurilor, duratei, identificarea procedurilor experimentale Riscuri si eventual discomfort anticipat Beneficii anticipate pentru subiecti sau altii Natura voluntara a participarii la studiu Capacitatea de a se retrage oricand

Enumerarea alternativelor Afirmatie legata de confidentialitate / anonimat Afirmatie legata de compensare / tratament medical Afirmatie legata de persoana de contact pentru intrebari legate de drepturile subiectilor, protocolul de cercetare, riscuri asociate protocolului

Costuri Consimatamantul informat trebuie sa transmita clar explicatia costurilor pentru care subiectul este responsabil.
Evaluarea riscurilor participantilor

Raportarea evenimentelor adverse
Probleme neanticipate Evenimente adverse serioase
Noi date pot duce la:

Reevaluarea riscului Modificarea formularului de consimtamant Terminarea prematura a protocolului de cercetare
Populatii vulnerabile
Copii Prizonieri Indivizi cu retard mental Dementa/ Coma/ Starea vegetativa Boli mentale Gravide Pacienti in urgenta

o Liber de coercitie fara teama / exploatarea puterii / pozitiei o Consimtamant oficial Nu este tacit ci explicit, scris!

o o o o Scopul si metodele studiului? Ce se asteapta de la participanti? Cum se colecteaza datele? Participantii pot sa comenteze / interpreteze datele ? o Se va publica cercetarea? o Care sunt beneficiile si rezervele in a fi participant la studiu?
Respect pentru copii

Consideratii legale: datoria de ingrijire Obtinerea consimtamantului informat de la copii (de la 6-8 ani)
Confidentialitate
Fara garantarea confidenialitatii, nu se poate semna acordul de consimtamant. Odat ce suntei de acord cu confidenialitatea, atunci acest lucru trebuie s fie onorat (DAR: este de datoria noastr sa prevenim efectele negative pentru alii). Trebuie s se asigure c nu este nclcata confidenialitatea n mod direct (brfe) sau de accident (lsnd notite despre caz, bilete de iesire, foi de observatie).
Anonimitatea
Confidentialitatea este asigurata prin codificarea anonima a colectiei de date.
Anonimizarea este din ce in ce mai dificila, pe masura progresului tehnologic
Conflictul de Interese
O situaie n care considerente financiare sau de alt natur cu caracter personal pot influenta, sau poate fi perceput de ctre alii ca generatoare de eroare pentru judecata profesional.
Conflict de Interese
Financiar
Actiuni la firma farmaceutica, consultant, speaker
Non-financiare
Recunoatere in domeniu, dorina de a avansa teoria cuiva Nu suntem n msur s eliminam conflictele de interes, dar exist i alte opiuni: reducerea, evitarea sau prezentarea explicita a acestora
Conflict de Interese in cercetarea clinica

Imposibil de eliminat in totalitate
Pot fi financiare, personale, individuale sau institutionale Astazi: focuseaza pe conflictul financiar Normele de etica obliga investigatorii sa fie atenti la toate tipurile de conflict de interese
De obicei, rezult din rolul dublu al unui cercettor De exemplu, un profesor / cercetator care doreste s colecteze date de la proprii studenti, sau un alt tip de relaie n care cercettorul are un rol de evaluare n raport cu participanii
Potenialii participani pot simti o presiune de a participa ce rezult din relaia de putere dintre profesor / student i nu se simt foarte confortabil sa refuze participarea
Impactul asupra drepturilor i bunstrii persoanelor implicate in cercetare Existenta unor conflicte de interese poate duce la erori in metodologia studiului si pierderea ncrederii publicului
Impactul asupra integritii datelor depuse la autoritile de reglementare i reviste
Digital Data Ethics

Simple adjustments to the ENTIRE image are usually acceptable.
Selectively manipulating one area of the image is questionable. Cropping an image is usually acceptable. If used, software filters must be noted in the figure caption. The more processing you have to do, the more ethically problematic the manipulations become.
Tipuri de date
Body temperature Body weight Room temperature, humidity Food/water use Animal behavior (e.g., sleeping, aggression) Assay data
Data Selection & Retention

Be careful how you pick and chose Be consistent with regard to high background, artifact, low confidence values, and noise (versus signal) When reporting your data, disclose what you did:
Two obese rats were excluded because The first three data points were excluded because
Dilemmas with Gels & Digital Data
Gels, X-Rays, photos are considered DATA
Ale cui sunt datele?

Angajati si studenti care prin activitatea curenta se leaga n orice mod de practica responsabilitii in cercetare trebuie s fie atribuiti Clinicii. Schimburile de material de cercetare cu cercettori din afara trebuie s fie ncadrate n acorduri scrise. Clinica poate fi compensat pentru astfel de schimburi.

Ce inseamna?
Pastrarea datelor
Caiet de laborator semnat si datat Scris LIZIBIL Fara pasta corectoare Se taie cu o linie, se semneaza si se dateaza. Fara Postit (sticky notes). Fara pagini albe.
Author Requirements*
Authorship credit should be based on: 1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; and 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published. Authors should meet conditions 1, 2, and 3.
*Intl Comm of Medical Journal Editors. Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. November 2009.
http://www.icmje.org/ethical_1author.html
Authorship
Those credited with authorship should be able to take public responsibility for the research.
Authorship*
Acquisition of funding, collection of data, or general supervision of the research group, alone, does not justify authorship.
*Intl Comm of Medical Journal Editors. Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. November 2009.
Authorship
Decide up front who will work on the manuscript and what the order of authors will be.
(Not all people working on the project will meet authorship requirements).
Research Misconduct
Fabrication (creating data) Falsification (changing data) Plagiarism (using anothers words or ideas without giving them credit).
This includes cutting and pasting from the Internet.
Why is Misconduct Bad?

