N-of-1 Trials in Pediatric Oncology: From a Population-Based Approach to Personalized Medicine—A Review

Abstract

Pediatric oncology is a critical area where the more efficient development of new treatments is urgently needed. The speed of approval of new drugs is still limited by regulatory requirements and a lack of innovative designs appropriate for trials in children. Childhood cancers meet the criteria of rare diseases. Personalized medicine brings it even closer to the horizon of individual cases. Thus, not all the traditional research tools, such as large-scale RCTs, are always suitable or even applicable, mainly due to limited sample sizes. Small samples and traditional versus subject-specific evidence are both distinctive issues in personalized pediatric oncology. Modern analytical approaches and adaptations of the paradigms of evidence are warranted. We have reviewed innovative trial designs and analytical methods developed for small populations, together with individualized approaches, given their applicability to pediatric oncology. We discuss traditional population-based and individualized perspectives of inferences and evidence, and explain the possibilities of using various methods in pediatric personalized oncology. We find that specific derivatives of the original N-of-1 trial design adapted for pediatric personalized oncology may represent an optimal analytical tool for this area of medicine. We conclude that no particular N-of-1 strategy can provide a solution. Rather, a whole range of approaches is needed to satisfy the new inferential and analytical paradigms of modern medicine. We reveal a new view of cancer as continuum model and discuss the “evidence puzzle”.

Individual Treatment Trials—Do Experts Know and Use This Option to Improve the Treatability of Mucopolysaccharidosis?

“…ITTs are an increasingly recommended option to improve treatability in different settings of high unmet medical needs, including oncology and osteoarthritis [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. However, all publications report underutilization of this promising option [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. To the best of our knowledge, our study is the first which systematically assesses the actual utilization of and barriers to ITTs in a specific indication.…”

Advanced Molecular Characterisation in Relapsed and Refractory Paediatric Acute Leukaemia, the Key for Personalised Medicine

“…All new therapies should ideally be administered within the context of clinical trials [ 53 ]. However, trials are not always available for patients, and several other limitations, such as eligibility criteria, must be considered [ 54 ]. Due to this limitation, its use depends, on many occasions, upon compassionate, off-label or extended use prescriptions, with the consequent safety and efficacy concerns.…”

Developing a Preclinical Nurse-Nurse Communication Framework for Clinical Trial Patient-Related Safety Information

“…28 Commonly used for high-risk cancers and rare diseases, personalized N-of-1 trials support longer-term participant exposure and involvement on a clinical trial. 28 The extended exposure and participation on a clinical trial coupled with more precise dosing of an investigational product leave clinical providers without standardized resources to retrieve information pertaining to patient care guidance. Specialties such as emergency care, where there is a narrow margin for nurse or provider decision-making error, benefit from the preclinical communication framework.…”

“…The personalization of clinical trials means that safety profiles of investigational products are becoming more individualized and not readily generalizable for provider drug databases 28 . Commonly used for high-risk cancers and rare diseases, personalized N-of-1 trials support longer-term participant exposure and involvement on a clinical trial 28 .…”

“…The personalization of clinical trials means that safety profiles of investigational products are becoming more individualized and not readily generalizable for provider drug databases 28 . Commonly used for high-risk cancers and rare diseases, personalized N-of-1 trials support longer-term participant exposure and involvement on a clinical trial 28 . The extended exposure and participation on a clinical trial coupled with more precise dosing of an investigational product leave clinical providers without standardized resources to retrieve information pertaining to patient care guidance.…”