Understanding Research: Getting Your Project Ready for the IRB

1
Understanding Research Getting Your Project
Ready for the IRB

• Jill Stoltzfus, Ph.D.
• Director, Research Institute
• stoltzj_at_slhn.org

2
Todays Objectives

• Present the general purpose and (very brief)
  historical background of the Institutional Review
  Board (IRB).
• Determine which types of research require IRB
  approval at St. Lukes.
• Explore the IRBs roles and responsibilities.
• Your turn Preparing your research for the IRB
  review process.
• Q A
• Wrap up

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What is the IRB, and Where Did it Come From?

• The IRBs sole purpose is to protect people who
  are enrolled in clinical research.
• The concept of the IRB came from the Declaration
  of Helsinki document in 1964, which set up an
  international standard for biomedical research
  with human subjects.
• Prior to this, federal guidelines for conducting
  medical research in the United States only
  applied to research at the National Institute of
  Health (NIH).

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The Uglier Side of Research Over the Years

• Thalidomide Experience (1950s) Women were
  routinely given thalidomide as an investigational
  drug to help them cope with pregnancy symptoms,
  but severe growth deformities started occurring
  in infants as a result. Unfortunately, these
  women were never fully informed about the
  experimental nature of thalidomide and the fact
  that it was still in the testing phase.
• Willowbrook Hepatitis Studies (1950s) In order
  to see which factors might lead to hepatitis
  transmission, mentally retarded children living
  in a long-term care facility in New York were fed
  a concoction containing feces from children with
  active hepatitis.

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The Uglier Side of Research Over the Years

• Jewish Chronic Disease Hospital Studies (1960s)
  In order to see how a compromised immune system
  might influence the spread of cancer, researchers
  injected live cancer cells into demented patients
  at a chronic disease hospital in New York City.
• San Antonio Contraception Study (early 1970s)
  Poor, indigent patients from a contraception
  clinic in Texas were given either contraception
  or a placebo without being told they were in a
  research study or that they might be getting
  inactive birth control.
• Tearoom Trade Study (early 1970s) A social
  scientist named Laud Humphries wanted to study
  homosexual behavior in public settings, so he
  spent time at public restrooms watching people
  engage in anonymous sex. Then he recorded their
  license numbers and used this information to
  track them down and interview them about their
  background and family life. He eventually
  published his findings.

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The Uglier Side of Research Over the Years

• Miligram Studies of Obedience to Authority
  (1960s) In order to determine why people obey
  authority figures even when asked to perform
  cruel acts, psychologist Stanley Miligram
  recruited people to read word pairs to people
  sitting out of sight behind a wall, then to
  deliver increasing shocks each time a wrong
  answer was given, from 45 to 450 volts. A hired
  actor screamed and complained about his heart
  condition as the shocks increased in intensity.
• Despite the discomfort expressed by several
  participants at delivering these shocks, 65 of
  them delivered what they thought was the maximum
  of 450 volts.
• When this study was repeated in other settings
  and other countries, between 61-66 of people
  responded in the same way!

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The Uglier Side of Research Over the Years

• Tuskegee Syphillis Study (1932 - 1972) In order
  to determine the effects of untreated syphillis
  on the human body, the U.S. Public Health Service
  observed poor, uneducated black sharecroppers in
  the rural South over a four-decade period.
• Participants were never told about the nature of
  this research, nor did they fully understand
  their disease state. Additionally, they thought
  they were getting good medical care due to the
  many tests and procedures to which they were
  subjected.
• One negative long-term effect of this study has
  been the reluctance of many black people to
  participate in research given their suspicions
  about whether they are being experimented upon
  in similar fashion to the men in the Tuskegee
  study.

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Who Sets the Rules and Regulations for IRBs?

• Two organizations within the Department of Health
  and Human Services (HHS) are most influential in
  deciding what IRBs must do
• Food and Drug Administration (FDA) Applies to
  research involving all products regulated by the
  FDA.
• Office for Protection from Research Risks OPRR)
  Applies to research involving human subjects that
  is conducted or funded in any way by HHS.
• In addition, individual institutions may (and
  often do) have their own rules and regulations.

