Guide to the Institutional Review Board for Kaiser Permanente Southern California

      What is the Institutional Review Board?

The Institutional Review Board (also known as IRB) is charged with protecting the rights and welfare of people involved in research. The IRB reviews plans for research that involve human subjects. All institutions that accept research funds from the federal government must have an IRB review all research that involves human subjects, even if the research project does not involve federal funds. This review is a federal legal requirement, not a requirement of Kaiser Permanente.

The definition of research involving human subjects is broad. The IRB must review research that involves review of medical and administrative records, research that uses left-over tissue, health services research, survey research, and behavioral research, as well as biomedical and other clinical research.

      Why does Kaiser Permanente Southern California require research to be reviewed and
      approved by the IRB?  

Review of research involving human subjects is required by federal law. It is NOT a local Kaiser Permanente Southern California (KPSC) requirement. It is federally mandated. The federal laws and regulations are very detailed and specific about what the IRB must do in order to comply with these laws and to protect human subjects.

The federal requirement for review of research by an IRB stems directly from experiences of the Tuskegee Study. The Tuskegee Study was federally funded. In it, a large number of poor black men with syphilis were studied for several decades to determine the natural history of untreated syphilis. The diagnosis of syphilis was made before treatment for the disease was available, but the men were not offered treatment with penicillin even after it became available. Worse, the men were not told that they were subjects in a research study. Many men in the study died of the complications of syphilis.

When this breach of ethics became publicly known in the middle 1970s, the federal government decided to put in place legal requirements for an external process for review and approval of research done using federal funds. The federal government also decided to require that all institutions accepting federal research funds review all research done in that institution by the same procedures. KPSC accepts federal research funds, and thus the IRB must review all research done here.  Top

      What is research?

Federal regulations define “research” as:
“…a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.”

Studies that involve patient interviews, follow-up contact of patients to determine the effectiveness of a program or a treatment, chart review, analysis of computer-stored clinical and administrative data, and mailed questionnaires, as well as randomized trials of experimental drugs, devices, and procedures must be reviewed and approved by the IRB because there is contribution to generalizable knowledge.

Marketing surveys and surveys to assess patient satisfaction do not require IRB review and approval because contracts with member groups specifically allow members to be contacted without such approval and because these surveys do not contribute to generalizable knowledge. Surveys of utilization and quality of care do not require IRB review and approval if the purpose of obtaining the information is to guide marketing decisions and to help make decisions about how to improve the quality of care. However, chart review and analysis of clinical information system done to assess quality of care do require review and approval by the IRB.

If information from a project will be published in a scientific journal or presented at a scientific meeting, the project is considered research by the federal definition and requires IRB review and approval. Publication or presentation implies an intention to contribute to generalizable knowledge. Additionally, many medical journals require documentation of review by an IRB as a condition of publication.

Any project that involves randomization of members to different interventions must be reviewed by the IRB, even if the project is a quality improvement project since random assignment is by definition an experiment and thus research.

The distinction between a quality improvement project such as a marketing survey and a research study can be blurry. If there is a question, please contact the IRB administrator for help in determining whether the project constitutes research and requires a review.  Top

      What does the IRB do?

The IRB reviews a written description of the study protocol and the researcher’s description of how the rights of human subjects will be protected. The IRB decides whether the benefits of the research outweigh the risks and whether the procedures for protecting subjects are adequate.

Some of the questions the IRB asks about the research include:

·         What is going to happen that would not otherwise be happening?

·         What is the researcher going to tell subjects about the research? Is this accurate?

·         Are there risks in what is going to be done? How big are those risks? What is being done to minimize those risks? What is the researcher planning to say to people about the risks? Is this accurate?

·         Are there any benefits to the individual participating in the research? What are those benefits? What is the researcher planning to say to people about the benefits? Is this accurate?

·         Will the research benefit society? How great are those benefits?

·         Do the societal and/or participant research benefits outweigh the risks?

      Who is on the IRB and how are members chosen?

Federal law dictates the composition of the IRB. The IRB must have at least six members. At least one member must be a lawyer and at least one member must be a representative of the community who is not affiliated with the institution. The IRB must be diverse in terms of ethnicity.

