New and Improved: The NCI’s Best Case Series Program now designated as a protocol

From left to right, Cancer Research Training Award
fellow Jeans Santana, Dr. Farah Zia, and
Dr. Oluwadamilola Olaku discuss the
NCI Best Case Series.

A patient with cancer who has exhausted commonly prescribed options may have a treatment suggested to them by their doctor that is not traditionally indicated for cancer. The patient agrees to the therapy, takes it, and finds themselves significantly better, or even cured. Although the doctor thinks he may have a promising treatment on his hands, he most likely does not have the resources available to conduct a large clinical trial or engage in laboratory research. What can he do next? He can submit case reports of these patients to the NCI Best Case Series (BCS) Program, which has recently been approved as a protocol. This long-standing program was initially developed in 1991 in response to an evaluation by the Office of Technology Assessment (OTA), per request by the United States Congress. From 1991-1997, it was overseen by the NCI’s Cancer Therapy Evaluation Program of the Division of Cancer Treatment, Diagnosis, and Centers (DCTC). The objective was to assess cases that used alternative regimens to treat cancer and determine if there was enough evidence for NCI to support more research of the treatment, such as the initiation of a clinical trial. With the establishment of NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM) in 1998, management of the program was transferred. Currently, it is under the direction of the Case Review and Intramural Science Program (CRISP) of the OCCAM. The Director of CRISP is Dr. Farah Zia and the CRISP Coordinator is Dr. Oluwadamilola Olaku. Dr. Zia is the Principal Investigator of the NCI BCS Program.

After a recent review by the Office for Human Research Protections, the NCI BCS Program was determined to meet criteria for clinical research. This led to the development of a written protocol which subsequently was reviewed and approved by NCI’s Special Studies Institutional Review Board. The protocol describes in detail the processes and procedures involved in the selection and evaluation of cases for review. The change to a protocol may make publishing case reviews easier because Dr. Zia notes, “Journal reviewers will know that the protocol used to review the cases achieved ethics clearance.”

Although there is no change to submission criteria, under the protocol there are now “eligibility” criteria. According to Dr. Zia, “As with all protocols, these criteria are established to ensure that the results of the research are reliable.”

Under the new protocol, the investigators will provide the CAM practitioner with a “mini-consent” form to document that a patient, whose medical case history is being considered for submission, agrees to the release of their basic contact information (e.g., name, telephone number) to OCCAM. Once OCCAM receives this “mini-consent” one of the BCS investigators will contact the patient asking for their written consent to have their identified medical records reviewed as part of the study. This step is an important requirement for the new protocol — it ensures that all of the patients receive accurate and consistent information regarding the Program (as opposed to just receiving information from their doctor) and it makes clear that their medical records will be viewed by different people associated with the program (including the BCS investigators, pathologists, radiologists, and external reviewers).

Despite the fact that patients involved in this research have already completed treatment, their participation is extremely valuable. Dr. Zia comments that when patients provide consent to participate in the study, “they are helping to contribute to the evidence for a specific cancer CAM treatment. If this leads to the development of a new, approved therapy, future patients would benefit.”

Analysis of case reports takes place in two parts: a pre-research assessment and a comprehensive review. Practitioners initially submit a de-identified summary of each case planned for submission, which is reviewed for eligibility to the Program. The summaries describe the treatment and are used to determine that the patients had a diagnosis of cancer by tissue biopsy, that there is detectable disease on radiographic imaging prior to the start of the unconventional regimen, and that conventional therapies were not used alongside or within 4 weeks of the unconventional therapy. Once cases that meet eligibility criteria are identified, BCS investigators obtain patient consent and request their complete medical records from the submitting practitioners. Under the new protocol requirements, practitioners may send a minimum of 3 and up to 20 case reports to be reviewed. However, if CAM practitioners only have one or two cases available, they are encouraged to contact CRISP. While one or two cases are not enough to be eligible for a full review, the CRISP staff may be able to provide some feedback to the practitioners.

CRISP staff review radiographs submitted
to the NCI Best Case Series.

During the comprehensive review, the medical records, pathology slides, and radiographs are carefully examined by BCS investigators, along with pathologists and radiologists from the NIH Clinical Center (the NCI Laboratory of Surgical Pathology and the NIH Diagnostic Radiology Department). Following this review, the cases are rated as “Persuasive,” “Supportive,” or “Unevaluable.” Cases receiving a “Persuasive” or “Supportive” rating are sent to external experts (including oncologists, basic scientists, and clinicians) for further discussion and recommendations on whether NCI-initiated research is warranted for the specific intervention. BCS investigators will use the experts’ opinions to evaluate the utility and estimate the cost of conducting a research study examining the alternative treatment. A recommendation is presented to the Director of the Division of Cancer Treatment and Diagnosis, who makes the final decision regarding subsequent research of the alternative cancer therapy. Practitioners may try to bring attention to their interesting cases on their own; however, the obvious benefit of submitting to the protocol is that it provides another level of oversight to the case histories — it helps validate the information. As a result, Dr. Zia says, “You have the strength of The NCI Best Case Series Protocol validation standing by you.”

Due to the nature of the NCI BCS program — that doctors have used unconventional treatments, not specifically indicated for cancer — some physicians may be wary about submitting their cases for review. And this wariness may explain why many submitted cases are from outside of the U.S. where alternative medical treatments are more accepted. Dr. Zia notes that the BCS investigators make it clear to submitting doctors that the BCS Program is not out to report them. Rather, states Dr. Zia, “We are researchers interested in seeing those cases and in moving forward” with the science.

“The NCI BCS program continues to provide cancer CAM practitioners a very distinctive opportunity to have their treatment modalities reviewed objectively,” Dr. Zia notes. “Of course, a decision for NCI to pursue follow-up research is the ultimate desire of all submitters; however, other positive outcomes may include having OCCAM publish the case series review in a peer-reviewed journal. This would bring scientific attention to the therapy represented in the case series and may result in research collaborations.”

If you have any questions about the NCI BCS Program or are interested in submitting case reports for review, please visit http://cam.cancer.gov/indentifying_novel_cam_therapies/
best_case_series_program.htm or contact Dr. Oluwadamilola Olaku (301-435-7980; olakuo@mail.nih.gov) for more information.