title: Modern clinical research: How rapid learning health care and cohort multiple randomised clinical trials complement traditional evidence based medicine.
abstract: BACKGROUND
  Trials are vital in informing routine clinical care; however, current designs have major deficiencies. An overview of the various challenges that face modern clinical research and the methods that can be exploited to solve these challenges, in the context of personalised cancer treatment in the 21st century is provided.
  
  
  OBJECTIVE
  The purpose of this manuscript, without intending to be comprehensive, is to spark thought whilst presenting and discussing two important and complementary alternatives to traditional evidence-based medicine, specifically rapid learning health care and cohort multiple randomised controlled trial design. Rapid learning health care is an approach that proposes to extract and apply knowledge from routine clinical care data rather than exclusively depending on clinical trial evidence, (please watch the animation: http://youtu.be/ZDJFOxpwqEA). The cohort multiple randomised controlled trial design is a pragmatic method which has been proposed to help overcome the weaknesses of conventional randomised trials, taking advantage of the standardised follow-up approaches more and more used in routine patient care. This approach is particularly useful when the new intervention is a priori attractive for the patient (i.e. proton therapy, patient decision aids or expensive medications), when the outcomes are easily collected, and when there is no need of a placebo arm.
  
  
  CONCLUSIONS
  Truly personalised cancer treatment is the goal in modern radiotherapy. However, personalised cancer treatment is also an immense challenge. The vast variety of both cancer patients and treatment options makes it extremely difficult to determine which decisions are optimal for the individual patient. Nevertheless, rapid learning health care and cohort multiple randomised controlled trial design are two approaches (among others) that can help meet this challenge.
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Zindler
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: Vanneste
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Lien
authors.initials: L
authors.lastname: van de Voorde
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Jacobs
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Eekers
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Peerlings
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Reymen
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Ruben T H M
authors.initials: RT
authors.lastname: Larue
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Timo M
authors.initials: TM
authors.lastname: Deist
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Evelyn E C
authors.initials: EE
authors.lastname: de Jong
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Aniek J G
authors.initials: AJ
authors.lastname: Even
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Adriana J
authors.initials: AJ
authors.lastname: Berlanga
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Roelofs
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Ralph T H
authors.initials: RT
authors.lastname: Leijenaar
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Catharina M L
authors.initials: CM
authors.lastname: Zegers
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Evert
authors.initials: E
authors.lastname: van Limbergen
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Berbee
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: van Elmpt
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Cary
authors.initials: C
authors.lastname: Oberije
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: Houben
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Andre
authors.initials: A
authors.lastname: Dekker
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Boersma
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Verhaegen
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Bosmans
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Hoebers
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Smits
authors.affiliation: a Department of Radiation Oncology (MAASTRO) , GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Sean
authors.initials: S
authors.lastname: Walsh
mesh_terms: D019317:Evidence-Based Medicine / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D057285:Precision Medicine / Q000379:methods*; D016032:Randomized Controlled Trials as Topic