Curso de buena practica clínica y ética e investigación conductual

Fundation for best practices

Good clinical practices, 13 principles for quality process, established by the internal conference on
Harmonization, FDA published principles, all NIH national institutes of health say all clinical
research must use the good clinical practice

Principles:

1. Trials should be conducted with ethical principles thah come from the declaration of
Helsinki
2. Risks, benefits and alternative procedures need to be weighed prior to designing and
beginning a trial. They should also be discussed in detail with the perspective research
participant
3. The rights, safety and welfare of the research participant override the interests of the
study, society and science. The advancement of medicine is never the most important
factor in research: therefore, investigators must never sacrifice the interests and rights of
study subjects to ensure completion of a trial
4. The proposed study should be based on sound scientific data
5. Trials should be described in a clear and detailed protocol
6. Trials should be conducted in accordance with the protocol that has received prior
approval by an Institutional Review Board or ethics committee
7. Medical care within the context of a trial should be the responsibility of a qualified
physician, dentist or other health care provider
8. Each individual on the study team should be qualified by education, training and
experience to perform their designated study responsibilities
9. Freely given informed consent should be obtained from every participant prior to their
participation
10. All trial information should be recorded, handled, and stored in a way that allows accurate
reporting, interpretation and verification
11. The confidentiality of participants records and their privacy should be protected in
accordance with all applicable federal and local regulation
12. Systems with procedures that assure quality of every aspect of the trial should be
considered and implemented

A new definition of clinical trails by NIH

“any research study in which one of more human subjects are prospectively assigned to one or
more interventions (which may include placebo or other control) to evaluate the effects of those
interventions on health-related biomedical or behavioral outcomes

Doing good clinical practice helps by study may run more smoothly, helps protect research
participants, helps prevent non-compliance issues, well-run studies yield quality data, high-quality,
reproducible findings

Roles and responsabilities:

  Sponsor: works for federal funding agency, industry, or foundation. Reviews grants,
monitors progress of the study
 Institutional review Board (IRB): reviews and approves studies, helps protect participant
safety, ensures high standars
 Monitor/auditor: ensures that proper study procedures are being followed, ensures study
protocol is carried out consistently, works on multi-site studies
 Principal Investigator (PI): study lead, generates ideas, obtains funding, manages all
aspects
 Coordinator: day to day manager, keeps communication lines open
 Research assistant (RA): recruits participants, collects data,
 Data manager: oversees data collection, oversees data storage, prepares data for analysis
 Statistician: consults with study team, answers study questions
 Co-Investigator: partners with PI, provides expertise
 Research Nurse: Licensed nurse, handles medical procedures
 Interventionist: special training, clinical psychologist, therapist, or educator
 Office of research integrity: oversees investigations of misconduct

Module 2: Research protocol

Challenges on research

Its important to document deviations on research protocol for systematic and random error

Elements of a protocol

Clinical protocol: used to guide the conduct of the study, description of study operations from
start to finish

IRB protocol: required to receive IRB approval to conduct the study and emphasizes research
ethics and participant safety

Commonly required IRB protocol elements:

- Objectives
- Methods
- Quality control and assurance
- Ethics/protection of human subjects
- Data handling and record keeping
- Background and significance (evidence-based practice)

Methods: participant eligibility, study procedures, data analysis

IRB protocol with too little info: team member confusion, IRB resistance

Participant recruitment cannot begin until IRB approval is received, until then plan, gather
supplies, train

Supporting documents for a study

Standard operating procedures SOP, help ensure that every team member understands what they
are doing and how, when, and why it should be done

A procedures manual is a collection of standard operating procedures (SOPs), compiled into a

how-to manual

Data safety monitoring plan: outlines the steps to ensure the safety of participants and the
integrity of a trials data

Consort flow chart: demonstrates how participants move through the study, when and why
dropout is occurring, and whose data remained in the final data set

Use to evaluate the scientific quality of a study

Coordinator must be written by coordinator they should get IRB protocol to have: step-by-step
instructions per IRB protocol, helps guarantee standard tasks, ensures participants receive same
treatment

Recommended elements:

 Purpose
 Methods and procedures
 Clarification of terminology
 Required equipment and supplies
 Credentials and training required
 Plan for quality control

Journals commonly require research teams to address how a staff was trained to carry out a
treatment. Well-written SOPs make this process much easier

Treatment fidelity

Is a commitment that you have a plan and are sticking to it, ensures consisten treatment, per the
IRB protocol, for every participant by recording interactions each day for each participant, don’t
play favorites, asking questions to enure understanding, use daily notes

Track data back to its source to ensure quality data

Importance of treatment fidelity has grown, fidelity specifics required for journals and research
sponsors and usually some use entire SOP dedicated to fidelity measurement and maintenance

Protocol deviations

Can have associated adverse events

Devations range from missing survey pages to missed visits, well-written IRB protocols address the
unexpected