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Which Types of Research Require IRB Approval at
St. Lukes?

• Some institutions have different types of IRB
  review procedures depending on the nature of the
  research study (e.g., full review for more
  intrusive or potentially harmful studies
  expedited review for minimal risk studies.)
• However, at St. Lukes, all research proposals
  must first go through the IRB to determine
  whether they require full review or can be
  exempted--even the projects that seem relatively
  harmless (e.g., a retrospective chart review).
• Once this happens, the IRB committee sends you
  either a letter indicating the need for full
  review or a letter of exemption from full review.

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Who Serves on the IRB?

• The Department of Health and Human Services (HHS)
  requires IRBs to have at least 5 members to
  ensure adequate review of all research projects
  and proposals
• There must be at least one non-scientist (e.g.,
  attorney, clergy member)
• There must be at least one person who isnt
  affiliated with the institution or isnt an
  immediate family member of someone affiliated
  with the institution.
• Ideally, there should be a diverse mixture of
  members from different racial/ethnic, gender,
  cultural and community backgrounds.
• Any IRB member with a conflict of interest
  (meaning a financial or other stake in the
  research) is excluded from reviewing that
  particular research proposal.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Risk/benefit analysis
• Informed consent
• Selection of subjects
• Privacy and confidentiality
• Monitoring and observation
• Safeguards
• Incentives for participation
• Continuing review
• Record keeping

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Risk/benefit analysis
• Is there a high likelihood of physical,
  psychological, social or economic harm/injury
  that might result from participating in a
  research study?
• Physical harm Pain, discomfort or injury due to
  medical procedures or possible side effects of
  medication.
• Psychological harm Depression, confusion,
  hallucinations or other negative changes in
  emotions and thought processes.
• Social and economic harm Criminal prosecution,
  being humiliated, loss of employment or other
  negative outcomes due to being labeled as sick.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Risk/benefit analysis
• Are the risks no greater than what you might
  experience in daily life or during a routine
  checkup?
• Example of acceptable risk Drawing blood from
  healthy study participants (since this could
  happen during a regular medical appointment.)
• Example of a risk with possible problems Denying
  potentially effective treatment to participants
  in the placebo group of a randomized control
  trial.
• Example of a situation where greater risk might
  be allowed Testing a new drug for a
  life-threatening condition (such as metastatic
  cancer).

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Risk/benefit analysis
• Is the desired outcome in balance with the
  potential risks?
• Will the study investigator be able to carry out
  the research with a high level of competence?
• Are there adequate safeguards in place to protect
  participants (with special protection for more
  vulnerable populations such as fetuses, pregnant
  women, children and prisoners)?
• Will study procedures and practices be monitored
  on a frequent basis?
• The perception of some risks might be subjective,
  depending on the participant (e.g., hair loss as
  a side effect might be viewed differently by a
  teenager than by a 75-year-old man.)

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Risk/benefit analysis
• Are the benefits likely to improve participants
  quality of life and increase the medical fields
  knowledge in concrete ways?
• In other words, is this study worth the time,
  energy and effort to even bother conducting in
  the first place????

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Informed consent
• The big question Have participants been
  adequately informed about what theyre getting
  themselves into BEFORE the study begins?
• Interesting historical tidbit Informed consent
  has its roots in the Nuremburg Code of post-WWII,
  when Nazi physicians were tried for the
  experiments they performed on concentration camp
  inmates (who obviously did NOT give their
  informed consent beforehand!)

