Metodologia cercetrii tiinifice

Etica in cercetarea tiinific

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
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
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)

Conflict of Interest
Financial

Equity interest, consultant, paid speaker

Non-financial

Recognition, desire to advance ones 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 researchers 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 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

CONCLUSIONS
Ethics is research starts with grant application
Applies to all involved in research process
Ends with publication and further follow - up
(clinical & scientific)