Use consistent reporting methods

How to minimize protocol deviations? Open communication among team members, appreciation
for the importance of recognizing and reporting deviations, learn from them
Deviations will show IRB protocol holes that you may have missed, make appropriate amendments
with the IRB throughout the study to minimize future deviations

Review and assessment

Recruitment and retention

Multi-pronged approach

Processes

Efforts to enroll and retain participants, participant qualifications are in the inclusion and exclusion
criteria of a clinical protocol, people who do not meet these criteria cannot participate

There must be diverse the population, a varied sample will ensure a realistic picture, funding
organization often require a diverse study sample, keep participants engaged in study without
pressuring

Strategies

Strategies for recruiting participants should be appropriate for the population you are targeting,
use multiple recruitment strategies, ask peers for advice, all recruitment strategies and materials
must be approved by the IRB before you use them

 Print
o Letters, Flyers, Brochures, Newspapers ads
o How is the content presented? Easy to understand, accurate, call to action, eye-
catching
 Online
o Social media, websites (advocacy groups, lab website, clinicaltrials.gov)
o Search engine advertising
 In-Person
o go where the people are, advocacy groups, community events, promotional items,
clinics
 Don’t
o Never coerce, never pressure, compensation must reflect time and effort, never
make promises, make sure graphics and images are appropriate

Retention strategies

Tailor these to your participants, use more than one method

- Build trust
o Get to know someone, communicate openly, provide clear materials, answer
questions honestly, do what you say, make study visits convenient and enjoyable,
share outcome results with IRB approval
- Check-in
 o Interact with participants, ask questions, let them know you’ll be in contact,
gather contact information (2 phone numbers or email), ask if its okay to leave a
voice mail, follow your institution policy on email use
- Be social
o Start with small talk, send thank you cards or periodic study newsletters
- Don’t
o Never coerce, never pressure

Considerations

Ethical considerations

- It is unethical to coerce a participant by promising them a cure or treatment, emphasize

that study participation Is research, participants should never feel pressured

Cultural, ethnic, racial considerations

- Know your audience, be sensitive to cultural, racial, and ethnic backgrounds

Characteristics of the recruitment setting

- Consider the setting, privacy needs to be protected, be aware of the potential participants
current situation

IRB approval

- All materials and methods must be approved by the IRB, check with your institution for
help

Plan if a participant drops out

- Have a plan in place if a participant drops out, will you need to recruit another participant
to replace the one who dropped out? How will their data be handled moving forward?

How did you hear about us?

- During a visit, ask participants how they heard about your study, can collect information
and re-target your efforts

Informed consent communication and process

Ensure participants know what is going to happen within a study

Re-consent if there are changes

A social and behavioral research study is research, not treatment

Participants must understand what they are signing up for

Review entire informed consent document with participants before beginning the study

Consent form template provided by IRB, principal investigator or research assistant will complete
this document, sixth to eighth grade reading level, contact your IRB for answers
Introduction: voluntary nature of research, study title, names and credentials

Purpose: study goals

Qualifications to participate: eligibility and exclusion criteria

Design and duration of study: expectations, procedures, assessments, and time frames, use ranges
in numerical descriptions, explain data collection, storage, destruction

Voluntary participation: emphasize voluntary nature of participation, explain how to withdraw

Alternative treatments: what are other options available

Possible risks and discomforts: detail any expected risks and discomforts and how to minimize
their occurrence

Benefits: explain the benefits of participating in the study, money is not a study benefit

Compensation: explain any financial compensation or responsibility

Policy regarding research related injuries: how do participants report illness, injury, or other
problems

Confidentiality: who has access to their data? How is data protected?

Contact information: address, phone numbers, email addresses, contact information for the IRB

Upon IRB approval, prepare for first participant visit, explain every element, give participants time
to review informed consent document ahead of time, practice, ideal room is private and quiet, tale
every precaution possible to ensure privacy

Participant conversations

Subsequent visits

Remind participants what they will be doing, answer questions, confirm continuation of study,
depending on study and IRB policies, re-consent may be needed

Other considerations:

- Vulnerable populations: especial regulations like children, teenagers, congnitively

impaired individuals, prisoners, and pregnant women, regulations provide additional
protections, but may affect consent process and document, check with IRB
- Consent vs assent: consent forms are signed by adults over 18, assent allows minos to
make their own decision, multiple assent forms for study are acceptable, depending on
participant age
- Coercion and compensation: coercion can come from family members, friends, faculty
advisors, professors and healthcare providers
- Violations: implement procedures to ensure most current document is used, print consent
forms as needed, must obstainsignature prior to study, never sign or date a consent form
for a participant
Privacy and confidenciality

Privacy: individuals right to control information about themselves

May be physical, biological, behavioral or psychosocial information

Protect participants privacy

- Are interviws in a private room? Speak in a quiet voice, have other been asked to leave?,
are you protecting sensitive information?

