IRB operational doctrine

Weizmann Institute of Science

Human Subject Research Policy

  1. General
    1. All human subject research protocols must meet the Weizmann Institute of Science (“Weizmann”) ethical standards governing the conduct of research as described in this document, including acceptable risk-benefit relationship, equitable selection, informed consent, protections of privacy, maintenance of confidentiality, and protections for vulnerable populations.
    2. All research involving human subjects, human material or human data, which are performed at Weizmann, require the review and approval, or determination of exemption, by the Weizmann Institute’s Institutional Review Board – IRB (“Weizmann IRB” or “IRB”).
    3. Weizmann IRB role is to evaluate applications for research involving human subjects, samples, or data. Weizmann IRB also functions as the Embryonic Stem Cell Research Oversight (ESCRO) committee and evaluates applications for work with human stem cells according to the guidelines published by the US National Academy of Sciences.
    4. Current Israeli legislation - Public Health Regulations (Clinical Trials in Human Subjects) 1980  (“the Regulations”) apply to clinical trials in human subjects, which are conducted in a medical institution (‘Hospital’) and is silent about research involving human subjects, human material, or human data, performed in academic / research institutions.
    5. Weizmann has adopted a human subject research policy, based on the major principles of the Code of Federal Regulations Title 45 Public Welfare Department of Health and Human Services, Part 46 Protection of Human Subjects ("the Common Rule").
    6. Research involving human subjects, human material or human data may also require:
      1. An approval by an Helsinki committee of an Israeli medical institution (‘Hospital’) according to the Regulations. For example, if the material / data is obtained from patients undergoing medical treatment in a medical institution, or if the IRB determines that due to the nature of the research participants and / or procedures involved in the research protocol, a close medical monitoring is required. For review of such research protocols article 6 shall apply.
      2. An appropriate ethical approval of a collaborating research institution from which the human material or human data is obtained.
    7. Research which is supported by a US federal department or agency is subject to the Common Rule.
    8. Frequency of IRB Continuing Review
      1. Research protocols that involve no more than minimal risk may be approved by the IRB for a term of up to three years.
      2. For all other research protocols the IRB shall determine the period for continuing review.
      3. An exception to the time frames set in sections ‎1.8.1 and ‎1.8.2 are research protocols funded by US federal sources, which require continuing review by the IRB at intervals appropriate to the degree of risk, but not less than once per year.
  2. What Qualifies as Human Subject Research
    1. This Policy applies to Research Involving Human Subjects conducted at Weizmann by Principal Investigators and all their research team members.
    2. In order for a research to be considered as Research Involving Human Subjects , it must meet the following definitions:
      1. Research”: a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.
      2. Human subject”:  a living individual about whom a Principal Investigator and additional Investigators conducting research obtain data through intervention or interaction with the individual or identifiable private information. A subject may be either a healthy individual or a patient.
      3. Principal Investigator” / “Investigator”: Principal Investigator (‘PI’) is a scientist affiliated with one of Weizmann faculties. Investigator includes the Principal Investigator and any Feinberg Graduate School trainee (student, postdoc) or Weizmann personnel conducting research (hereinafter together: “Investigator”). The PI is the leader of the studies and is responsible for all ethical aspects of the research.
      4. Obtaining Data”: Receiving or accessing identifiable private information or identifiable specimens for research purposes. Obtaining is interpreted to include an Investigator’s use, study, or analysis for research purposes of identifiable private information or identifiable specimens already in the possession of the Investigator.
      5. Intervention”: Includes both physical procedures, by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes (including interviews and surveys).
      6. Interaction”: Includes communication or interpersonal contact between Investigator and subject (including online surveys).
      7. Identifiable Private Information”: Includes information, which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record, school grades, or height and weight measurements). It also includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place. Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the Investigator or associated with the information), in order for obtaining the information to constitute research involving human subjects. Examples of studies using private information include chart reviews, obtaining lab studies on identifiable tissues and specimens, or using identifiable information from data or tissue repositories, obtaining school grades, private interviews, or surveys of opinions and attitudes.
      8. Coded information”: Data or specimens are considered coded when identifying information that would enable the Investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain (e.g., name, social security number, etc.) has been replaced (e.g. ,by a number, letter, symbol, or combination thereof), and a key to decipher the code is required in order to enable linkage of the identifying information to the private information or specimens.
    3. The following activities are not considered to involve human subject(s):
      1. Cadaveric or autopsy specimens or data. Includes also autopsy specimens or data taken from live individuals who had deceased prior to the initiation of the research.
      2. Private data or specimens, which were not collected specifically for the currently proposed research through an intervention or interaction with living individuals AND given that the Investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain. For example, if information is coded and the Investigators enter into an agreement with the holder of the de-coding key, prohibiting the release of the key to the Investigators under any circumstances, until the individuals are deceased.
  3. Human Subjects Research Exempt from IRB Review 

