IMPROVING PEDIATRIC DRUG SAFETY: NEED FOR MORE EFFICIENT CLINICAL TRANSLATION OF PHARMACOVIGILANCE KNOWLEDGE
Main Article Content
Keywords
Pediatric drug safety, pharmacovigilance, surveillance, adverse drug reactions, knowledge translation, risk communication
Abstract
There is urgency to improve the evaluation of pediatric drug safety in the pre-market and post-market phases of drug evaluation. The need to improve pharmacovigilance methods concerns not only new drugs but also existing drugs that have been used for many years in an off-label manner in children. Effective methods for early detection of adverse drug reactions (ADRs) and drug safety epidemiologic studies are a pressing need in pediatrics. Moreover, the nature and severity of an ADR as well as the extent to which the suspected drug is being used, will determine how quickly the information about risk needs to be made available to users and what would be the most appropriate method of communication. Based on our experience through the Genotype-specific Approaches to Therapy in Children study, an active ADR surveillance network of pediatric hospitals across Canada, we present five strategic elements that should be included in pharmacovigilance initiatives in pediatrics: active ADR surveillance; drug or ADR targeted pharmacovigilance; trained surveillance clinicians; case-control methodology and standardized procedures for recognition; reporting and evaluating drug-induced harm. In addition, linking pharmacovigilance with pharmacogenomics to find drug safety solutions is presented as a promising strategy for knowledge generation. Finally, we discuss the importance of an efficient translation of the pharmacovigilance knowledge into clinical practice to achieve safer drug therapy in children.
References
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33. Edwards IR. What are the real lessons from Vioxx®? Drug Safety 2005; 28(8): 651-658.
34. Hauben M, Aronson JK. Defining “signal” and its subtypes in pharmacovigilance based on a systematic review of previous definitions. Drug Saf 2009; 32(2): 99-110.
35. Kalow W, Tang BK, Endrenyi L. Hypothesis: comparisons of inter- and intra-individual variations can substitute for twin studies in drug research. Pharmacogenetics 1998; 8(4):283-289.
36. Impicciatore M. Pharmacogenomic can give children safer medicines. Arch Dis Child 2003;88(4):366.
37. Jaja C, Rothstein M. Pharmacogenomics: Social, Ethical, and Clinical Dimensions. New York: John Wiley and Sons, Inc., 2003.
38. Kling J. US FDA contemplates collection of pharmacogenomic data. Nat Biotechnol 2003;21(6):590.
39. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277(4):301- 306.
40. Joly Y, Sillon G, Silverstein T, Krajinovic M, Avard D. Pharmacogenomics: Don’t forget the children. Current Pharmacogenomics and Personalized Medicine 2008; 6: 77-84.
41. Howland RH. Pharmacogenetics and Pharmacovigilance. Drug Saf 2009; 32(3): 265- 270.
42. Bérard A, Azoulay L. Koren G, Blais L, Perreault S, Oraichi D. Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol 2007; 63: 196- 205.
43. Aronson JK. Adverse drug reactions – no farewell to harms. Br J Clin Pharmacol 2007; 63(2): 131- 135.
44. Kanelleas AI, Thornton S, Berth-Jones J. Suggestions for effective contraception in isotretinoin therapy. Br J Clin Pharmacol 2008; 67(1): 137-138.
45. Van Puijenbroek E, Conemans J, Van Grootheest K. Spontaneous reports and pharmacogenetics. The role of the pharmacovigilance centre. Drug Saf 2009; 32(4): 357-358.
46. Leeder JS. Developmental and pediatric pharmacogenomics. Pharmacogenomics 2003; 4: 331-341.
47. The Erice Manifesto. For global reform of the safety of medicines in patient care. Drug Safety 2007; 30(3): 187-190.
2. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329(7456): 15-9.
3. Rzany B, Mockenhaupt M, Baur S, Schroder W, Stocker U, Mueller J, Hollander N, Bruppacher R, Schopf E. Epidemiology of erythema exsudativum multiforme majus, Stevens- Johnson syndrome, and toxic epidermal necrolysis in Germany (1990-1992): structure and results of a population-based registry. J Clin Epidemiol 1996; 49(7):769-73.
