Metodologia cercetării ştiinţifice

Etica in cercetarea ştiinţifică

Corin Badiu, 2015

 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]
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
Protocolul de evaluare etica in cercetare

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
 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)
 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 (1964- 2013)

• Raportul Belmont (1979)

• Ghiduri Internationale OMS (1993, 2002)

• ICH/GCP-International Conference on
Harmonization- Good Clinical Practice (1996)
 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 syphilis, 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 penicilina 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

 Required voluntary consent

prior to participation

 Investigator responsibility to
obtain consent

 Information gained by using

human subjects would be
unprocurable any other way
Tuskegee Syphilis Study
 Perspective istorice

• 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.
 Perspective istorice
• 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 razboilui 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)

• Experimente de iradiere Declaratia de la

Helsinki (1963)

• Tuskegee Syphilis study Raportul Belmont

(1977)
 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)

• Articulated ethical principles for use by

physicians conducting human research
• Affirmed the autonomy of the individual
• Universally adopted to ensure the rights
and welfare of human subjects of
research
 Declaratia de la Helsinki
• World Medical Association, 1964.

• Last amended 2013 (64th WMA General Assembly,

Fortaleza, Brazil, October 2013)

• Ethical Principles for Medical Research Involving

Human Subjects

• Take home point: Research with human subjects is

justified only when the degree of risk to subjects does
not exceed the humanitarian importance of the
knowledge to be gained. The DH is the basis for
Good Clinical Practice used today.
 Declaration of Helsinki
Issues addressed:
 Research with humans should be based on
laboratory and animal experimentation
 Experimental protocol should be reviewed by
independent committee
 Informed consent
 Research conducted by medically /
scientifically qualified individuals
 Risks and benefits
 Privacy of the subject
 Publication of research results
 Raportul BELMONT
National Commission for the Protection of Human Subjects of Biomedical
and Behavioral Research

• Distinction between clinical research

and clinical practice
 The Belmont Report

Ethical Principles and Guidelines for the

Protection of Human Subjects of Research
(April, 1979)
• Established three basic principles which are
the cornerstone of regulations involving
human subjects protection
 Autonomy / respect for persons
 Beneficence
 Justice
 Federal regulations

• 1991 Federal Policy for Protection of

Human Subjects (The Common Rule)
 Adopted by all agencies which conduct,
supervise, regulate, fund or sponsor
human research
 Two major requirements:
• Informed Consent
• IRB approval
 Romanian regulations
• National ethics committee

• National Drug Agency & Medical Devices

• Nonclinical studies research guide

 MHO 1224/2004 according to International
Conference for Harmonisation – ICH, Committee for
Proprietary Medicinal Products - CPMP guide 286/95

• Good clinical practice regulations - MHO 615/2004

 Ethical framework: 7 principles

• Valuable scientific question

• Valid scientific methodology
• Fair subject selection
• Favorable risk-benefit evaluation
• Independent review
• Informed consent
• Respect for enrolled subjects
Emanuel E, Wendler D, Grady C. What makes clinical research ethical? Journal of the
American Medical Association 2000; 283(20):2701-11
 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
 ½ 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?

 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.
 Procesul de consimtamant informat

 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
 Procesul de consimtamant informat

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
 Procesul de consimtamant informat

• 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
 Procesul de consimtamant informat

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!
 Consimtamant deplin informat
o Scopul si metodele studiului?
o Ce se asteapta de la participanti?
o Cum se colecteaza datele?
o 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)
 Conflict of Interest

• Financial
 Equity interest, consultant, paid speaker
• Non-financial
 Recognition, desire to advance one’s theory
• You might not be able to eliminate your
conflicts of interest, but there are other
options: reduce, avoid, disclose
 Conflict of Interest in Human
Research Studies
• Impossible to eliminate all conflicts of interests

• Types can be financial, personal, individual, or institutional

• Nowadays: focuses on financial

• Nevertheless, ethics dictates for investigators to be

sensitive to all types
 Conflicts of interest

• Usually resulting from a researcher’s dual role

e.g. a teacher/researcher wanting to collect data

from her/his own students, or another type of
relationship where the researcher has an
evaluative role in relation to participants

• Issue:
• Potential participants may feel some pressure to
participate resulting from the power relationship
between teacher/student and not feel completely
comfortable saying ‘no’ to participation
 What is a Conflict of Interest?

• A situation in which financial or other

personal considerations may bias, or be
perceived by others as biasing,
professional judgment or action.
 Why Do We Care About
Conflicts?

• Impact on rights and welfare of subjects

• Appearance of bias lead to loss of public confidence
• Impact on integrity of data submitted to regulators
and journals
 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.
Dilemmas with Gels & Digital Data

Gels, X-Rays, photos are considered 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…
 Who Owns “Your” Data & Materials?
• Employees & medical students that relate in any way to
his/her job/research responsibilities must be assigned to
the Clinic.

• Exchanges of research material with outside researchers

must be framed in written agreements, since further
discoveries may be made using the material. Clinic may
be compensated for such exchanges.
 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
 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. http://www.icmje.org/.
 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 another’s 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…

• Don’t assume you are “right”

• Don’t 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
 CONCLUSIONS

• Ethics is research starts with grant application

• Applies to all involved in research process

• Ends with publication and further follow - up

(clinical & scientific)