Six Tips for Submitting a Clinical Study for Expedited Review

Tori-Picture-BlogExpedited review is a type of IRB review of research carried out by the IRB Chairperson or designee that is an experienced IRB member and reviewer rather than the convened IRB.[1] Expedited review is often an attractive alternative to submitting research for review by the convened IRB because at Quorum, this service has faster turnaround times than the standard review process, the submission process is simplified, and this service costs less than review by the convened IRB.

It is important to remember that research is only eligible for expedited review when specific criteria are met. This article is designed to provide practical guidance about when expedited review is an appropriate option for your research.[2] In the event expedited review is determined to be inappropriate for the research, it’s often a surprise and can cause frustration. Becoming familiar with the expedited requirements is a good way to ensure you can navigate the review process effectively.

Tip 1: Remember the Basic Requirements of Expedited Review

Under 45 CFR 46.110 and 21 CFR 56.110, expedited review of new studies is available for minimal risk research that involves listed study procedures published in the Federal Register. The Federal Register establishes that even if a study is minimal risk, if some study activities involve procedures that are not described in the categories, the research will not be eligible for expedited review. The list of expedited categories is identical for research subject to OHRP and FDA regulations.

Tip 2: Figure Out if Your Research is “Minimal Risk”
The first step to identifying whether the research is eligible for expedited review is making sure that it is “minimal risk”. Forty-five CFR 46.102(i) and 21 CFR 56.102(i) define “minimal risk” as “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.” One of the keys to figuring out if your research is minimal risk is to know that the minimal risk determination is indexed to experiences ordinarily encountered in the daily life of the average person rather than the population involved in the research. Also, research may not be considered minimal risk and is not considered eligible for expedited review, “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.” [3]

Examples:

  • A study is investigating the efficacy of an already approved drug to treat cancer, and meets the IND exemption requirements under 21 CFR 312.2(b). The study drug may have a more attractive risk profile than other therapies currently used as standard of care. However, the study drug still carries risks such as kidney damage, hair loss, nausea, and vomiting. Although the cancer patients enrolled in the study may actually experience fewer and less severe side effects than alternative treatments, and the risks posed by the study drug are ordinarily encountered by cancer patients seeking treatment, the study would not be considered minimal risk. The risks posed by the drug are not what average people encounter normally in everyday life – it would not be considered a typical experience for someone to be exposed to a drug designed to treat cancer in their everyday lives that could cause kidney damage, hair loss, nausea, and vomiting.

 

  • A study involves a survey of pregnant women primarily to ascertain information about their diets. The study also includes a review of the medical records related to the participant’s pregnancy, birth, and the birth outcomes of their child. In addition to questions about food, the survey asks the pregnant women about their use of alcohol, tobacco, marijuana, and other illegal drugs. The survey study will include the participant names and addresses. It is possible the expedited reviewer may determine this study does not meet the minimal risk definition because the responses could reasonably place the participants “at risk of criminal or civil liability or be damaging to the subjects financial standing, employability, insurability, reputation, or be stigmatizing.” Due to the sensitive nature of some questions on the survey, it may not be minimal risk under the standards for expedited review “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.”[4] If the researchers could find a way to collect the study data in an anonymized manner, it is more likely the study would be considered expeditable.

 

  • A study requires healthy participants to walk on a treadmill for four hours without a break. Although most healthy people could walk on a treadmill for four hours if needed, it is not something most normal healthy people would do in their daily life or experience as a routine physical exam or test. The experience would likely cause sufficient enough discomfort that this would not be considered minimal risk. Additionally, the procedure of walking on a treadmill for four hours does not qualify under one of the seven categories of expeditable study procedures. This last example brings me to my next tip.

 

Tip 3: Make Sure ALL Study Procedures Fit the Expedited Categories

The second critical step in determining if the research can be expedited is making sure ALL components of the research fit into one or more of the expedited categories. It is a common misconception when submitting for expedited review that the research has to “mostly” fit under one category, and that one category is what the research can be expedited under. In actuality, the study can only involve procedures on the expeditable list[5], therefore, if one study procedure doesn’t quite fit into a category, the study is not eligible for expedited review. It is recommended when filling out Quorum’s Expedited Review Request for Initial Review of Research form (F-179) you make sure to check all categories that apply to your research.