It affects the integrity of science as a profession (which potentially adversely affects research funding)
It is not collegial
Propels further generation of bad data as the initial data foundation is bad
Misconduct Research
Survey of 3247 researchers:
28% admitted to poor record keeping 16% admitted to changing the design, methodology, or results of a study in response to pressure from their funding source 15% admitted to dropping observations/data points based on a gut feeling 10% admit to giving authorship to people who didn't earn it
ref: Martinson et al. Nature 2005;435:737-738
What to do if you suspect misconduct

Dont assume you are right Dont accuse Try to verify your suspicion (there may be an acceptable reason for what is going on) Ask yourself, what is my motive for getting involved? Ask the advice of someone you trust
Issues in Animal Research

Your Guide: Guide for the Care and Use of Laboratory Animals info about vet care, housing, pain control euthanasia, etc.
(http://www.nap.edu/readingroom/books/labrats/)
Issues in Animal Research

Have you attempted to REPLACE animals with another model? Have you REDUCED the number of animals to the minimum needed for statistical purposes? Have you REFINED your lab techniques so that animal pain and suffering are as low as possible? Is your protocol approved by the CCF Institutional Animal Care and Use Committee?
Identification
Make sure your animals are clearly identifiable, whether singularly or in groups.
Options include cage labels, neck labels, tattoo, microchip, etc.
Housing Your Animals
Consider the animal species Housing should consider size of animal, temperature, bedding needs, food, clean water, light, noise, humidity, contact with other animals, air exchange, vibration, etc. Keep the cages clean, and the animals free from harm from other animals. (This includes avoiding crowding within a cage).
Avoiding Animal Stress
If possible, before starting your project, CONDITION your animals to their environment, procedures, and research personnel.
Pain/Suffering
An animal with signs of pain or distress not predicted in the protocol, must have the pain or distress alleviated promptly. Alleviation of such pain or distress must take precedence over completing a project. If this is not possible the animal must be euthanized without delay.
Moral problem in clinical research

The goal of clinical research is generation of useful knowledge about human health and illness Benefit to participants is not the purpose of research
(although it does occur)
People are the means to developing useful knowledge; and are thus at risk of exploitation
CONCLUZII
Etica n cercetarea ncepe cu cererea de finanare
Se aplic tuturor celor implicai n procesul de cercetare Se ncheie cu publicarea i consecintele (clinice si stiintifice) acesteia

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Metodologia cercetrii tiinifice

Concepte, necesiti i atitudini

Corin Badiu, 2007

Cercetarea stiintifica (1)

Cercetarea stiintifica (2)

Cercetarea stiintifica (3)

interpretarea rezultatelor diseminarea acestor rezultate

CATEGORII ALE CERCETARII

1.Cercetarea Empirica si Teoretica (1)

1.Cercetarea Empirica si Teoretica (2)

1.Cercetarea Empirica si Teoretica (3)

1.Cercetarea Empirica si Teoretica (4)

Cercetarea in Domeniul Medical (1)

Cercetarea in Domeniul Medical (2)

Cercetarea in Domeniul Medical (3)

Cercetarea in Domeniul Medical (4)

2.Cercetarea Fundamentala si Aplicata(1)

2.Cercetarea Fundamentala si Aplicata(2)

2.Cercetarea Fundamentala si Aplicata(4)

2.Cercetarea Fundamentala si Aplicata(5)

3.Triunghiul Cercetarii in Domeniul Sanatatii (1)

trei categorii interconectate operational:

3.Triunghiul Cercetarii in Domeniul Sanatatii (4)

3.Triunghiul Cercetarii in Domeniul Sanatatii (5)

Fundamentele Stiintifice ale Cercetarii (1)

Fundamentele Stiintifice ale Cercetarii (2)

Fundamentele Stiintifice ale Cercetarii (3)

Fundamentele Stiintifice ale Cercetarii (4)

Deductia si Sansa (6)

Deductia si Sansa (7)

Fundamentele Stiintifice ale Cercetarii (5)

Fundamentele Stiintifice ale Cercetarii (6)

Fundamentele Stiintifice ale Cercetarii (7)

Fundamentele Stiintifice ale Cercetarii (8)

Fundamentele Stiintifice ale Cercetarii (9)

Fundamentele Stiintifice ale Cercetarii (10)

Fundamentele Stiintifice ale Cercetarii (11)

Fundamentele Stiintifice ale Cercetarii (12)

Fundamentele Stiintifice ale Cercetarii (13) 4.Ipoteza(4)

ale unor boli si a explica distributia bolilor in populatii

Fundamentele Stiintifice ale Cercetarii (14)

Pe scurt aceste metode includ:

Fundamentele Stiintifice ale Cercetarii (15)

Fundamentele Stiintifice ale Cercetarii (16) 4.Ipoteza(7)

Fundamentele Stiintifice ale Cercetarii (17) 4.Ipoteza(8)

Fundamentele Stiintifice ale Cercetarii (18)

Metodologia cercetrii tiinifice

Ipoteza de lucru Organizarea studiului Tipuri de studii

Corin Badiu, 2011

Redactarea unui protocol de 10 pagini pentru un studiu real / ipotetic

Sectiuni ale protocolului de studiu

Identificati problema studiului enuntata in rezumat

Originile unei probleme de cercetare

A fi deschis la idei si tehnici noi

Caracteristicile unui studiu FINER

Caracteristicile FINER Criterii de Noutate

Caracteristicile FINER Criterii de Etica

Caracteristicile FINER Criterii de Relevanta

Pentru clinicieni, sanatatea publica sau politicile de sanatate

Probleme si solutii: Planul nu este FINER

Fara interes, noutate sau relevanta Evaluare etica inadecvata

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