At the present time, the KPSC IRB has 13 members, including one alternate. The IRB consists of physicians, KP patients, lawyers, PhD researchers and non-KP affiliated members of the communities we serve.  Three members of the IRB are ethnic minorities.  Top

      What are the procedures for review?

There are three kinds of review: full committee review, expedited review, and administrative certification of exempt status. When a study undergoes full committee review, the entire IRB reviews it at the monthly IRB meeting. For purposes of expedited review, a subcommittee consists of one to three regular IRB members who provide their recommendations about approval of the study. This expedited review is done by mail. The IRB chair may delegate the verification of exempt status to board members or the IRB administrator.

      Full Committee Review

Studies that involve the use of experimental drugs or genetic testing, studies that involve interviews or surveys of members, and studies that involve external release of data undergo full committee review.

 

Process

A KPSC research application form must be filled out and submitted to the IRB administrator. Forms are available online or from the IRB office. The form describes the study protocol and how the rights and welfare of subjects in the study will be protected. Once an application is received, the IRB staff reviews it for completeness. If more information is required, it is requested.

Before the IRB reviews the application, the study protocol is sent to one or more board members for review. In addition, outside experts may be asked to review the scientific merit of the study and provide a written opinion about the study’s scientific value.

When all of the information necessary for the IRB to review the study has been received, it is put on the agenda for the IRB meeting.

The IRB meets once a month, on the third Tuesday of the month. Protocols for new projects must be received by IRB by 5 p.m. three weeks and four days before the scheduled meeting. Responses to queries by the IRB staff must be received no later than three business days following the deadline.

The IRB does one of the following based on its review:

·         Approves the study as it has been submitted.

·         Approves the study contingent on minor stipulations in the study protocol or for the protection of subjects.

·         Defers the study to obtain further information and/or clarification of the protocol and/or procedures for protecting subjects.

·         Disapproves the project for conduct in KPSC because the balance of risks and benefits is not appropriate, because subjects are not adequately protected, or because of concerns about conflicts of interest.

Timelines for Review

A new study must be submitted three weeks before the IRB meeting. If the study is approved exactly as submitted, a memo documenting approval is sent out approximately one week later. It takes about five weeks from the time of submission of the study to the IRB to notice of approval. If the IRB defers the study for more information, it usually is not considered again until the next meeting, increasing the time from submission to approval to ten weeks.

IRB approval will be faster if time is taken to consult with experts to be sure that everything that is needed by the IRB has been received. When research involves physical risks (for example, when an experimental drug will be used), it is worthwhile to get opinions from others about the procedures for minimizing risks.  Top

      Expedited Review

Studies that involve no risk or minimal risk can use the expedited review process. Appendix 1 describes the kinds of research that federal law has defined as having no risk or minimal risk. Chart review studies, studies that use existing biologic specimens but do not involve genetic testing, and studies that use only computer-stored data that is not released externally generally fall in this category.

Process

A KPSC research application form must be filled out and submitted to the IRB administrator. Forms are available online or from the IRB office. The form describes the study protocol and how the rights and welfare of subjects in the study will be protected. Once a completed form is received, the IRB staff reviews it for completeness. If more information is required, it is requested.

The IRB staff sends the protocol to the IRB subcommittee. The subcommittee consists of one to three members of the regular IRB. The subcommittee members review the protocol without meeting in person. They provide their recommendation about approval by mailed ballot.

The subcommittee does one of the following:

·         Approves the study.

·         Approves the study contingent on changes in the study procedures and/or consent process.

·         Defers the study for further information and/or clarification of the protocol and/or procedures for protection of subject.

·         Refers the study for full committee review.

The IRB subcommittee does not disapprove studies. Studies that the subcommittee believes should be disapproved are submitted to the full committee for a decision.

Timeline for Review

Studies can be submitted for expedited review at any time. They are sent out for review within five days of being received, if they are complete. Expedited review usually takes less than two months. Delays occur if the study needs full committee review.

      Request for Exemption

Some research studies are exempt from IRB review. Studies that are exempt include surveys that are anonymous (the person cannot be identified at all), studies in educational settings, and studies of leftover tissue when a person cannot be identified. A special form, the Request for Exemption for KPSC IRB Review and Determination of Privacy Rule Requirements, is filled out to request an exemption from IRB review. KPSC will not provide a retrospective verification of exemption from KPSC IRB review to research that has already been conducted.

