R-IDEAL: A Framework for Systematic Clinical Evaluation of Technical Innovations in Radiation Oncology

Abstract

The pace of innovation in radiation oncology is high and the window of opportunity for evaluation narrow. Financial incentives, industry pressure, and patients’ demand for high-tech treatments have led to widespread implementation of innovations before, or even without, robust evidence of improved outcomes has been generated. The standard phase I–IV framework for drug evaluation is not the most efficient and desirable framework for assessment of technological innovations. In order to provide a standard assessment methodology for clinical evaluation of innovations in radiotherapy, we adapted the surgical IDEAL framework to fit the radiation oncology setting. Like surgery, clinical evaluation of innovations in radiation oncology is complicated by continuous technical development, team and operator dependence, and differences in quality control. Contrary to surgery, radiotherapy innovations may be used in various ways, e.g., at different tumor sites and with different aims, such as radiation volume reduction and dose escalation. Also, the effect of radiation treatment can be modeled, allowing better prediction of potential benefits and improved patient selection. Key distinctive features of R-IDEAL include the important role of predicate and modeling studies (Stage 0), randomization at an early stage in the development of the technology, and long-term follow-up for late toxicity. We implemented R-IDEAL for clinical evaluation of a recent innovation in radiation oncology, the MRI-guided linear accelerator (MR-Linac). MR-Linac combines a radiotherapy linear accelerator with a 1.5-T MRI, aiming for improved targeting, dose escalation, and margin reduction, and is expected to increase the use of hypofractionation, improve tumor control, leading to higher cure rates and less toxicity. An international consortium, with participants from seven large cancer institutes from Europe and North America, has adopted the R-IDEAL framework to work toward coordinated, evidence-based introduction of the MR-Linac. R-IDEAL holds the promise for timely, evidence-based introduction of radiotherapy innovations with proven superior effectiveness, while preventing unnecessary exposure of patients to potentially harmful interventions.

Single dose partial breast irradiation using an MRI linear accelerator in the supine and prone treatment position

“…This study was designed as a RT predicate study for evidence based-introduction of the MRI-linac according to the R-IDEAL framework for clinical evaluation of technical innovations in radiation oncology [23] . Twenty patients were selected from 2 earlier studies on MRI-guided preoperative single-dose partial breast irradiation.…”

“…According to the R-IDEAL design for RT-based innovations, a sample size of 20 patients should be adequate for this predicate study [23] . The primary study endpoint was defined as the percentage of feasible plans with respect to target coverage and OAR constraints.…”

Target coverage and dose criteria based evaluation of the first clinical 1.5T MR-linac SBRT treatments of lymph node oligometastases compared with conventional CBCT-linac treatment

“…A R-IDEAL [23] stage 0 study simulating the dosimetric impact of online replanning for SBRT of lymph node oligometastases on the 1.5T MR-linac compared to online position correction showed beneficial dosimetric outcomes and a reduction of unplanned violations of dose constraints [18]. The purpose of this study was to perform a target coverage and dose criteria based evaluation of the clinically delivered online adaptive radiotherapy treatment compared with simulated conventional CBCT-linac treatment.…”

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial

“…Our primary aim will be to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). By virtue of its assessment of clinical effectiveness and safety of the use of weekly MRI for dose adaptation, this study is a stage 2a/2b study as per the R-IDEAL framework for systematic technology assessment in radiotherapy [16] ( Annex 1 – Supplementary material ).

Supplementary data 1

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