legal and ethical issues in (nursing) reseach - med uni...

Legal and ethical issues in

(nursing) reseach

September 12, 2014

• Arno Škrabanja • Biochemist • Pharmaceutical Development Akzo Nobel

(Organon) from 1988 to 2001 • Development of SOPs and GLP • Dept of Epidemiology UM as coordinator of

research 2001 – 2006 • Quality Coordinator since 2006 CTCM • Member national commission Basic Rules and

Organization for Clinical Researchers (BROK)

Legal and ethical issues

Why do we need legislation?

• To protect the participant in a study • Safety • Personal integrity and privacy

• Transparency of all actions • During the study and afterwards

• Procedures and responsibilities must be documented

• European Community • Directives

• Clinical Trial Directive (implemented in NL in WMO) • Data Protection (WBP) • Medicine (WOG)

Law and Legislation

• European Community • Directives

• Clinical Trial Directive (implemented in NL in WMO) • Data Protection (WBP) • Medicine (WOG)

• Worldwide:

• FDA Code of Federal Regulations (US) • 21 CFR, parts 11, 50, 54, 56, 312 and 314

• ICH Guidelines (Good Clinical Practice and 70 other guidelines) • ISO standards

• ISO 14155 (research with medical devices) • ISO 15195 and 15189 Labs • HACCP for food additives

Law and Legislation

• Within EU: • Local laws, e.g. in NL:

• WMO • WBP • WOG

• Each country judges legal and ethical issues separately

• Change in 2016: • For interventional drug studies one approval for whole EU

Law and Legislation

• Types of research:

• Interventional

• Observational

What is an intervention?

• All research imposing rules of conduct on participants

• Participants are treated different from regular care

• Participants are treated different from regular care • If the study design by means of a randomisation

determines whether a particular treatment is given to participant (randomisation)

• Diet YES • Questionnaire NO • Blood sample Sometimes

Intervention?

• During different walking tasks healthy volunteers are measured with fNIRS (functional Near Infrared Spectroscopy) Also several questionnaires are collected (degree of physical activity, fear of falling, self-rated quality of life) and participants must perform a number of walking tasks. In total, the study takes about three hours, including rest.

• There are no invasive measurements used. While walking blood pressure is continuously measured and wireless fNIRS equipment is worn.

Intervention or not?

• Description of the proposed research, including the information leaflet for potential participants was mailed to the local MREC. The committee found that it is a minor burden for participants, without invasive measurements, therefore it was no intervention and therefore not liable to WMO. No extended application will be required.

• During different walking tasks Parkinson patients are measured with fNIRS (functional Near Infrared Spectroscopy) Also several questionnaires are collected (degree of physical activity, fear of falling, self-rated quality of life) and participants must perform a number of walking tasks. In total, the study takes about three hours, including rest.

• There are no invasive measurements used. While walking blood pressure is continuously measured and wireless fNIRS equipment is worn.

• Again an email was sent to the recognized ethical committee. In this case they concluded that the burden for patients with Parkinson's is such that it is subject to WMO.

• Intervention? • If so, approval is needed always

• Proper protocol needed • Permission from an authorized MREC • Written informed consent for the actions and data as

traceable to the individual, also consent to the processing of data

• Medicines

• Medical devices

• Food supplements

• Surgical techniques

• Behavioral and psychological research • Which influences behavior

• Interviews and surveys

• Which influences behavior

Types interventional research

• What is drug research?

• The purpose of the study is the evaluation of efficacy and safety of a (new) drug

• All research with unregistered and registered drugs involving an intervention: GCP requirement for all participants (sponsors and investigators)

• Non-intervention studies with medicines are non GCP

Indeling onderzoek : • Intervention? • If not, observational

• Proper protocol • Statement of recognized MREC depending on the code in the

hospital, or magazine editors (because of publication) • No written informed consent needed • But: if data can be traced to the individual person, informed

consent is needed

• What makes research ethical?

• What makes research ethical? • Patients are informed and have no objection

• As little as possible direct identifiable information

• Normal care is always given

• Protocol is approved by an accredited MREC

• Information and objection • Is information given orally enough?

• Must a physician always sign the informed consent? NO

• Is it possible to end participation without reason?

• Special participants • incompetent subjects • children • demented elderly • mentally handicapped

Information and objection

• Incompetent subjects: • Who gives informed consent?

• Legal representative

• Mother agrees with study, is that sufficient? NO

• Old lady forgot her glasses, daughter signs informed consent, is that sufficient?

Informed consent procedure • Only investigations in subjects who personally give consent

and sign and date the informed consent form themself

• Not force or unduly influence a subject to participate in an investigation or to ensure continuing

Legal and ethical isues

Informed consent procedure • The informed consent form signed and dated by the subject in

person*, and by the person who has held the discussion on the consent, before a subject participates in a clinical trial

* Or the legal representative of the subject

• Partipants should get: • Adequately written information

• Reasonable reflection period

• Privacy: • Anonymous data preferred

• Separation of data and personal information

• Anonymous? • Name and date of birth

• Age

• Gender

• DNA

• Judgement by the MREC

• study is necessary for new insights • no alternatives • risks to subjects acceptable • appropriate methodology • performed by competent persons • compensation for research subjects does not

affect the giving of consent

• For an international, EU funded research (for fall prevention training for the elderly) a CMO request is made . Five clinical centers, each from a different country, are involved in the research.