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Informed consent Required components
• Statement saying that the study is indeed
  research.
• Detailed explanation about the research and
  participants roles and responsibilities.
• Expected length of the study.
• Projected benefits and possible risks.
• Presentation of any alternative treatments or
  approaches (even those that might be better than
  whats in the current study).
• Any limitations to privacy and confidentiality
  (e.g., who has access to research records.)
• Provisions in case of injury during the study
• Statement that participation is voluntary and can
  be ended at any time.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Informed consent Additional (but not required)
  components
• Statement about unforeseeable risks that might
  occur along the way.
• Situations in which participants involvement
  might be ended without the participants consent
  (e.g., unethical or dangerous participant
  behaviors).
• Extra costs that might arise as the study
  progresses.
• The number of participants in the study.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Informed consent How does it work?
• Once participants sign the form (or their legal
  representative does so), they must receive a
  copy.
• Any oral presentations about the informed consent
  process must be witnessed by a third person who
  then signs both the consent form and a copy of
  the written summary of the presentation.
• When can informed consent be waived?
• Research involving minimal risk (e.g., the only
  real risk to participants is a possible breach of
  confidentiality.)
• Emergency situations.
• If participants rights wont be adversely
  impacted.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Selection of subjects
• The big question Is the chance to participate
  both fair and equitable? Not always the case in
  past years
• In the 19th and early 20th centuries, poor
  patients in hospital wards were usually chosen
  for research studies, with little to no
  protection or recourse if something went wrong.
• During the Tuskegee trials (1932 - 1972),
  low-income black sharecroppers were enrolled to
  track the effects of untreated syphilis on the
  human body, but these participants werent even
  told they had the disease, and they werent given
  the option of being treated once penicillin was
  discovered.
• As a result of these historical blunders, IRBs
  are now supposed to determine whether certain
  groups (e.g., racial/ethnic minorities,
  low-income people) are being selected for the
  wrong reasons.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Selection of subjects
• Other situations IRBs need to consider regarding
  whether subjects are being selected fairly and
  equitably
• If students (e.g., the ubiquitous Psych 101
  college class) or military personnel are
  available for studies, will they be led to
  believe that their grades or performance reviews
  depend on their participation?
• If employees are available for studies, might
  they feel undue pressure to participate, lest
  they be passed over for raises?
• Are institutionalized persons or prisoners told
  that their participation will make things better
  for them or possibly reduce their length of stay?

22
What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Selection of subjects
• At the same time, researchers shouldnt go out of
  their way to exclude people from participating.
• IRBs must not overprotect vulnerable populations
  from participating if they really want to
  (although they should carefully consider things
  like discomfort, inconvenience and potential
  embarrassment for these populations.)
• IRBs need to consider how subjects are being
  recruited to make sure people from diverse
  backgrounds have an equal chance of getting
  selected for a study.
• In fact, if women and racial/ethnic minority
  populations arent being represented
  proportionately in a study, the researcher should
  give a very good reason why this is so.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Privacy and confidentiality
• The big question Does the research adequately
  protect participants personal information?
• For research on preexisting data (like chart
  reviews) Contact people to ask their permission
  to review records for a new study let people
  know ahead of time that their records may be used
  for future research substitute codes for names
  and store research documents in locked cabinets.
• For observational research In general, IRB
  review is only needed if a) minors are involved
  b) the studys observations can be directly
  linked to participants (e.g., through social
  security numbers) c) the observations may harm
  participants reputation or financial standing
  and d) the observations put participants at risk
  of civil or criminal liability.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Monitoring and observation
• The big question Does the research plan include
  a specific description of how data will be
  collected, monitored and analyzed?
• This is critical to ensure that the overall risk
  to participants doesnt increase as time passes,
  and that the research is therefore worth
  continuing.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Safeguards
• The big question If the research involves
  certain populations (e.g., children, pregnant
  women, prisoners) that may be vulnerable to
  coercion or undue influence, have special efforts
  been made to protect these participants rights
  and overall well being?
• This could include getting the co-consent of
  parents, relatives or neutral third parties.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Incentives for participation
• The big question If any rewards are offered for
  study participation, are they given in good
  faith?
• Currently, there are no federal guidelines for
  evaluating incentives within the context of a
  research study.
• Rewards should not be used to pressure
  participants to remain in the study if they dont
  wish to do so.
• Rewards can also become a problem if they prompt
  participants to lie, conceal information or
  engage in other unethical behaviors simply to get
  the reward.
• Some rewards (e.g., access to free medical care)
  may introduce selection bias if only certain
  people (e.g., those with low incomes) choose to
  participate in the study.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Continuing review
• The big question Once a research study gets the
  initial IRB stamp of approval, it must continue
  to be followed up through a structured review
  process.
• At the initial review, the IRB committee decides
  how often to conduct the follow-up reviews
  (usually dependent on the level of risk involved
  in the study.)
• Regardless of how many follow-up intervals are
  established, all research must be reviewed at
  least once annually.
• The initial IRB approval is only temporary and
  may be revoked at any time if problems arise over
  time. In fact, the IRB committee can require the
  study to be stopped completely if things get
  really bad.