 

The categories of research eligible for expedited review include[6]:

Category 1: CPills-Blue-Circlelinical studies of drugs and medical devices only when condition (a) or (b) is met.

  1. (a) Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.)
  2. Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

 

Category 2: Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

  1. (a) from healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, 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; or
  2. from other adults and children, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week.

 

Petree-Dish-Blue-CircleCategory 3: Prospective collection of biological specimens for research purposes by noninvasive means.

Examples: (a) hair and nail clippings in a nondisfiguring 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) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) 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; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization.


Stethescope-Blue-CircleCategory 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. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.)

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) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

 

Petree-Dish-Blue-CircleCategory 5: Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects.  45 CFR 46.101(b)(4) This listing refers only to research that is not exempt.)

 

 

movie-camera-Magnifying-Glass-Blue-Circle

 

Category 6: Collection of data from voice, video, digital, or image recordings made for research purposes.

 

 

Three-People-Blue-Circle

Category 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. (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)

 

Tip 4: Read the Fine Print on the Expedited Categories

Some of the expedited categories are downright tricky, and need to be read VERY carefully to assess if they fit the research.  Here are some examples of types of research that may appear at first glance to qualify for expedited review, but ultimately, do not[7]:

  • Category 1:       This category involves clinical studies of drugs and devices when INDs and IDEs are not required. If a clinical investigation is a nonsignificant risk device (NSR) investigation it is possible that it could be eligible for expedited review if it is also determined to be minimal risk, but it is not guaranteed as the NSR definition[8] and minimal risk definition are not equivalent. Some studies determined to be NSR by the IRB could also be determined to pose greater than minimal risk and therefore, would not be eligible for expedited review.
  • Category 2:       This category involves collection of blood samples. In addition to ensuring the amount of blood collected does not exceed the stated limits within the 8 week period, it is important to remember that collections may not occur more than 2 times per week. Therefore, if a minimal risk study involves collection within the state limits requires 3 blood draws within a 1 week period, it may not be expedited. The 3rd blood draw would exceed to the limit of 2 collections per week.
  • Category 3:       This involves the collection of samples through noninvasive means. Some nasal swabbing techniques may seem to be minimal risk, but actually may not be eligible for expedited review if the swab goes past the nares. OHRP has provided clarification on this category and specified that the following are considered expeditable sampling techniques:
    • Vaginal swabs that do not go beyond the cervical os;
    • Rectal swabs that do not go beyond the rectum; and
    • Nasal swabs that do not go beyond the nares.[9]
  • Category 4:       This category is for collection of data through noninvasive procedures. MRIs are often utilized under this category. It is important to remember MRIs with contrast or sedation are not eligible for expedited review because the risks associated with the contrast or sedation products are considered greater than minimal risk.
  • Category 5: This category is for research involving material collected for nonresearch purposes, such as medical records or leftover specimens. A common area of confusion involves collection of specimens for standard of care. For example, a study may involve a biopsy occurring for standard of care.       If any additional specimen is taken in association with the standard of care biopsy for research purposes, it would not be considered eligible for expedited review because it does not meet the ‘nonresearch’ restriction. Another common mistake associated with this category is forgetting it applies if the study requires review of medical records but a medical record review is not the focus of the research – for example, reviewing records to confirm that an individual is eligible for the research.
  • Category 6: This category involves collection of data from voice, video, digital, or image recordings made for research purposes. The most common error associated with this category is forgetting it applies to the research. Often studies require a photograph or other recording, and this category is forgotten if it is not the focus of the research.
  • Category 7: This category primarily involves surveys and interviews. Like category 6, the most common error associated with this category is forgetting it applies when the survey or interview constitutes a very small portion of the research.

