Frequently Asked Questions

When do I need to submit a protocol to CACTIS?
When do I need to submit a protocol to CAMRIS?
When do I need to submit a protocol to the Nuclear Medicine Research Committee?
When do I need to submit a protocol to RDRC?
Do I need a radiology sub-investigator on the protocol?
Do radiology sub-investigators require support on the grant?
Publication/authorship issues with radiology sub-investigators.
Do experimental imaging studies require UPHS clinical radiology reports?
What if the imaging studies are being reviewed by outside imaging experts?
Who is responsible for issuing a clinical report for SOC and non-SOC imaging studies?
What is required for consent forms for investigational MRI studies?
What is required for consent forms for investigational CT studies?
What is required for consent forms for investigational NM/PET studies?
What should an ICF say about the risks and benefits of experimental imaging?
When do I need an “incidental finding” clause in my consent form?
Can experimental imaging be performed in the clinical radiology center?
How can examinations that are not standard of care be billed to a grant?
Are there scheduling constraints for experimental imaging?
Are research coordinators required to be present during performance of experimental imaging?
The sponsor requires that all imaging be performed on the same equipment.
The sponsor requires specific imaging protocols for the study.
The sponsor requires completion of technical imaging forms during the study.
The sponsor requires anonymized image submission to a central site.

When do I need to submit a protocol to CACTIS?

A protocol for which any of the following definitions apply to the CT imaging must be submitted to CACTIS and RDRC for review.

The protocol requires the use of novel imaging sequences (e.g. perfusional CT) that are not approved for routine SOC imaging.
The protocol requires the use of standard clinical CT imaging in addition to that which would be defined as the clinical SOC. This includes imaging studies performed at times not used for SOC, imaging studies of anatomic regions that are would not routinely be obtained during normal SOC, or the use of contrast agents or doses that would not be used during normal SOC.
The protocol requires the use of imaging parameters or sequences that are not part of the clinical standard imaging protocols and results in a radiation dose in excess to that which would be received by the subject during clinical standard of care CT imaging.

In addition, if either of the following holds true it is strongly recommended that the protocol be reviewed by the CIC:

The protocol requires the use of imaging parameters or sequences that are not part of the clinical standard imaging protocols of the radiology department, but do not impart an radiation dose greater than that which the patient would normally receive during routine SOC CT imaging.
The clinical protocol includes an imaging manual that specifies certain imaging constraints in order to provide uniformity of imaging within the protocol.

Note that clinical scans cannot be routinely altered to fit sponsor-requirements. The CIC will initiate consultation with the appropriate CT divisional chief to ensure that the alternate imaging sequences required by the protocol can be put into place routinely for study patients imaged in the clinical CT center.

The CIC core of the ACC provides free initial protocol consultations, during which a CT expert will review the protocol to determine if any of the above situations apply. The CIC consultation would then provide recommendations for further administrative oversight and regulatory guidance to the CC PI, including an estimation of fees for CIC services.

When do I need to submit a protocol to CAMRIS?

A protocol for which any of the following definitions apply to the MRI imaging must be submitted to CAMRIS for review.

The protocol requires the use of novel imaging sequences and/or novel imaging hardware (coils) that are not FDA approved.
The protocol requires the use of standard clinical MRI imaging in addition to that which would be defined as the clinical SOC. This includes indicated imaging studies performed at times not used for SOC, imaging studies of anatomic regions that are would not routinely be obtained during normal SOC, or the use of contrast agents or doses that would not be used during normal SOC.

In addition, if either of the following holds true it is strongly recommended that the protocol be reviewed by the CIC:

The protocol requires the use of FDA approved sequences that are not part of the clinical standard imaging protocols of the radiology department.
The clinical protocol includes an imaging manual that specifies certain imaging constraints in order to provide uniformity of imaging within the protocol.

Note that clinical scans cannot be routinely altered to fit sponsor-requirements. The CIC will initiate consultation with the appropriate MRI divisional chief to ensure that the alternate imaging sequences required by the protocol can be put into place routinely for study patients imaged in the clinical MRI center.

The CIC core of the ACC provides free initial protocol consultations, during which an MRI expert will review the protocol to determine if any of the above situations apply. The CIC consultation would then provide recommendations for further administrative oversight and regulatory guidance to the CC PI, including an estimation of fees for CIC services.