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What are the Specific Roles and Responsibilities
of the IRB at St. Lukes?

• Record keeping
• Federal guidelines require all IRBs to keep the
  following records for at least three years after
  the research study is completed
• Progress reports of approved informed consent
  documents reviewed research proposals and
  reports of participant injuries
• Meeting minutes showing attendance and the number
  voting for, against and abstaining from research
  proposal decisions
• Records of all continuing review activities
• A comprehensive list of IRB committee members,
  including their names, earned degrees, licenses,
  role on the IRB committee, and any relationship
  with St. Lukes

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Your Turn How Do You Prepare for the IRB Review?

• Step 1 Make sure your research proposal is
  complete and well-organized before submitting it
  to the IRB.
• What is your research hypothesis--what are you
  trying to discover/prove/learn?
• How were participants selected, and how many are
  included? (Should have an accompanying power
  analysis to ensure a proper sample size--see me
  for this!)
• How do you propose to collect data? Are your data
  easily quantifiable/measurable?
• Are the potential risks and benefits to
  participants clearly given?
• What are your qualifications for conducting this
  research?
• If applicable, is your informed consent document
  written in easy-to-understand language? Is it
  thorough?

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Your Turn How Do You Prepare for the IRB Review?

• Step 2 Go to the IRB website (http//slhechowebsv
  r/manny/irb/irbframe.htm), where youll find
  everything you need to complete the application
  process, including
• A general description of the IRB, including when
  it meets (first Tuesday of each month) and the
  deadline for submission of research proposals
  (usually the 15th day of the preceding month).
• An overview of the research process at St.
  Lukes.
• A flowchart revealing how research is approved
  through the IRB.
• Links to frequently used policies and procedures
  (including the Initial IRB Application form,
  which is required for all St. Lukes research.)

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Your Turn How Do You Prepare for the IRB Review?

• NOTE If the previous link doesnt work, go to
• St. Lukes Intranet site (http//slhnweb/)
• Departments and Services link
• Bethlehem link
• Institutional Review Board link

32
Your Turn How Do You Prepare for the IRB Review?

• If you really believe your research study poses
  little to no risk to participants, you could
  first try getting an exemption from IRB review.
• Go to the Exemption of Research from IRB Review
  link in the St. Lukes Intranet site and follow
  the instructions (keeping in mind that your
  research must meet one of the following
  criteria)
• Is conducted in established educational settings.
• Focuses on the use of educational tests, surveys
  or observation of public behavior (with some
  exceptions).
• Involves the collection or study of existing data
  that is publicly available or recorded in a way
  that protects privacy.
• Examines public benefit or service programs.
• Addresses taste or food quality evaluation (with
  some exceptions).

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Your Turn How Do You Prepare for the IRB Review?

• Step 3 Wait to hear back (in writing) from the
  IRB committee about the status of your research
  proposal (meaning whether it requires full or
  expedited review).

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Summary of Steps to Prepare for IRB Review

• Step 1 Make sure your research proposal is
  complete, accurate and well-organized before
  submitting it to the IRB. If you need help with
  this, come see me.
• Step 2 Go to the IRB website (http//slhechowebsv
  r/manny/irb/irbframe.htm) to find all of the
  necessary forms, policies and procedures
  depending on the type of research you plan to
  conduct.
• Step 3 Wait to hear back (in writing) from the
  IRB committee about the status of your research
  proposal.

35
Q A

• Clarification of todays lecture points?
• Something more youd like to know?

36
Summary of Todays Objectives

• Presented the general purpose and (very brief)
  historical background of the Institutional Review
  Board (IRB)
• Determined which types of research require IRB
  approval
• Explored the IRBs roles and responsibilities
• Discussed how to adequately prepare for the IRB
  review process

37
Understanding Research Getting Your Project
Ready for the IRB

• Jill Stoltzfus, Ph.D.
• Director, Research Institute
• stoltzj_at_slhn.org