Determination of Privacy Rule Requirements. The KPSC IRB will follow applicable federal regulations (The Privacy Rule) when determining if research that is exempt from KPSC IRB review requires written authorization to use and/or disclose PHI or whether the research qualifies for a waiver or alteration of such authorization.  Top

      Does the IRB require written consent for all research?

A requirement for IRB review is not the same as a requirement for written consent. Many studies, including chart review studies, most surveys and questionnaires, and the analysis of computer-stored data, do not require written consent, although they do require IRB review and approval.

To protect human subjects, it is essential that people freely decide whether they will be subjects in research after having the research and its risks and benefits explained. Not all studies require written consent but consent to be a research subject is important in all studies.

      Consent Procedure for Surveys and Questionnaires

The requirement for consent of people who participate in telephone surveys or fill out questionnaires can usually be satisfied by providing the subject with the information about the study in the form of a “script” that is read to them when they are contacted, in a cover letter sent with the questionnaire, or in a printed box at the top of the questionnaire. The following information must be provided so that the person who is being asked to be in the study can make an informed decision about whether or not s/he wants to be a participant:

·         A statement that the study is research.

·         A description of the purpose of the study.

·         The name of the person doing the study.

·         The reason why the person is being asked to participate.

·         What they are being asked to do.

·         A description of the risks and benefits of participating, if there are any.

·         A statement that they do not have to participate and that a decision not to participate will not affect their medical care.

When a person is being asked to participate in a study because s/he has an illness, the IRB may require attending physician permission to contact the patient. This permission can often be obtained in the form of departmental or administrative approval to enroll all patients in a certain category rather than by permission of individual physicians.  Top

      Studies That Require Written Consent

When a study involves “more than minimal risk,” the federal regulations require written consent. That is, the subject must read and sign a research consent form. A surgical consent form, even if it is a written consent form, cannot be substituted for a research consent form.

A study involves “more than minimal risk” when it does not fall into one of the categories of research that is considered to involve no risk or minimal risk. Studies that do not fall into one of the categories on this list require the research subject’s written consent.

When written consent is required, the consent must include (but may not be limited to) the following:

·         A statement that the study involves research, an explanation of the purposes of the research and the expected duration of participation, a description of the procedures to be followed, and identification of any procedures that are experimental.

·         A description of risks or discomforts to the subject.

·         A description of benefits.

·         A description of alternative procedures or courses of treatment.

·         A statement describing the extent, if any, to which confidentiality of records will be maintained.

·         An explanation of whether any compensation or treatment will be available if injury occurs, and if so, what it consists of and where further information can be obtained.

·         Who to contact for answers to questions related to the research and who to contact if a research-related injury occurs.

·         Statements that participation is voluntary, that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and that the subject may discontinue participation at any time.

KPSC researchers are asked to submit a draft of the consent form they would like to use. Consent forms that are approved by the IRB are re-drafted by the Southern California Permanente Medical Group (SCPMG) Legal Department so that the wording of each of the sections is standard.

      Does research require continuing (annual) review?

Federal law requires the IRB to do continuing review not less than every year. At the time of annual review, the IRB must make a decision whether the balance of risks and benefits remains reasonable and whether any changes to the study protocol or the procedures for protecting subjects need to be made.

The IRB will withdraw its approval if the researcher does not provide the information that is needed to decide whether or not to continue its approval. Research must cease if the IRB withdraws its approval. This is a federal requirement.

      What about studies approved by other IRBs?

All research studies that involve KPSC members and/or staff must be reviewed and approved by the KPSC IRB, even if they have been reviewed and approved by another IRB. A study that has been reviewed by other Kaiser Permanente IRBs must also be reviewed by the Southern California IRB if Southern California members, records, or data will be involved.

Occasionally someone from outside KPSC will ask if they can tell members about studies that are being done somewhere else by putting out an informational brochure or putting up posters in waiting rooms. These requests should be referred to the KPSC IRB, where the IRB will review them and take one of the following actions:

·         Approve the placement of informational material in the waiting room.

·         Disapprove the placement of informational material in the waiting room.

·         Require the study to undergo full committee review.

