Estimation of theoretical cost preventability achievable with an effective pharmacovigilance activity in a Pharmacovigilance

Regional Centre in Italy

Alice Capogrosso Sansone Department of Clinical and Experimental Medicine, University of Pisa, Italy

28 October 2015 Parallel session D - Benefit/Burden of pharmacovigilance

•  Adverse drug reactions (ADRs) are common causes of morbidity and mortality.

•  In Europe, it has been estimated that approximately 4% of all hospital admissions are caused by an ADR, and up to 10% of hospitalized patients experience an ADR during their stay.

•  ADR-related admissions are preventable up to 50%, varying by ADR category and seriousness.

•  In addition to their impact on human health, ADRs also have significant impact on healthcare direct costs, owing to hospitalization and treatment costs.

•  The main issue of ADRs in health care is to know how to optimize the costs of ADRs, aiming at finding the right balance between costs and benefits.

Introduction

Bouvy JC et al. Drug Saf. 2015;38:437-53

Lundkvist J and Jönsson B. Fundam Clin Pharmacol. 2004;18:275-80

Nivya K et al. Saudi Pharm J. 2015;23:1-8

Recently, social and healthcare costs related to ADRs have become a relevant issue, and they are increasingly being included in budget estimations for health resource allocations.

Aim of the study

1)  Estimation of the mean cost of an ADR and the rate of preventable ADRs, by reviewing studies evaluating ADR-related costs.

2)  Estimation of the presumed ADR-related cost savings within a regional healthcare system.

Rodríguez-Monguió R et al. Pharmacoeconomics. 2003;21:623-50

How does an ADR cost?

1) Estimation of the mean cost of an ADR and the rate of preventable ADRs

Selection of studies

•  A systematic review of English medical literature quoted in PUBMED (January 2005-March 2015) was conducted.

•  Inclusion criteria: all studies performed in developed countries, evaluating direct costs of ADRs, for which the mean cost of an ADR (serious and/or not-serious) could be estimated.

•  Exclusion criteria: studies on specific side-effects or drug-classes.

Data extraction

For each study the following data were extracted: mean cost of serious and/or not-serious ADRs, % of preventable ADRs.

Data analysis

•  mean cost (95% confidence interval - CI) for single ADR (serious and/or not-serious)

•  mean percentage (95% CI) of preventable ADRs

Both endpoints were calculated using data from all included studies and from studies expressing costs in Euros only.

Methods

Methods 2) Estimation of the presumed ADR-related cost savings within a regional healthcare system

- Extraction of the spontaneous ADR reports in Tuscany from the Italian Pharmacovigilance Network system in 2014 •  Total number of serious ADRs

•  Total number of not-serious ADRs

- Estimation of total ADR-related costs and preventable ADR-related costs in Tuscany (using data from studies expressing costs in Euros only)

•  Overall cost and cost/million-inhabitants of serious and not-serious ADRs •  Overall cost and cost/million-inhabitants of preventable ADRs

- Estimation of the range of costs/million-inhabitants (95% CI) •  Range costs of serious and not-serious ADRs •  Range costs of preventable ADRs

- Sensitivity analysis •  For range cost estimations, intervals were varied by up to 50% in each direction

Bocci G et al. Ann Oncol. 2005;16:1243-52

Results

Literature search results Number of articles: 1381

Number of studies included in the analysis (13):

- 13 studies on serious ADRs - 3 studies on not-serious ADRs - 8 studies on preventable ADRs

Excluded articles (1367):

- reviews (426) - cost effectiveness studies (61) - studies in emerging countries (70)

- studies on side effects of specific drugs or drug classes (182) - studies in language other than English (167) - other reasons (462)

1) Estimation of the mean cost of an ADR and the rate of preventable ADRs

Characteristics and main data of the included studies Reference Country Age Setting Preventable

ADRs (%) Cost of

serious ADR Cost of

not-serious ADR

Field et al., 2005 USA Elderly Ambulatory clinic site 30% $ 1,310 $ 325

Bond et al., 2006 USA All ages Hospital 53% $ 2,620 n.a.

Nuckols et al., 2008 USA All ages Intensive care 28% $ 6,835 n.a.