Tip 5: What to do if Your Research Requires Review at the Convened Board

Despite your best efforts and belief that your study qualifies for expedited review, you may find out that the study has been sent to the convened board for review. This happens. Don’t panic. It doesn’t always mean that there is an inherent problem with the research. The expedited reviewer may have concerns that the study does not clearly fit the minimal risk definition, all study procedures may not clearly fit into the expedited categories, the expedited reviewer may not believe one or more of the approval criteria are met, or the expedited reviewer may identify a concern that warrants review by more than their set of eyes alone. There is no appeal process to request the study resume expedited review after it has been sent to the convened board. Expedited reviewers have to feel comfortable and confident approving the study through the expedited process, as they are the only reviewer of the research, and expedited reviewers do NOT have the ability to disapprove a study under the regulations.[10] The expedited reviewer will provide a rationale for sending a study to the convened board so you will have a sense of why the decision was made.
In most cases, when a study is sent to the convened board it will not add significant delays to the review at Quorum. Most studies experience two or fewer days added to the standard turn-around times for expedited review. Quorum staff will be in contact with you about the revised timelines and to request additional information is needed to assist moving forward with the review.

Tip 6: Don’t Forget the Obvious Stuff

When trying to remember all of the above intricacies involved with expedited review, it can be easy to forget the obvious things that will help you move quickly and successfully through the process. So here’s your reminder to:

  • Remember to submit COMPLETE forms.
  • Remember to submit ALL forms needed. For example, if you need a waiver of consent, make sure to submit the Waiver or Alteration of Informed Consent Submission Form (F-043).
  • Respond quickly to IRB inquiries. Review may not be able to proceed until critical information is provided.
  • Submit high quality and clear protocols , consent forms, and other study related documents. Just because a study is minimal risk and possibly eligible for expedited review doesn’t mean that the quality of the study documents can be lower.
  • Contact Quorum if you have questions. If you’re not sure about any aspect of the expedited review process or requirements, ask Quorum. Our team will be happy to discuss your study in advance of submission to assist you.

Conclusion

Expedited review is a great way to save time, money and effort on the IRB review process. The trick is to make sure expedited review is requested when it’s appropriate for the research. For more information on Quorum Review’s Expeditable Review Services, our pricing, or whether your research qualifies, please email us at: BusDev@quorumreview.com.

References

[1] 45 CFR 46.110 and 21 CFR 56.110.

[2] This article discusses expedited review of new studies. It does not discuss expedited review for “minor changes in previously approved research during the period (of one year or less) for which approval is authorized” as authorized under 45 CFR 46.110(b)(2).

[3] Office for Human Research Protections (OHRP) – Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure. Available at: http://www.hhs.gov/ohrp/policy/expedited98.html. Accessed on November 19, 2014.

[4] Office for Human Research Protections (OHRP) – Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure. Available at: http://www.hhs.gov/ohrp/policy/expedited98.html. Accessed on November 19, 2014.

[5] Office for Human Research Protections (OHRP) – Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure. Available at: http://www.hhs.gov/ohrp/policy/expedited98.html. Accessed on November 19, 2014.

[6] Office for Human Research Protections (OHRP) – Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure. Available at: http://www.hhs.gov/ohrp/policy/expedited98.html. Accessed on November 19, 2014.

 

[7] Reference category definitions above for the full text.

[8] A significant risk device study is defined by 21 CFR 812.3(m) as a study of a device that presents a potential for serious risk to the health, safety, or welfare of a subject and (1) is intended as an implant; or (2) is used in supporting or sustaining human life; or (3) is of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise prevents impairment of human health; or (4) otherwise presents a potential for serious risk to the health, safety, or welfare of a subject. An NSR device investigation is one that does not meet the definition for a significant risk study.

[9] OHRP – Clarification of “noninvasive” in expedited review category 3. Available at: http://www.hhs.gov/ohrp/policy/Correspondence/index.html#noninvasive, Accessed November 20, 2014.

[10] 45 CFR 46.110 and 21 CFR 56.110.

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