Confidentiality (their data): extention of privacy

Refers to how information is kept: who can see it, who handles it? Anything identifiable that can
be linked to a participant

Protection strategies

 Recruitment
o Be aware of your surrandings, find a private space, contact with participants must
be respectful
 HIPAA requirements
o Requires the protection and confidential handling of protectec health information
 Focus groups
o Remind participants the setting is not private, what happens in the focus group is
private and stays there
 Site selection
o Consider meeting sites carefully, provide a safe environment
 Site outside the clinic
o Plan ahead to protect privacy, maintain confidenciality with data, check your
institutions policy
 Home visitation
o Ask non-participants to leave the room, ensure participant is comfortable
 Communication
o Digital information gathering presents risks, protect digital identity
 Group intervention
o Remove all references to identifying data, what happens in the group stays within
the group
 Data collection
o Inform participants how and when data are collected, unless you have
specificapproval from the IRB, do not collect data before the inform consent
process
 Data security
o Use only approved portable storage devices, lock file cabinets and password
protect computers, follow your institution policies for proper and secure data
storage, store identifying data in separate location from other collected data
 Data sharing
 oMake a plan for who access to data, develop a data use agreement, gain the
approval from your IRB for any data sharing
 Password protection
o Protect all computers and devices with access to study data
o Check with your IT department for a secure server
 Study team access
o Only IRB-approved team members should have access to indentifiable data,
including: PI, coordinator, research assistant, update your lists and controls to who
has access
 Electronic Backup
o Never store identifiable data on non-secure device, contact your IT department on
approved secure storage locations
 Recording restriccions
o Video and audio recording restriccions, lay out recorded data storage plan in IRB
protocol and informed consent document, make participants aware of any
recordings, never include identifiable data in transcrips of recordings
 Transcriptions
o Remove all names, use alphanumers codes, store direct identifiers and code list in
separate locations
 Certificates of confidentiality
o Protect against forced disclosure of: substance abuse, illegal beahviors, sexual
attitudes, orientation, or practices, genetic information, psychological well-being

Documenting and reporting

Plan for potential breaches, begin with detailed plan that has been communicated with team
members, report the breach: manner in wich it occurred, how it was discoverded, extent of
breach, any breach is considered reportable

Participant safety and adverse event reporting

Intoward medical occurrence

May or may not be caused by treatment

Is the event unexpected? Is the event related to the research participation? Does the event put
participants or others at greater risk of harm?

IRB protocol should list potential risks, define what an adverse event is at the begingin of study,
definition must be consistent with institutional guidelines, approved by IRB

Clasified by:

- Seriousness
o Death, life threatiening circumstances, long term hospitalization or disability
- Relatedness
o Possibly related to a participants involvement in a study
- Expectedness
 o Already observed or outlined in IRB protocol

Include:

 Date
 Expected or unexpected
 Relation to study
 Event description
 Steps to address events
 Include resolution

Data safety monitoring boards, it’s a collection of people who monitor data

Details how participant safety and data integrity are observed

Independent experts, recuited by PI or sponsor

Looking for trends, violations, study milestones

If trends of Adverse events: clinical protocol changes

Quality control and assurance

Quality assurance: planned and systematic actions established to ensure that the trial is
performed and the data are generated, documented, and reported in compliance with GCP and
the applicable regulatory requirements

Quality control: operational techniques and activities undertaken within the quality assurance
system to verify the requirement for the quality of the trial-related activities have been fulfilled

Random error: occurs in all reseach studies and measurements, due to implicit and unpredictable
variations, design should minimize random errors, variability in the participant sample, cannot be
controlled or predicted by a study team

Systematic error: every data point is exposed to the same set of errant circumstances, related to
imprecise calibration or differences in observations and measurement, can be mitigated with
calibrating processes and continual education, participants may be characteristically different

Influence of time: highest priority participant safety, collecting good data comes second

Transcription errors

Strategies to avoid quality pitfalls?

Research misconduct

Research misconduct: fabrication, falsification, or plagiarism in proposing, performing, or

reviewing research, or in reporting research results, doesn’t include genuine error or different
opinions

Fabrication: making up data or results

Falsification: manipulating materials, equipment, or processes

Plagiarism: borrowing or stealing ideas, methods, results of another person without permission or
citation

Intent: intent to deveive is important, act must be committed intentionally, knowingly or recklessly

Consequences on research team:

- Damaged credibility
- Reassignment
- Loss of employment
- Barred from doing research
- Suspension or modification of an award
- Recovery of funds
- Name on NIH misconduct list ORI.hhs.gov
1. Understand the situation, maybe honest error
2. Bring it to someone you trust
3. Report up the chain

Prevent misconduct

Discuss issues openly, hold regular meetings, record location of reseach data files, quality control
and quality assurance: doble data entry, secondary data review

Conclusion/wrap-up