4. Mittmann N, Knowles SR, Gomez M, Fish JS, Cartotto R, Shear NH. Evaluation of the extent of under-reporting of serious adverse drug reactions: the case of toxic epidermal necrolysis. Drug Saf 2004; 27(7):477-87.
5. Committee on the Assessment of the US Drug Safety System, Alina Baciu, Kathleen Stratton, Sheila P. Burke, Editors. The Future of Drug Safety: Promoting and Protecting the Health of the Public. The National Academies Press: Washington, D.C. 2007.
6. World Health Organization (WHO). The importance of pharmacovigilance – Safety monitoring of medicinal products. Geneva: WHO, 2002.
7. Therapeutics Initiative, University of British Columbia. Rofecoxib (Vioxx®) withdrawal generates uncertainty about “COX-2s.” Do product monographs adequately inform? Therapeutics Letter 2004 (July-October); 53.
8. National Institute of Child Health and Human Development. Pediatric Pharmacology Research Unit (PPRU) Network [online]. Available from: http://www.nichd.nih.gov/research/supported/pp ru1.cfm. Accessed 2009 Jun 24.
9. MacLeod S, Peterson R, Wang Y, Li Z, Gui Y, Schaller J. Challenges in international pediatric pharmacology. A milestone meeting in Shanghai. Pediatr Drugs 2007; 9(4): 215-218.
10. Uppsala Monitoring Centre (UMC) Safety Monitoring of Medicinal Products. Guidelines for setting up and running a Pharmacovigilance Centre. Uppsala: UMC, 2000.
11. The Uppsala Monitoring Centre. WHO Collaborating Centre for International Drug Monitoring. WHO Programme. Available from: http://www.whoumc. org/DynPage.aspx?id=13140&mn=1514#4. Accessed 2009 Jun 24.
12. Etwel FA, Rieder MJ, Bend JR, Koren G. A surveillance method for the early identification of idiosyncratic Adverse Drug Reactions. Drug Safety 2008; 31(2): 169-180.
13. Berkovitch M, Pope E, Phillips J, Koren G. Pemoline-associated fulminant liver failure: Testing the evidence for causation. Clin Pharmacol Ther 1995; 57: 696-8.
14. Paolucci P, Pritchard-Jones K, Cano-Garcinuno MC, Catapano M, Iolascon A, Ceci A. Challenges in prescribing drugs for children with cancer. Lancet Oncol 2007; 9:176-83.
15. Canadian Cancer Society’s Steering Committee: Canadian Cancer Statistics 2009. Toronto: Canadian Cancer Society, 2009.
16. Sankila R, Martos Jiménez MC, Miljus D, Pritchard-Jones K, Steliarova-Foucher E, Stiller C. Geographical comparison of cancer survival in European children (1988-1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42(13): 1972-80.
17. Grégoire F, Pariente A, Fourrier-Reglat A, Haramburu F, Bégaud B, Moore N. A signal of increased risk of hypoglycaemia with angiotensin receptor blockers caused by confounding. Br J Clin Pharmacol 2008; 66(1): 142-145.
18. Ross CJ, Carleton B, Warn DG, Stenton SB, Rassekh SR, Hayden MR. Genotypic approaches to therapy in children: a national active surveillance network (GATC) to study the pharmacogenomics of severe adverse drug reactions in children. Annals of the New York Academy of Sciences 2007; 1110: 177-92.
19. Carleton BC, Poole RL, Smith MA, Leeder JS, Ghannadan R, Ross CJD, Phillips MS, Hayden MR. Adverse drug reaction active surveillance: developing a national network in Canada’s children’s hospitals. Pharmacoepidemiol Drug Saf 2009;18(8):713-21.
20. Menniti-Ippolito F, Raschetti R, Da Cas R, Giaquinto C, Cantarutti L, for the Italian Pediatric Pharmacosurveillance Multicenter Group. Active monitoring of adverse drug reactions in children. Lancet 2000; 355:1613-14.
21. Carleton BC, Smith MA, Gelin MN, Heathcote SC. Paediatric adverse drug reaction reporting: understanding and future directions. Can J Clin Pharmacol 2007; 14(1): e45-e57.