When do I need to submit a protocol to the Nuclear Medicine Research Committee?

A protocol for which any of the following definitions apply to the nuclear medicine (including PET and SPECT) imaging must be submitted to the PET Imaging Committee for review.

The protocol requires the use of a novel imaging technique (e.g. dynamic PET, delayed time point PET) that are not used in routine SOC imaging.
The protocol requires the use of standard clinical nuclear medicine imaging in addition to that which would be defined as the clinical SOC. This includes imaging studies performed at times not used for SOC, imaging studies of anatomic regions that are would not routinely be obtained during normal SOC.
The protocol requires the use of PET imaging using tracers other than FDG.

Note that clinical acquisition protocols, including patient handling and timing of imaging cannot be routinely altered to fit sponsor requirements. The CIC will initiate consultation with the Nuclear Medicine Divisional to identify how protocol requirements can be met.

The CIC core of the ACC provides free initial protocol consultations, during which a Nuclear Medicine expert will review the protocol to determine if any of the above situations apply. The CIC consultation would then provide recommendations for further administrative oversight and regulatory guidance to the CC PI, including an estimation of fees for CIC services.

When do I need to submit a protocol to RDRC?

Any time a research subject will receive a radiation dose (diagnostic or therapeutic) in excess of that which they would receive in the course of normal medical care, the protocol must be reviewed by the radiation safety committee. This includes all protocols submitted to CACTIS or the PET Research Committee that utilizes experimental (non-SOC) CT and/or nuclear medicine imaging.

Do I need a radiology sub-investigator on the protocol?

Radiology co-investigators are not required for protocols in which SOC imaging only is utilized. For protocols where alternate image acquisition parameters or techniques is mandated, it is advised that a radiology co-investigator be identified. For protocols where non-SOC imaging is used, a radiology co-investigator may be used to perform clinically required imaging reports. When one or more experimental imaging techniques are involved, or when image guided biopsy is performed for research purposes, a radiology co-investigator is mandatory.

Do radiology sub-investigators require support on the grant?

Radiology co-investigators may or may not require salary support for grant participation. At times, radiologists may agree to perform service work in support of a clinical trial without the requirement for salary or other support. Often, a radiologist will agree to provide service in exchange for scholarly recognition on publications resulting form the results of the clinical trial. At other times, direct salary support for the radiologist and/or support staff maybe required, especially when significant effort is expended in the oversight of imaging procedures, form completion, or clinical reporting. Investigators may access radiologist support independently, or may use the CIC protocol support services to access to radiologist service for clinical trial support.

Publication/authorship issues with radiology sub-investigators.

When protocol support is provided by the CIC, it is expected that when appropriate, co-authorship will be offered to radiology and at times support personnel when significant effort in support of the clinical trial is provided. It is recognized that such authorship agreements in multi-site industry and co-operative group trials may not be feasible. However, it is expected that whenever investigators initiate secondary publications based on results from such studies that included radiology support for data acquisition, all attempts will be made to include the study radiologists as co-authors. For investigator initiated studies, it is expected that the study radiologist(s) will be included as co-authors for all publications that include the use of data derived imaging and/or image analysis.

When radiologist services are obtained directly by the investigator, authorship agreements are to be discussed by the parties involved.

Do experimental imaging studies require UPHS clinical radiology reports?

In rare instances, an imaging report may not be required when imaging is performed in the course of a clinical trial. These cases arise when the formal radiologic interpretation is not expected to yield useful medical information, and when the risk of unnecessary medical, radiologic, or surgical follow-up based on incidental imaging findings is expected to outweigh any potential medical benefit of radiologic interpretation. Such examples include normal subjects who undergo imaging to obtain normative anatomic or physiologic data, or limited imaging studies (e.g. single slice CT for abdominal fat quantification), where the medical value of radiologist review is expected to be extremely limited.

Final decisions on the requirements for radiology review are made by the appropriate experimental imaging review committee.

What if the imaging studies are being reviewed by outside imaging experts?

The presence of an outside imaging review by image experts does not obviate the requirement for UPHS radiologic review for imaging performed in the course of a clinical trial. Centralized reviews are often performed much later that the time of image acquisition, potentially nullifying the medical benefit of radiologist findings. Furthermore, it is not possible to ensure and document the receipt by clinical care givers of clinically relevant information from centralized image review. As such, except when exceptions are noted by the experimental imaging review committees, all imaging performed within UPHS in the course of clinical imaging must be formally reviewed by a UPHS radiologist or other imaging expert, with appropriate clinical documentation in the medical and research record of the results of such review.