    Research Involving Human Subjects may be exempt from IRB review if it 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 by the Investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects. This category includes specimen and data obtained from national and international bio-banks and repositories.

  4. Categories of Human Subjects Research Qualified for Expedited IRB Review
    1. General
      1. An expedited review procedure consists of a review of Research Involving Human Subjects by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB.
      2. In reviewing the research, the reviewers may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after full IRB review in accordance with the non-expedited procedure.
      3. The standard requirements for informed consent apply regardless of the type of review utilized by the IRB (expedited or full IRB review).
      4. Weizmann’s IRB members will be kept advised of research proposals which have been approved under the expedited procedure.
    2. Applicability
      1. Research activities that present no more than minimal risk to human subjects and involves only procedures listed in one or more of the categories listed in section ‎4.3 are eligible for expedited IRB review.
      2. “Minimal Risk” means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
      3. The activities listed in section ‎4.3 should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human subjects.
      4. Minimal changes in a research protocol previously approved by full IRB review, during the period for which approval is authorized (as detailed in section 1.8 above), may be reviewed by the IRB through the expedited review procedure.
    3. Research Categories Eligible for Expedited Review (both initial and continuing IRB review):
      1. Clinical studies of drugs / medical devices only when conditions (a) - (c) are met.
        1. The drug/medical device is cleared/approved for marketing.
        2. The use/application of the drug/medical device in accordance with its cleared/approved labeling imposes no more than minimal risk.
        3. The proposed use/application of the drug/medical device according to the research protocol imposes no more than minimal risk on the research subject.  

          For such studies the specialist performing a procedure should be an MD ,with appropriate training, whose specialty positions him well to make the relevant diagnosis, prescribe and follow up on usage of drugs / medical devices.

      2. Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture from healthy, non-pregnant adults, who weigh at least 50 Kg (110 pounds). The amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week.
        For such studies the specialist performing a procedure should be a practitioner meeting standards of care, approved by Israeli Ministry of Health to perform blood collection and holds the appropriate certificates. Often it will be (but not exclusive) MD.
      3. Prospective collection of biological specimens for research purposes by noninvasive means, not involving general anesthesia or sedation and by means routinely employed in clinical practice.

        Examples: (a) hair and nail clippings in a non-disfiguring manner; (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth if routine patient care indicates a need for extraction; (d) excreta and external secretions (including sweat); (e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax, or by applying a dilute citric solution to the tongue; (f) supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques; (g) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (h) sputum collected after saline mist nebulization; (i) nasal swabs that do not go beyond the nares.

        For minimally invasive dental procedures the specialist performing a procedure should be a practitioner meeting standards of care, approved by the Israeli Ministry of Health, holding the appropriate certificates. Often it will be (but not exclusive) DMD.

