ISSUES:

1. Radiation is given as medically indicated, but really it is not.

2. Radiation procedures are not disclosed in the protocol and therefore not reviewed by the IRB.

3. Who is responsible for the decision?   The PI, IRB, RSC?

RSC POSITION STATEMENT (adopted on 12/13/2001):

The determination of the "medical necessity" of a procedure is often very enigmatic and often context, i.e., disease-specific.   A given procedure (chest x-ray for example) in one context is medically necessary and in another context it is a research-related exposure.   The RSC has neither the resources nor the clinical background for all the diseases studied at NIH to make this determination, no matter how thorough we attempt to be.   The RSC should NOT attempt to determine whether or not a procedure is medically indicated, and instead relegate this determination to the IRB system and Clinical Directors.

RSC REQUEST:

• Raise the awareness of this issue with the IRBs and impress upon them that it is crucial that principal investigators (PIs) disclose all radiation procedures administered in a protocol (as required on the NIH form 1195, attached).

• Remind IRBs that, in accordance with the NIH OHSR 's IRB protocol review standards (attached), IRBs are responsible for discussing, designating and documenting the indication of the radiation usage in protocols.

• Note that the RSC has recently begun stipulating that PIs "provide documentation that the IRB concurs with the assessment that all other radiation studies, not listed in the NIH form 88-23(a), are in fact clinically indicated".    Acceptable documentation is a copy of the relevant IRB meeting minutes or a confirmatory memo or email from the IRB Chair.

• IRBs are encouraged to draft guidelines for discerning clinical vs. research indicated radiation usage (example: NCI draft guidelines were distributed with the HSRAC agenda).

ADDITIONAL INFORMATION:

• CC Policy and Communications Bulletin, Medical Administrative Series, M93-1, "Research Involving Human Subjects at the Clinical Center: Structure and Process"

Definitions, pg 3:   "At the Clinical Center, biomedical research is any process that seeks to secure new information from humans or about humans that differs from customary medical (or other professional) practice."

• Protomechanics , Chapter VI, excerpt:

Medically indicated... for diagnosis or treatment when such use is considered to be standard patient care.

NOTE :   Important to recognize that a procedure with radiation exposure that is readily accepted as standard patient care, when done more than once , may become classified as "for research purposes."

If the radiopharmaceutical or x-ray procedures in a protocol are of the appropriate type and number used in the practical management of the condition, the radiation exposure is considered medically indicated and does not require RSC review.

If uses of radiation or radioactive materials do not meet the criteria for "medically indicated," they are regarded as "indicated for research."

EXAMPLES:

• ROSIE-CT study...patients with hemiplegia.   The first CT scan is performed as "standard of care", to rule out hemorrhagic damage to the brain prior to some form of anticoagulation therapy (radiation use is deemed medically indicated).   A series of four more CT scans are performed to evaluate for shrinkage of the brain or hemorrhage.   Since these additional scans are not normally performed as the standard of care for stroke, absent any other indications, they are deemed research oriented.

• PET study performed in patients with acute lymphproliferative syndrome (ALPS).   The first scan is administered for research purposes.   If a node begins growing rapidly, a second PET scan, to exclude lymphoma, is performed (deemed medically indicated).  

• CT guided ablation (cauterization) of painful tumor metastases.   CT RFA (radiofrequency ablation) shows promise, but has not yet been proven to be effective - no "evidence base".   Hence, radiation use deemed research indicated.