Who is responsible for issuing a clinical report for SOC and non-SOC imaging studies?

When imaging studies are paid for by third party payers, clinical reports are provided by the on-service radiologist within twenty-four hours of study performance. Similarly the appropriate on-service radiologist will issue clinical reports when family account billing including professional fees are utilized, or when “reader services” within the appropriate research modality are utilized

When professional fees are waived for family accounts, or when research services are utilized without the “reader service” fee, then it is the responsibility of the PI to ensure that one or more co-investigator radiologists will interpret the study and issue a clinical report in a timely fashion.

What should an ICF say about the risks and benefits of experimental imaging?

In general, it is not permissible to indicate that participation in a study, including participating in research-directed imaging examination, will accrue any benefit to the study participant. In addition, undergoing research-directed imaging studies accrues certain risks. Modality specific risks, with appropriate ICF language, are identified in the appropriate research modality web pages.

When do I need an “incidental finding” clause in my consent form?

Whenever imaging that would not normally be performed for clinical care occurs, and the images are reviewed by a radiologist, the potential for the discovery of an “incidental finding” exists. The possibility and the nature of such incidental findings will depend on the type of imaging performed, and the relationship of such imaging to any similar imaging which occured prior to, or will occur after study participation. The possibility of an incidental lesion is highest when a new imaging modality (one not normally utilized for a given subject) is used, or when anatomic areas not normally imaged are imaged for the purposes of research.

As discovery of incidental lesions can lead to additional laboratory testing, and/or biopsy or surgery, the risks of incidental lesion detection should be discussed in the ICF.

Can experimental imaging be performed in the clinical radiology center?

In general, experimental imaging studies cannot be performed in the clinical imaging centers. Even when the clinical units are capable of acquiring the experimental images, the professional staff which runs the clinical imaging centers will not have the training or knowledge of the experimental techniques to be used. As such, research imaging services are generally required.

When research-directed protocols are used for clinical care and deviate minimally from the clinical imaging protocols used for the same clinical indications, specialized image acquisition protocols to meet the demands of the clinical study may be able to be performed in the clinical imaging center. These needs are reviewed on a case by case basis by the clinical imaging services. The CIC can provide protocol-specific review to discuss the feasibility of performing study-directed imaging in the clinical center.

How can examinations that are not standard of care be billed to a grant?

There are two potential mechanisms for billing non-SOC imaging studies.

Research Billing Accounts
Research Service Centers

Note that for each of the above, separate profession (radiologist) and technical (machine, technologist time) fees must be considered.

Research Billing Accounts

Research billing accounts are accounts that the clinical department of radiology provides to investigators who are obtaining imaging that would otherwise adhere to clinical imaging protocols, but that for a given reason cannot be billed to third-party payers. This may include:

Imaging that would not normally be provided in the course of clinical care.
Imaging that is duplicative of prior imaging, or is performed more frequently than normally allowed by third-party payers.
Imaging that is required to be performed at the University of Pennsylvania in patients whose insurance capitates them to an alternate imaging center.

For research billing accounts, the radiology department sets technical and profession fees for the required services, and the grant is billed accordingly. The research billing account mechanism presumes that the imaging to be performed is based on the SOC imaging protocols used in the department. Deviations form these protocols based on sponsor requirements cannot normally be adhered to unless explicitly agreed to by the appropriate clinical divisional chief. In addition, the use of the same scanner in longitudinal studies cannot be guaranteed when imaging is performed under a Family Account mechanism.

It is expected that research billing account services will include both the technical and professional fees, which then results in the issuance of one or more clinical radiology reports at the time of imaging. At times, investigators may wish to use one or more dedicated clinical radiologists who are named as sub-investigators on the trial. In such cases, the professional fees can be waived, once confirmation from the appropriate radiologist(s) is/are obtained.