    4. Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing.
      Examples: (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject’s privacy; (b) weighing or testing sensory acuity; (c) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (d) moderate exercise, muscular strength testing, body composition assessment and flexibility testing, given appropriate considerations to the age, weight, and health of the individual.
    5. Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for non-research purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt IRB review under clause ‎3 above).
    6. Collection of data from voice, video, digital, or image recordings made for research purposes.
    7. Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies.
    8. Continuing review of research previously approved by full IRB review as follows:
      1. Where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects;
      2. Where no subjects have been enrolled and no additional risks have been identified;
      3. Where the remaining research activities are limited to data analysis.
  5.  Full IRB Review

    Research protocols detailed in sections ‎5.1  and / or ‎5.2 below, require full IRB review and sections ‎3 and ‎4 shall not apply to them:

    1. Research protocols which involve vulnerable populations, such as minors (age less than 18), prisoners, pregnant women, mentally disabled persons, dependent or legally non-competent individuals, or economically or educationally disadvantaged persons (“Vulnerable Populations”).
    2. Where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.
  6. IRB Review in Case of Hospital Helsinki Approval

    In cases of protocols approved by hospital Helsinki Committee the following shall apply:

    1. A protocol submitted with hospital Helsinki approval covers regulatory, ethics, and insurance aspects of the research. There will always be an MD principal investigator noted on file.
    2. The team members of the Weizmann research group will be added to the protocol if the research is tailored to promote a Weizmann study.
    3. Weizmann IRB will align local (WIS) approval expiry date to the Helsinki protocol expiry date.
    4. Some Helsinki protocols may be exposing participants to more than minimal risk, as hospital Helsinki committees find appropriate to approve.
    5. Weizmann IRB will check the Helsinki protocol under Expedited mode. This reveals proportionality, in adequately balancing several Weizmann interests (i) interest to monitor, (ii) acceptance of Helsinki competence and (iii) Weizmann interest to not be implicitly held responsible for legal aspects of the Helsinki decision.
    6. Weizmann IRB is authorized to reject an application to approve the study if it finds that the protocol raises legal or ethical concerns.
  7. Criteria for IRB Approval of Research

    In order to approve research covered by this policy the IRB must determine that all of the following requirements are satisfied:

    1. Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk; (ii) Whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes; (iii) Research activities are performed by an Investigator with specific training in the implemented procedures who is competent to handle expected adverse events.
    2. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.
    3. Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving Vulnerable Populations (as defined in section ‎5.1 above).
    4. Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with section ‎7 hereof.
    5. Informed consent will be appropriately documented, in accordance with section 7 hereof.  
    6. When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
    7. When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
    8. When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as Vulnerable Populations (as defined in section ‎5.1 above), additional safeguards should be included in the study to protect the rights and welfare of these subjects.
  8. General Requirements for Informed Consent
    1. No Investigator may involve a human being as a subject in research covered by this policy unless the Investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative.
    2. An Investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence.
    3. The information that is given to the subject or the representative shall be in language understandable to the subject or the representative. No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the Investigator, the sponsor, Weizmann or its agents from liability for negligence.
    4. Basic elements of informed consent
      In seeking informed consent the following information shall be provided to each subject, as applicable:
      1. A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;
      2. A description of any reasonably foreseeable risks or discomforts to the subject;
      3. A description of any benefits to the subject or to others which may reasonably be expected from the research;
      4. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
      5. An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and
      6. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.
    5. Additional elements of informed consent
      When appropriate, one or more of the following elements of information shall also be provided to each subject:
      1. A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;
      2. Anticipated circumstances under which the subject's participation may be terminated by the Investigator without regard to the subject's consent;
      3. The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;
      4. A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject;
      5. The approximate number of subjects involved in the study.
  9. Documentation of Informed Consent
    1. Informed consent shall be documented by (i) usage of a written consent form that embodies the elements of informed consent required by section ‎7 above (ii) approved by the IRB.
    2. A written consent document (i) shall be accompanied by comprehensive oral explanation by the Investigator. (ii) The Investigator shall give either the subject or the representative adequate opportunity to read it before it is signed. (iii) Document will be signed by the subject or the subject's legally authorized representative. (iv) A copy shall be given to the person signing the form.