International clinical trials setting for rare cancers: organisational and regulatory constraints—the EORTC perspective

Abstract

Rare diseases are a serious public health problem that presents unique challenges to many countries. There is no internationally accepted definition for rare diseases. Patients suffering from rare cancers often face challenges, including late or incorrect diagnoses, difficulties finding clinical expertise and accessing appropriate treatments, and uncertainty in clinical decision making, with difficult and rare access for these patients to clinical trials. Treatment choice is difficult as little information is available in the literature. In such situations, clinicians will base treatment decisions on retrospective data or case report series with a lower scientific level of evidence than that obtained from randomised controlled clinical trials. The only way forward is clinical trials organisation, but to perform it within rare indications we are always faced with many methodological, regulatory, and organisational challenges, besides stakeholders’ different views, which are not usually concurrent. The aims of the European Organisation for Research and Treatment of Cancer (EORTC) are to develop, conduct, coordinate, and stimulate translational and clinical research in Europe to improve the management of cancer and related problems by increasing survival but also patient quality of life. In particular, extensive and comprehensive research in the field of rare cancers is beyond the means of individual European hospitals and can be best accomplished through the multidisciplinary multinational efforts of basic scientists and clinicians. In this paper, we will present an overview of the clinical research scene for rare cancers and will try to propose possible steps to improve the current situation.

A systematic literature review of evidence-based clinical practice for rare diseases: what are the perceived and real barriers for improving the evidence and how can they be overcome?

“…This problem resides in the difficulty to diagnose RDs, to record diseases, and to trace RD patients [ 28 ]. This is due in part to the scarce knowledge about these diseases, and to the fact that far from all countries have efficient processes for referral [ 29 ], resulting in significant delays in diagnosis. RD patients often remain undiagnosed even in the best conditions of expertise due to lack of knowledge about natural history or clinical signs and symptoms.…”

“…Biomarker development is one source for potential surrogate outcomes. FDA and EMA orphan drug regulations contemplate approval of drugs for which the benefits for patients with unmet medical needs are based on reasonable evidence, often based on surrogate outcomes, that should demonstrate their clinical benefit during post-marketed studies [ 29 ]. Such ‘adaptive’ pathways and procedures seem to have their special problems making them less attractive or outright dangerous to patients [ 21 , 70 ].…”

Center with or Without a Coordinator? The Coordinator as an Integral Part of a Research Team

“…The EORTC CRC Group focuses particularly on elevating the competencies of coordinators along the path of cancer patients, emphasizing comprehensive support during oncology patients' participation and meticulous study execution in alignment with the protocol. 21 Among clinical trial participants, a prevalent term to describe coordinators is "the attorney" Coordinators are seen as attorneys for the patients involved, despite the complexities this role entails when it comes to assisting with decisions that ultimately rest with the trial participant. Patients tend to seek the coordinator's advice and anticipate both logistical and personal backing.…”

Conducting non-commercial international clinical trials: the ICR-CTSU experience

“…In the era of precision medicine and with priority placed on developing new treatments for rare cancers, the need for international participation in academic clinical trials is increasing. However, lack of harmonisation of international legal, ethical and financial systems can make this challenging and the cost and effort of conducting trials internationally can be considered prohibitive, particularly where the sample size is comparatively small [ 1 – 5 ]. In this article we describe the progress, success and challenges faced by a UK-based, academic clinical trials unit, The Institute of Cancer Research – Clinical Trials and Statistics Unit (ICR-CTSU) to manage academically sponsored non-commercial international clinical trials.…”