22. Carleton B, Lesko A, Milton J, Poole RL. Active surveillance systems for pediatric adverse drug reactions: an idea whose time has come. Current Therapeutic Research 2001; 62(10): 738-742.
23. Lexchin J. Is there still a role for spontaneous reporting of adverse drug reactions? CMAJ 2006; 174(2): 191-192.
24. De Langen J, Van Hunsel F, Passier A, De Jongvan den Berg L, Van Grootheest K. Adverse drug reaction reporting by patients in the Netherlands. Three years of experience. Drug Saf 2008; 31 (6): 515-524.
25. Blenkinsopp A, Wilkie P, Wang M, Routledge PA. Patient reporting of suspected adverse drug reactions: a review of published literature and international experience. Br J Clin Pharmacol 2006; 63(2): 148-156.
26. Johann-Liang R, Wyeth J, Chen M, Cope JU. Pharmacoepidemiology and Drug Safety 2009; 18: 24-27.
27. Impicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C, Bonati M. Incidence of adverse drug reactions in paediatric in/out-patients: a systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol 2001; 52: 77-83.
28. Schaefer C, Ornoy A, Clementi M, Meister R, Weber-Schoendorfer C. Using observational cohort data for studying drug effects on pregnancy outcome–Methodological considerations. Reprod Toxicol 2008; 26: 36-41.
29. Motherisk - Treating the mother – protecting the unborn. The Hospital for Sick Children (SickKids). Toronto, Canada. Available from: http://www.motherisk.org. Accessed June 30, 2009.
30. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet 2000; 356: 1255-59.
31. Levi N, Bastuji-Garin S, Mockenhaupt M, Roujeau JC, Flahault A, Kelly JP, Martin E, Kaufman DW, Maison P. Medications as risk factors of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Children: A pooled Analysis. Pediatrics 2009; 123: e297-e304.
32. Hasford J, Goettler M, Munter K-H, Muller- Oerlinghausen B. Physician´s knowledge and attitudes regarding the spontaneous reporting system for adverse drug reactions. J Clin Epidemiol 2002; 55: 945-950.
33. Edwards IR. What are the real lessons from Vioxx®? Drug Safety 2005; 28(8): 651-658.
34. Hauben M, Aronson JK. Defining “signal” and its subtypes in pharmacovigilance based on a systematic review of previous definitions. Drug Saf 2009; 32(2): 99-110.
35. Kalow W, Tang BK, Endrenyi L. Hypothesis: comparisons of inter- and intra-individual variations can substitute for twin studies in drug research. Pharmacogenetics 1998; 8(4):283-289.
36. Impicciatore M. Pharmacogenomic can give children safer medicines. Arch Dis Child 2003;88(4):366.
37. Jaja C, Rothstein M. Pharmacogenomics: Social, Ethical, and Clinical Dimensions. New York: John Wiley and Sons, Inc., 2003.
38. Kling J. US FDA contemplates collection of pharmacogenomic data. Nat Biotechnol 2003;21(6):590.
39. Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277(4):301- 306.
40. Joly Y, Sillon G, Silverstein T, Krajinovic M, Avard D. Pharmacogenomics: Don’t forget the children. Current Pharmacogenomics and Personalized Medicine 2008; 6: 77-84.
41. Howland RH. Pharmacogenetics and Pharmacovigilance. Drug Saf 2009; 32(3): 265- 270.
42. Bérard A, Azoulay L. Koren G, Blais L, Perreault S, Oraichi D. Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol 2007; 63: 196- 205.
43. Aronson JK. Adverse drug reactions – no farewell to harms. Br J Clin Pharmacol 2007; 63(2): 131- 135.
44. Kanelleas AI, Thornton S, Berth-Jones J. Suggestions for effective contraception in isotretinoin therapy. Br J Clin Pharmacol 2008; 67(1): 137-138.
45. Van Puijenbroek E, Conemans J, Van Grootheest K. Spontaneous reports and pharmacogenetics. The role of the pharmacovigilance centre. Drug Saf 2009; 32(4): 357-358.
46. Leeder JS. Developmental and pediatric pharmacogenomics. Pharmacogenomics 2003; 4: 331-341.
47. The Erice Manifesto. For global reform of the safety of medicines in patient care. Drug Safety 2007; 30(3): 187-190.