Research Service Centers

Research centers such as CACTIS, CAMRIS, and the Nuclear Medicine Research Center provide a fee structure for the use of imaging services. Use of these services generally require the use of one of the research scanners, but provide for a more controlled environment when variations from normal clinical routine imaging are required. The research center fees provide only for the technical component of the exam. Research committe approval requires that either a) a radiologist is named as co-investigator to the protocol and that radiologist assumes responsibility for both the technical aspects of the imaging acquisition and the issuance of clinical reports, or b) a “clinical service” fee is included, in which case the examination will be reported by the appropriate clinical service(s) in the course of the normal clinical day.

Are there scheduling constraints for experimental imaging?

The availability for performing experimental imaging studies will depend on the nature of the imaging equipment to be used, the availability of research technical staff, and at times the balance between clinical and research needs on shared imaging equipment. Clinical trial teams will be instructed on details of scheduling experimental imaging studies. Alternately, the CIC can manage the logistical details of experimental imaging, including scheduling of exams.

Are research coordinators required to be present during performance of experimental imaging?

As the research imaging services are staffed (and on occasion housed) separately than the clinical imaging services, ancillary patient support staff (i.e. patient aides, nursing, etc.) is not usually available for chaperoning patients during research-directed imaging appointments. While the technical research staff will monitor all patients while research imaging procedures are performed, these personnel cannot maintain responsibility for research subjects before imaging begins or after the study is complete. As such, clinical coordinators or other personnel are usually required to bring patients to scheduling research exams, and escort patients from the imaging center after the imaging procedure is complete.

Policies within individual research imaging centers will vary, but in general clinical research personnel need not always stay in the research imaging center during the performance of the examination. However, the clinical research coordinator, another representative of the clinical trial team, or a designated member of the radiology research personnel (radiologist or radiology research coordinator) must be available by telephone during all research imaging studies should urgent patient issues arise during the course of the imaging study.

The sponsor requires that all imaging be performed on the same equipment.

In general, this is difficult to guarantee if the imaging is performed as SOC, is reimbursed by third party payers as a clinically routine imaging study, and performed in the clinical imaging center.

When such research-directed imaging is to be performed in the clinical imaging center as SOC radiology service, the clinical imaging core will provide guidance to clinical investigators on which imaging equipment is best used for the imaging examination, and how imaging should be scheduled. However, it is recommended that clinical research personnel accompany patients to these examinations (or that the CIC services be used for this purpose) to provide guidance to the clinical imaging personnel on the needs of the trial. However, the radiology department cannot guarantee such procedural adherence for examinations performed in the clinical imaging center.

Alternately, after consultation with the study sponsor, if the research budget allows for direct coverage of all imaging in the study, studies may be performed in the research center and billed to the research grant. In such cases, the study may be in compliance with protocol mandates.

The sponsor requires specific imaging protocols for the study.

In such cases, the study imaging manual provided by the sponsor should be reviewed by the CIC to determine if SOC imaging procedures are in compliance with the protocol’s imaging guidelines. In cases where the imaging is clinical SOC and the imaging guidelines adhere to the clinical SOC acquisition protocols of the radiology department, no further administrative oversight is required.

When acquisition protocols differ from those of the SOC clinical imaging procedures, special administrative oversight is required. In general, compliance with protocol-specific imaging guidelines is best performed in the research imaging center. When protocol budget does not allow for billing of imaging studies to the research grant, the CIC will advise the study PI on the possibility for study compliance within the clinical imaging center. In such cases, attendance at all imaging exams by clinical research personnel is recommended to guide the clinical imaging personnel on the specific imaging requirements of the study.

The sponsor requires completion of technical imaging forms during the study.

The CIC will review such forms to determine whether they can easily be completed by the technical staff at the time of imaging. In such cases, the PI may elect to use the CIC services to provide oversight for form completion. Alternately, clinical imaging personnel may assume responsibility for providing the clinical research personnel with the appropriate forms at the time of imaging. Retrospective form completion in such cases is usually not possible by the clinical imaging personnel.

The sponsor requires anonymized image submission to a central site.

The department of radiology provides a per case rate for the provision anonymized disks to the clinical research personnel. Turn-around time depends on the number of studies submitted. In such cases, it is the responsibility of the clinical research personnel to forward the image sets to the central imaging site For studies in which image analysis is undertaken by the CIC tumor response (RECIST) service, anonymized disks can be provided at a reduced fee to the clinical research team.

Penn Center For Biomedical Imaging

Translating Clinical Radiology Research from Bench to Bedside