Risk of Common Procedures

There is agreement about the nature of risk from some procedures. While the CHOP IRB endeavors to maintain consistency across its committees and expedited reviewers, the proposed subject population, the setting and the persons conducting the research vary and therefore, the IRB may come to different conclusions about the risk of the same procedure for different studies.

A complete listing of the minimal risk procedures listed by OHRP and FDA along with explanations for each category is provided on the Expedited Review page of the IRB's website.

Medical Procedures (without Ionizing Radiation)

Blood Draw / Venipuncture

Expedited Review:
Minimal risk research is be eligible for expedited review but the criteria depend on the funding source.

Federally Funded Research and Research Subject to FDA Regulations

Expedited Review:
For child participants to be eligible, the volume of blood must be limited to either 3 mL/kg or 50ml, whichever is less, over 8 weeks and no more frequently than 2x per week. The volume for adults is limited to 500 mL, over 8 weeks and no more frequently than 2x per week.

Full Board Review:
The full board must review all federally funded protocols that involve volumes of blood greater than or more frequent than what is list above.

Non-Federally Funded Research

The IRB follows the NIH Clinical Center Guidelines for the maximum volumes that it will approve for research only purposes. The IRB may choose the reduce the amount and frequency depending on the age of the subject, their underlying disease or condition and the anticipated blood losses from other causes (e.g. surgery, routine care, etc.)

Adults:
"The amount of blood that may be drawn from adult patients and volunteers (i.e., those persons 18 years of age or older) for research purposes shall not exceed 10.5 mL/kg or 550 mL, whichever is smaller, over any eight week period."

Children:
"For pediatric patients, no more than 5 mL/kg may be drawn for research purposes in a single day, and no more than 9.5 mL/kg may be drawn over any eight-week period."

IV catheter insertion Generally the IRB considers IV insertion to be minimal risk whether for infusion or for use for multiple blood draws (eg, a PK study). However, the discussion should address the number of insertion attempts that will be permitted, the skill of the individuals placing the catheter and efforts to mitigate subject discomfort (e.g., use of topical anesthesia).
Skin Biopsy

For federally funded research and research subject to FDA regulations, skin biopsy is not on the list of procedures which may be reviewed using expedited procedures. Therefore, all federally funded or FDA-regulated protocols involving skin biopsy must go to the full board. Protocols involving skin biopsy that are not federally funded or subject to FDA regulations may be reviewed using expedited procedures.

Minimal Risk (requires full board review if federally funded or subject to FDA regulations):
Skin biopsies that are limited to a few millimeters and do not require sutures are considered by the CHOP IRB to be equivalent in risk to i.v. catheter insertion.

Greater than Minimal Risk:
Any skin biopsy that requires suturing will be considered a minor increase above minimal risk. In addition, the subject's underlying condition might make the procedure greater than minimal risk (e.g. coagulopathy, hemophilia).

Additional Biopsies

Endoscopic biopsy of the GI tract, liver biopsy and kidney biopsy may be performed as part of clinical care or as part of a monitoring procedure needed to assess treatment outcome. In these situations, the risks of the procedures are clinical or are considered necessary as part of the benefit of the research treatment. However, when additional biopsies are obtained for research-only purposes and the research is federally funded or subject to FDA regulations, the full board of the IRB must review the risks.

Minimal Risk (requires full board review if federally funded or subject to FDA regulations):
The IRB has reviewed the risks associated with additional lower and upper GI biopsies and generally finds them to be no greater than minimal risk when they are part of a clinically indicated procedure. When the study is federally funded or FDA-regulated, full board review is required; otherwise, the research may be reviewed using expedited procedures.

Greater than Minimal Risk:
Liver and kidney biopsy have risks of bleeding that exceed what is considered minimal risk. These may be either a minor increase above minimal risk or, depending on the the subjects underlying medical condition, greater than a minor increase.

General Anesthesia and Sedation

The IRB considers sedation and general anesthesia to be a minor increase above minimal risk for healthy children and when the procedures are performed by a qualified practitioner. For children that are sicker (American Society of Anesthesiologists Physical Status 3, 4 or 5), the IRB will review the investigational plan to determine whether or not the procedures qualify as a minor increase.

Prolongation of the duration of sedation and general anesthesia may be considered either minimal risk or a minor increase above minimal risk, depending on the duration and clinical circumstances.

Repeated requirements for sedation and general anesthesia may be either a minor increase above minimal risk or greater than a minor increase depending on the number of procedures and the child's underlying condition.

Gadolinium or Other Contrast Agents The IRB has generally determined that iv contrast agents are a minor increase above minimal risk. For research approved under 45 CFR 45.405 (direct benefit), the IRB may permit one parent's signature is all that is needed provided the radiologic procedure requiring contrast is essential for monitoring the study outcome (i.e., contrast is required as part of the assessment of the intervention providing direct benefit). However, for all other research, the IRB will approve the research under 45 CFR 46.406 and require two parents signatures.

Radiology Procedures Involving Ionizing Radiation

The CHOP IRB in collaboration with the UPenn Radiation Safety Committee and with input from CHOP Radiology as established the following general guidelines for level of risk from radiation exposure for research procedures.

Minimal Risk Exposures to ionizing radiation of up to 100 mrem/year (1 mSv) is generally considered minimal risk. The UPenn RDRC may determine that there additional factors that increase the risk for a particular subject population.
Minor Increase Above Minimal Risk Exposures to ionizing radiation of 101 - somewhere between 500-5000 mrem/year are consistent with a minor increase above minimal risk. The determination on the upper limit of permissible exposure will be determined by the UPenn RDRC and will depend on subject factors and the indication.
Greater than a Minor Increase Above Minimal Risk Exposures to ionizing radiation >5000 mrem/year will be considered greater than a minor increase above minimal risk. This level of radiation exposure will only be approved for research where the radiation exposure is related to an intervention providing a direct benefit to the research subjects.

Top