• How to submit the application?

Multicenter research

• For an international, EU funded research (for fall prevention training for the elderly) a MREC request is made . Five clinical centers, each from a different country, are involved in the research.

• How to submit the application? • For each center separately at a local recognized

committee.

Multicenter research

• Sponsor:

• Investigator:

Responsibilities

• Sponsor: • An individual, company, institution, or organization which takes

responsibility for the initiation, management, and/or financing of a clinical trial.

• Investigator:

Responsibilities

• Sponsor: • An individual, company, institution, or organization which takes

responsibility for the initiation, management, and/or financing of a clinical trial.

• Investigator:

• A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.

Responsibilities

• Sponsor-Investigator: • An individual who both initiates and conducts, alone or with

others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

Responsibilities

• A sponsor may delegate tasks, but not responsibilities

• An investigator may delegate tasks to qualified personnel, but not responsibilities for performing the study and safety of participants

• All delegated tasks must be written down in protocol/contract and/or delegation list

Delegation

Investigator

• Take responsibility for the proper execution of clinical research

• qualification by education, training and experience

• provide evidence of such qualifications through an updated

curriculum vitae and / or other relevant documentation

• Be fully aware of the proper use of the investigational product

• Permit control of the study

• At request allow direct access to any documents related to the study

• Maintain a list of persons with relevant qualifications to which significant research-related obligations have been delegated (delegation log)

• Adequately qualified staff and adequate facilities available for the

planned duration of the study

• Ensure that all persons who participate in the study are adequately informed about the protocol, the research products and their obligations and duties regarding the examination

• Ensure that appropriate medical care is provided to a subject in case of adverse events, including clinically significant abnormalities in laboratory values associated with the investigation

• Inform the GP of the subject of the subject's participation in the study (if the subject has a family doctor and agrees)

• Attempt to determine the reason(s) for early withdrawal from clinical studies

• Record any deviation from the approved protocol and explain

• Submit deviations or changes, the reasons for it and, if applicable, the proposed amendment(s) as soon as possible to the MREC, the

sponsor and (if required) the competent authority (ies)

• Trial Master File

• All documentation used before, during and after closure of the study; arranged in a proper way and stored at one location

• Multicenter studies: one (master) TMF and local ISF

Administration

1 Correspondence [hard copies]

• Internal study correspondence

• Monitor correspondence

• Sponsor correspondence, if applicable

2 Study Staff meetings [hard copies]

3 Quality system (Standard Operating Procedures (SOPs))

[originals or copies, depending on initiator of the document]

4 Study Staff [copies]

• Delegation log

• Current CVs (< 2 years old) of all study staff (signed and dated)

• Qualification records

• Training records (including GCP): protocol and procedure training for study personnel

5 Planning and progress of the study

[copies or originals - depending on initiator of the document]

6 Financial aspects of the trial (unless stored elsewhere) [originals]

7 Protocol [originals]

• Previous and current versions of the protocol

• Protocol Signature Pages all centers

8 Previous and current blank versions of the CRF [hard copies]

(including diary and questionnaires)

9 Previous and current versions of subject information [hard copies]

• Blank set of Informed Consent Forms

• Advertisement text

• Information given to the subject (IMP, subject ID/safety card)

What can happen during a study • Adverse events • Adverse reactions • Serious adverse events • Serious adverse reactions • Suspected unexpected serious adverse reactions

Safety

Reporting of AEs and SAEs • Report all SAEs to the sponsor within 24 hours and write immediate

reports quickly followed by detailed, written reports, in which the subjects are indicated by code,

• Follow relevant legal requirements regarding the reporting of unexpected serious adverse reactions to the competent authority (ies) and the MREC

• When reporting a death to the sponsor and the MREC provide any additional information requested (e.g. autopsy reports and death certificates)

• What is the difference between an adverse event and an adverse reaction?

Adverse events

• What is the difference between an adverse event and an adverse reaction?

• A reaction is related to the study!

Adverse events

• Patient falls on toilet during measurements, result is a bruised rib.

• How should this be registered/resolved?

Adverse events

• Patient falls on toilet during measurements, result is a bruised rib.

• How should this be registered/resolved? • It is an adverse event and has to be reported to the

sponsor. Only severe adverse events are reported immediately to local MREC. Maintain contact with the patient to see how the recovery was after the fall.

Adverse events

• How to control proper execution of a study?

• Trust investigators • Check by randomly sampling

• Monitoring • Appoint monitors • Provide adequate monitoring

• Responsibilities monitor

• Audit

• Sponsor determines need

Quality Assurance Quality Control

Who? Auditor Monitor

What? Systematic review of study related activities and documents Check everything in detail

When? Often once Monitoring visits before, during and after study

Summary "Are the right things done?" “Are the things done right?”

Source: M. Lemmens CTCM 61

• Intervention vs observation • Drug research vs research with drugs • Children vs adults • Etc. etc.

What is needed for which type op research?

Clinical Trial Center Maastricht

What would you do yourself? http://ori.hhs.gov/thelab

Thank you for your attention

legal and ethical issues in (nursing) reseach - med uni...

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