QUALITY ASSURANCE IN CLINICAL TRIALS

QUALITY ASSURANCE IN CLINICAL TRIALS

a. Overview of quality assurance review

In many cases, new standards of care are based on the best treatment arm from clinical trials. The role of quality assurance is to ensure that all patients in each trial arm are treated comparably so the outcomes of these trials are valid. For each protocol  there are specific requirements for the patient treatment and for data that need to be submitted. For protocols with radiation therapy, these requirements (may) include (1) eligibility criteria to be on the protocol, (2) studies to be performed for the diagnosis and staging of disease, (3) specifica- tions for the definition of target volumes and critical normal tissues, (4) dose, and hence treatment planning specifications of radiation therapy, and (5) studies and timing for following the progress of the patient. Since protocols vary, the physicist needs to read the specific protocol for each patient in order to comply with the treatment and with the data submission requirements. The CRA and the physicist compile the data for review by the QA center. Please see appendix D for details on each of the resource and review centers.

The timing and extent of QA review depends on the cooperative group and the protocol. In general, there are different levels of detail of the QA review. For some protocols, the radiation therapy is standard and not likely to influence the analysis of the study question. For example, many acute lymphocytic leukemia protocols test different chemotherapy regimes and include whole brain irradia-tion for some patients. The parallel-opposed fields irradiation is straightfor-ward. Quality assurance review will include only a chart review to assure that the irradiation was performed and that the fraction dose and total dose were as prescribed by the protocol.17 Another level of QA review may occur for protocols that, as in the simple review, include standard radiation therapy without a radiation question but with concern for efficacy and toxicity caused by the radiation. An example is a pro-tocol for lung cancer that is examining the efficacy of one drug versus another with all patients receiving the same radiation therapy. The QA review will occur after the patient has completed treatment and will include a thorough review of the target volumes (using diagnostic imaging studies, surgery reports, etc.), a review of the treatment plan, a review of the dosimetry including dose to specified critical organs (such as the spinal cord), a review of the treatment delivery from portal films or portal images, and a chart review to verify the dose was delivered as specified.

A comprehensive level of quality assurance is usually applied for protocols that ask a radiation question and/or include advanced technology radiation therapy. For example, a COG medulloblastoma protocol that tests 18 Gy versus 23.4 Gy to the posterior fossa and mandates 3D conformal treatment would have comprehensive QA at QARC. For this the treatment plan and treatment fields will be required to be reviewed before, or at least within a few days of beginning treatment. The diagnostic imaging acquired for staging will be reviewed concurrent with  the planning CT scan. The accuracy of the delineation of the posterior fossa as the target volume will be reviewed, as will the treatment plan.

The prescribed fractional and total dose will be verified. Simulator films will be compared to DRRs. If there are any questions from this initial review, interactions will occur between the QA center and the treating institution. The process will be iterated until there is agreement among the physician, the radiation therapy principal investigator  (PI) for the protocol, and the QA center’s physician that the treatment is in compliance with the protocol and that treatment shall be delivered. At the completion of treatment, a final review will be performed. The chart will be checked to verify that the treatment was delivered as planned, portal images will be verified, and the treatment plan again verified