Shamliyan, 2010 USA Elderly Hospital n.a. $ 16,599 n.a.

Wu et al., 2012 Canada Elderly ED n.a. $ 8,220 $ 235

Gallagher et al., 2012 United Kingdom Pediatric patients Hospital 96% £ 4,753 n.a.

Hoonhout et al., 2010 Netherlands All ages Hospital 41% € 2,507 n.a

Carrasco-Garrido et al., 2010 Spain All ages Hospital n.a. € 4,382 n.a.

Leendertse et al., 2011 Netherlands Adults Hospital 46% € 5,461 n.a.

Pérez Menéndez-Conde et al., 2011 Spain Adults Hospital 65% € 4,844 n.a.

Rottenkolber et al., 2012 Germany All ages Hospital n.a. € 2,948 n.a.

Perrone et al., 2014 Italy All ages ED 42% € 1,166 € 82

Meier et al., 2015 Germany All ages ED 61% € 2,743 n.a.

ADR: adverse drug reaction; ED: emergency department; USA: United States of America

Estimated costs and preventable ADRs

Mean cost of a serious ADR

(95% CI)

Mean cost of a not-serious ADR

(95% CI)

Mean % of preventable ADRs

(95% CI)

Overall studies € 9,352 (6,439 - 12,264) € 143 (77 - 209) 51% (38 - 65)

Studies (costs in €) € 4,127 (3,522 - 4,732) € 82 (57 - 107) 51% (41 - 61)

ADRs: adverse drug reaction; CI: confidence interval

Results 1) Estimation of the mean cost of an ADR and the rate of preventable ADRs

Number of total, serious, not-serious and preventable ADRs in Tuscany in 2014

Results 2) Estimation of the presumed ADR-related cost savings within a regional healthcare system

4,495

1,498

2,997 2,292

(1,843 - 2,742)

0 500

1000 1500 2000 2500 3000 3500 4000 4500 5000

Total ADRs Serious ADRs Not-serious ADRs Estimated preventable ADRs

Presumed cost of serious, not-serious and preventable ADRs in Tuscany in 2014 Overall cost

in euros Cost/million-inhabitants

in euros

Range of costs/million-inhabitants in euros

(95% CI)

Range of costs/million-inhabitants in euros (sensitivity analysis)

Serious ADRs 6,182,275 1,669,012 1,424,232 - 1,913,792 712,116 - 2,870,689

Not-serious ADRs 245,754 66,346 46,442 - 86,249 23,221 - 129,374

Total ADRs 6,428,029 1,735,358 1,470,674 - 2,000,042 735,337 - 3,000,063

Preventable ADRs 3,278,295 885,033 602,976 - 1,220,025 301,488 - 1,830,038

Total population in Tuscany at 31 december 2014: 3.7 millions inhabitants

Results 2) Estimation of the presumed ADR-related cost savings within a regional healthcare system

Conclusions •  Estimation of costs due to ADRs is a critical issue.

•  Studies evaluating ADR costs are very heterogeneous, owing to patients characteristics, clinical settings and class of drugs considered.

•  Our analysis showed that the mean cost of a serious ADR, in studies reporting costs in Euros, is about € 4,100, € 82 for a not-serious ADR, and that about 50% of ADRs are preventable.

•  The estimated costs in Tuscan Region in 2014 for total ADRs, ranged from 1.5 to 2 millions of euros/million-inhabitants.

•  Considering the estimated preventable ADRs in 2014, the Tuscan Regional Healthcare System could have avoided about 600,000 - 1,200,000 euros/million-inhabitants.

•  In the worst case scenario, Tuscan Regional Healthcare System could have saved yearly 300,000 euros/million-inhabitants.

•  Resource allocations to improve the regional pharmacovigilance systems might increase appropriateness and safety of therapies, thus reducing the costs incurred by regional healthcare systems to manage ADRs.

Acknowledgments

Prof. Blandizzi Corrado

Dr. Tuccori Marco

Convertino Irma

Mantarro Stefania

Marino Alessandra

Montagnani Sabrina

Saporiti Alessandra

Department of Clinical and Experimental Medicine, University of Pisa, Italy

Thank you for your kind attention