When a study involves direct solicitation of research participants through a phone contact or a letter, the study must undergo full KPSC IRB review.  Top

      Why does the IRB require a special application form?

Many studies submitted to the KPSC IRB have been reviewed by other IRBs or have been submitted to other agencies for funding or approval. Researchers often ask if they can submit their study proposal in these formats rather than describing the study on the KPSC IRB research application form.

The KPSC IRB requires studies on its own research application form for two reasons. First, outside applications are often very long, sometimes hundreds of pages. Every month, IRB members review 10 to 15 new proposals which they receive one week prior to the KPSC IRB meeting. It becomes extremely difficult and time-consuming for KPSC IRB members to read applications when they are long.

Second, the information that the KPSC IRB needs to make decisions about the balance of risk and benefit may appear in many different places on other applications and may be very hard to locate, especially when the protocol is long. In some cases, outside protocols do not have information required by the KPSC IRB (e.g., a description of risks, benefits, and alternatives).

      Research that Federal Law Defines as Having No Risk or Minimal Risk

Collection of hair and nail clippings, in a non-disfiguring manner, deciduous teeth, and permanent teeth if patient care indicates a need for extraction.

Collection of excreta and external secretions including sweat, uncannulated saliva, placenta removed at delivery, and amniotic fluid at the time of rupture of the membrane prior to or during labor.

Recording of data from subjects 18 years of age or older using non-invasive procedures routinely employed in clinical practice. This includes the use of physical sensors that are applied either to the surface of the body or at a distance, and do not involve input of matter or significant amounts of energy into the subject or an invasion of the subject’s privacy. It also includes such procedures as weighing, testing sensory acuity, electrocardiography, electro-encephalography, thermography, detection of naturally-occurring radioactivity, diagnostic echography and electroretinography. It does not include exposure to electromagnetic radiation outside the visible range (for example, x-rays, microwaves).

Collection of blood samples by venipuncture, in amounts not exceeding 450 milliliters in an eight-week period and no more often than two times per week, from subjects 18 years or older who are in good health and not pregnant.

Collection of both supra- and subgingival dental plaque and calculus, provided the procedure is not more invasive than routine prophylactic scaling of the teeth, and the process is accomplished in accordance with accepted prophylactic techniques.

Voice recordings made for research purposes, such as investigations of speech defects.

Moderate exercise by healthy volunteers.

The study of existing data, documents, or records. The study of pathological specimens, or diagnostic specimens, except when this involves identification of genotype affecting disease risk.

Research on individual or group behavior or characteristics of individuals, such as studies of perception, cognition, game theory, or test development, where the investigator does not manipulate subjects’ behavior and the research will not involve stress to subjects.

Research on drugs or devices for which an investigational new drug exemption ( IND ) or an investigational new device exemption (IDE) is not required (except if there is randomization).

Research involving survey or interview procedures, except where all of the following conditions exist:

·         Responses are recorded in such a manner that the human subjects can be identified, directly or through identifiers linked to the subjects.

·         The subject’s responses, if they become known outside the research, could reasonably place the subject at risk of criminal or civil liability or be damaging to the subject’s financial standing or employability.

·         The research deals with sensitive aspects of the subject’s own behavior, such as illegal conduct, drug use, sexual behavior, or use of alcohol.

      Research that Federal Law Defines as Exempt

Research that is conducted in established or commonly accepted educational settings, involving normal education practices, such as:

·         Research on regular and special education instructional strategies.

·         Research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

Research that involves the use of education tests (cognitive, diagnostic, aptitude, achievement), if information taken from these sources is recorded in such a manner that subjects cannot be identified directly or through identifiers linked to the subjects.

Research that involves survey or interview procedures, when the respondents are elected or appointed officials or candidates for public office.

Research that involves observation (including observation by participants of public behavior) except where any of the following conditions exist:

·         Observations are recorded in such a manner that the human subjects can be identified, directly or through identifiers linked to the subjects.

·         The observations recorded about the individual, if they became known outside the research, could reasonably place the subject at risk of criminal or civil liability or be damaging to the subject’s financial standing or employability.

·         The research deals with sensitive aspects of the subjects’ own behavior, such as illegal conduct, drug use, sexual behavior, or use of alcohol.

Research that involves the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.

                                                                               

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