title: Communicating BRCA research results to patients enrolled in international clinical trials: lessons learnt from the AGO-OVAR 16 study.
abstract: The focus on translational research in clinical trials has the potential to generate clinically relevant genetic data that could have importance to patients. This raises challenging questions about communicating relevant genetic research results to individual patients.
  
  
  
  An exploratory pharmacogenetic analysis was conducted in the international ovarian cancer phase III trial, AGO-OVAR 16, which found that patients with clinically important germ-line BRCA1/2 mutations had improved progression-free survival prognosis. Mechanisms to communicate BRCA results were evaluated, because these findings may be beneficial to patients and their families.
  
  
  
  Communicating individual BRCA results was not anticipated during clinical trial design. Consequently, options were not available for patients to indicate their preference for receiving their individual results when they signed pharmacogenetic informed consent. Differences in local requirements, clinical practice, and opinion regarding the ethical aspects of how to convey genetic results to patients are all potential barriers to returning individual BRCA results to patients. Communicating the aggregate BRCA result from this study provided clinical investigators with a mechanism to disseminate the overall study finding to patients while taking individual circumstances, local guidelines and clinical practice into account.
  
  
  
  This study illustrates the importance of increasing the clarity and scope of informed consent and the need for patient engagement to ensure clinical trial participants can indicate their preference regarding receipt of potentially important individual pharmacogenetic results.
  
  
  
  This study was registered in the NCT Clinical Trial Registry under NCT00866697 on March 19, 2009, following approval from participating ethics committees (Additional file 1).
authors: GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK. david.x.pulford@gsk.com.
authors: David J
authors: DJ
authors: Pulford
authors: AGO Study group and Department of Gynecology & Gynecologic Oncology, Kliniken Essen Mitte (KEM), Essen, Germany.
authors: Philipp
authors: P
authors: Harter
authors: GINECO and Medical Oncology, Institut Bergonié, Bordeaux, France.
authors: Anne
authors: A
authors: Floquet
authors: GSK Stockley Park West, 1-3 Iron Bridge Road, Uxbridge, UK.
authors: Catherine
authors: C
authors: Barrett
authors: Department of Obstetrics & Gynecology, KGOG and Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea.
authors: Dong Hoon
authors: DH
authors: Suh
authors: ANZGOG and The Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia.
authors: Michael
authors: M
authors: Friedlander
authors: GEICO and Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: José Angel
authors: JA
authors: Arranz
authors: JGOG and Saitama Medical University International Medical Center, Hidaka, Japan.
authors: Kosei
authors: K
authors: Hasegawa
authors: GlaxoSmithKline Research and Development, Philadelphia, USA.|Immuno-Oncology Development, Incyte Corporation, Wilmington, DE, USA.
authors: Hiroomi
authors: H
authors: Tada
authors: BGOG and Medical Oncology, Université Catholique de Louvain, CHU UCL Namur, Belgium.
authors: Peter
authors: P
authors: Vuylsteke
authors: NSGO and Rigshospitalet, Copenhagen, Denmark.
authors: Mansoor R
authors: MR
authors: Mirza
authors: MaNGO and Ospedale Filippo del Ponte, Varese, Italy.
authors: Nicoletta
authors: N
authors: Donadello
authors: Department of Woman Health, MITO and Catholic University of the Sacred Heart, Rome, Italy.
authors: Giovanni
authors: G
authors: Scambia
authors: GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
authors: Toby
authors: T
authors: Johnson
authors: GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
authors: Charles
authors: C
authors: Cox
authors: Palo Alto Medical Foundation, San Francisco, CA, USA.
authors: John K
authors: JK
authors: Chan
authors: Karl Landsteiner Research Institute and Department of Obstetrics and Gynecology, General Public Teaching Hospital, Korneuburg, Vienna, Austria.
authors: Martin
authors: M
authors: Imhof
authors: NYGOG and University of Cincinnati Cancer Institute, Cincinnati, OH, USA.
authors: Thomas J
authors: TJ
authors: Herzog
authors: Cancer Trials Ireland, 60 Fitzwilliam Square N, Dublin 2, Ireland.
authors: Paula
authors: P
authors: Calvert
authors: AGO Germany and Department of Gynecology and Obstetrics, TU Dresden, Carl-Gustav-Carus University, Dresden, Germany.
authors: Pauline
authors: P
authors: Wimberger
authors: GINECO and ICO Centre René Gauducheau, Saint-Herblain, France.
authors: Dominique
authors: D
authors: Berton-Rigaud
authors: KGOG, Gynecologic Cancer Branch and Center for Uterine Cancer, National Cancer Center, Goyang, Korea.
authors: Myong Cheol
authors: MC
authors: Lim
authors: AGO Study Group, Wiesbaden, Germany.
authors: Gabriele
authors: G
authors: Elser
authors: GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
authors: Chun-Fang
authors: CF
authors: Xu
authors: AGO Study group and Department of Gynecology & Gynecologic Oncology, Kliniken Essen Mitte (KEM), Essen, Germany.
authors: Andreas
authors: A
authors: du Bois
mesh_terms: D022126:Access to Information; D019313:BRCA1 Protein / Q000235:genetics*; D030881:Disclosure / Q000941:ethics; D005260:Female; D006801:Humans; D007258:Informed Consent; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*; D057240:Patient Preference; D011379:Prognosis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human
keywords: BRCA mutation; Bioethics; Incidental finding; Ovarian cancer; Pharmacogenetic research