• Sharwankumar Singhal Cadila Pharmaceuticals Ltd., Ahmedabad, IndiaDepartment of Pharmaceutical Analysis, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Chandlodia, Gota, Ahmedabad, Gujarat, India
  • Bhaswat Chakraborty Nirma University


Cisplatin, Carboplatin, Signal detection, Ototoxicity, Pruritis


Objective: The objective of the study was to identify possible toxic signal induced by cisplatin and carboplatin treatment by searching database from Canadian Adverse Reaction Monitoring Program (CADRMP). 

Methods: Adverse drug reaction (ADR) signal detection were measured by methods such as, the proportional reporting ratio (PRR); reporting odds ratio (ROR); the chi-square statistics method; the 95% confidence interval (CI); the observed to expected (O/E) ratio and Du Mouchel method calculated PRR. Signal detection was also performed by applying Bayesian Confidence Propagation Neural Network Method (BCPNN). Calculated statistics by different methods were compared with regulatory criteria of a statistics value ≥ 4.0 for chi-square statistics and ≥3.0 for the rests for signal detection to be declared as significant.

Results: For cisplatin, the PRR was found to be 53.44; by the Du Mouchel Method it was 20.7977; the chi-square statistics was 544.70, whereas the lower and upper limits of 95% CI of PRR was found to be 4.57 and 3.67, respectively. The O/E ratio was found to be 20.9130 and ROR was found to be 55.03. For carboplatin, the PRR was found to be 7.04412; by the Du Mouchel Method it was 16.4360; the chi-square statistics were 623.36645, whereas the lower and upper limits of 95% CI of PRR was found to be 3.6475 and 2.9167, respectively. The O/E ratio was found to be 16.43854 and reporting odds ratio was found to be 7.6065. By BCPNN method, the value of information components (IC) is 4.4031 for cisplatin means middle signal for cisplatin-induced ototoxicity. However, the value of IC is 2.4851 for carboplatin means middle signal for pruritis.

Conclusion: The therapeutic class specific signal of ototoxicity coupled with cisplatin and of pruritis coupled with carboplatin was found significant enough to induce ototoxicity and pruritis respectively in the Canadian population.



Download data is not yet available.


World Health Organization Fact sheet. 2013. Available from: http://www.who.int/mediacentre/factsheets/fs297/en/# [Last accessed 15 Apr 2013].

Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 2008;25:2097–116.

Connie Henke Yarbro. Carboplatin: A clinical review. Seminars Oncology Nursing 1989;5:63–9.

Lokich J, Anderson N. Carboplatin versus cisplatin in solid tumors: an analysis of the literature. Annals of Oncology 1998;9:13-21.

Sakaeda T, Kadoyama K, Okuno Y. Adverse event profiles of platinum agents: data mining of the public version of the FDA adverse event reporting system, AERS, and reproducibility of clinical observations. Int J Med Sci 2011;8:487-91.

Harpaz R, DuMouchel W, LePendu P, Bauer-Mehren A, Ryan P, Shah NH. Performance of pharmacovigilance signal-detection algorithms for the FDA adverse event reporting system. Clin Pharmacol Ther 2013;93:539-46.

Health Canada. Available from: http://www.hc-sc.gc.ca/index-eng. php. [Last accessed 15 Apr 2013].

Norén GN. Statistical methods for knowledge discovery in adverse drug reaction surveillance typeset by LATEX, Department of Mathematics, Stockholm University, Stockholm; 2007. p. 1–41. Available from: http://www.diva-portal.org/smash/get/diva2:197004/FULLTEXT01.pdf

Eudravigilance Expert Working Group (EV-EWG), European Medicine Agency Guidelines, London; 2006. p. 1-22.

Health Canada. Canadian adverse event reporting program. Available from: Http://www.CADRMP/index_e.jsp.

Bate A, Lindquist M, Edwards IR, Orre R. A data mining approach for signal detection and analysis. Drug Saf 2002;25:393-7.

Health Canada. Canadian adverse event reporting program. Available from: www.hc-sc.gc.ca/ahc-asc/activit/atip-aiprp/priv-prot/pia-efvp-a-eng.php

Evans SJ, Waller PC, Davis S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf 2001;10:483-6.

Van Puijenbroek EP, Bate A, Leufkens HG, Lindquist M, Orre R, Egberts AC. A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiol Drug Saf 2002;11:3-10.

Bate A, Lindquist M, Edwards IR, Olsson S, Orre R, Lansner A, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol 1998;54:315-21.

Szarfman A, Machado SG, O’Neill RT. Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the US FDA’s spontaneous reports database. Drug Saf 2002;25:381-92.

Bate A, Evans SJ. Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf 2009;18:427-36.

Gould AL. Practical pharmacovigilance analysis strategies. Pharmacoepidemiol Drug Saf 2003;12:559-74.

Almenoff JS, Pattishall EN, Gibbs TG, DuMouchel W, Evans SJ, Yuen N. Novel statistical tools for monitoring the safety of marketed drugs. Clin Pharmacol Ther 2007;82:157-66.

Surendiran A, Balamurugan N, Gunaseelan K, Akhtar S, Reddy KS, Adithan C. Adverse drug reaction profile of cisplatin-based chemotherapy regimen in a tertiary care hospital in India: An evaluative study. Indian J Pharmacol 2010;42:40-3.

European Medicine Agency: Pharmacovigilance working party (PhVWP). plenarymeeting. Cisplatin–Risk of increased ototoxicity in patients with genetic variants of TMPT and COMT. 2010. Available from: http://www.ema.europa.eu/ htms/human/phv/reports.htm

Whitehorn H, Sibanda M, Lacerda M, Spracklen T, Ramma L, Dalvie S, et al. High prevalence of cisplatin-induced ototoxicity in Cape Town, South Africa. S Afr Med J 2014;104:288-91.

Kadoyama K, Kuwahara A, Yamamori M, Brown JB, Sakaeda T, Okuno Y. Hypersensitivity reactions to anticancer agents: Data mining of the public version of the FDA adverse event reporting system, AERS. J Exp Clin Cancer Res 2011;30:93-8.

Paraplatin: Product Monograph. Available from: http://www.fda.gov/ohrms/dockets/ac/05/briefing/20054180b_03_05_Carboplatin%20label%201-9-04%20FDA.pdf

Maurie M, Kennedy A, Webster K, Elson P, Peterson G, Kulp B, et al. Clinical Features of hypersensitivity reactions to carboplatin. J Clin Oncol 1999;17:1141-5.



How to Cite

Singhal, S., and B. Chakraborty. “EVALUATION OF SIGNAL DETECTION FOR PLATINUM COMPOUNDS IN CANADIAN SPONTANEOUS ADVERSE EVENT REPORTS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 6, June 2015, pp. 405-11, https://innovareacademics.in/journals/index.php/ijpps/article/view/5025.



Original Article(s)