Cost Estimations of Managing Adverse Drug Reactions in Hospitalized Patients: A Systematic Review of Study Methods and Their Influences
Abstract
:1. Introduction
2. Results
2.1. Characteristics of the Included Studies
2.2. ADR Identification Methods, Incidence, and Length of Stay (LOS)
2.3. Study Quality and Risk of Bias
2.4. Method of Cost Calculation
2.5. Cost of ADR
3. Discussion
Streamlining ADR Costing Methods
4. Methods
4.1. Search Strategy
4.2. Study Selection Criteria
4.3. Data Extraction
4.4. Quality Assessments
4.5. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author (Publication Date) | Suh et al. (2000) [38] | Bordet et al. (2001) [10] | Wasserfallen et al. (2001) [33] | Wu and Pantaleo (2003) [37] | Yee et al. (2005) [34] | Patel et al. (2007) [31] | Chan et al. (2008) [39] | Pattanaik et al. (2009) [32] | Carrasco-Garrido et al. (2010) [35] | Rottenkolber et al. (2011) [36] | Rajakannan et al. (2012) [40] | Geer et al. (2016) [30] |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Country | USA | France | Switzerland | USA | USA | India | Taiwan | India | Spain | Germany | India | India |
Type of study design | Prospective | Prospective | Prospective | Retro-spective | Retro-spective | Prospective | Prospective | Prospective | Retro-spective | Retro-spective | Prospective | Prospective |
Single/Multi centre | Single centre | Single centre | Single centre | Single centre | Single centre | Single centre | Single centre | Single centre | Multicentre | Multicentre | Single centre | Single centre |
Study duration (months) | 5 | 18 | 5 | 24 | 3 | 1.5 | 36 | 4 | 72 | 24 | 6 | 9 |
No. Patients included | 9311 | 16,916 | 3195 | 191 | 2225 | 2046 | 142,295 | 1833 | 20,712,399 | 57,000 | 1438 | 5483 |
Age range | Mean 56.6 (SD 20.3) | Mean 66.0 (SD 2.0) | Mean 61.4 (Range 16–93) | Mean/median age (NR) | Mean 60.2 (SD 14.2) | Mean 40.0 (NR) | Mean 66.0 (SD 2.0) | Mean or median age (NR) | Mean or median age (NR) | Mean 71.0 (14.7) Median 74 (17–103) | Mean 45.9 (SD 15.8) | Mean 62.0 (SD 2.3) |
Gender | Male: 50.4% Female: 49.6% | Male: 55.3% Female: 44.7% | Male: 47.0% Female: 53.0% | Male: 44.0% Female: 56.0% | Male: 92.3% Female: 7.3% | NR | Male: 54.0% Female: 46.0% | Male: 57.7% Female: 42.3% | Male: 50.5% Female: 49.5% | Male: 41.8% Female: 58.2% | Male: 42.3% Female: 57.7% | Male: 38.6% Female: 61.4% |
Setting (medical specialty) | General medical | Medical, surgical, paediatrics, and ICU | Emergency | Emergency | Emergency | Emergency | General medical | Medical emergency | General hospital admission | Internal medicine | Medical wards | Internal medicine and emergency |
Author (Publication Date) | Suh et al. (2000) [38] | Bordet et al. (2001) [10] | Wasserfallen et al. (2001) [33] | Wu and Pantaleo (2003) [37] |
ADR definition and type classification | WHO | WHO | WHO | WHO |
Method of ADR detection (ADR defined by WHO) | Assessed by healthcare providers (pharmacists, nurses) from ADR reporting system and medical records. | Assessed by healthcare professionals (physicians and nurses) upon admission at all units and reviewing medical records. | Assessed by healthcare providers (research investigators) from hospital admission book. | Assessed by healthcare providers from ADR-related hospital admissions and patient’s medication profiles. |
Method of ADR severity | No reference Mild: 30.0% Moderate: 53.0% Severe: 17.0% | WHO Mild: 53% Moderate: 34% Severe: 10% | No reference Evaluated using 5-point scale | NR |
Causality assessment of ADR | Naranjo probability scale Definite: 8.0% Probable: 69.0% Possible: 21.0% Doubtful: 2.0% | French method Very likely: 1.0% Likely: 21.0% Possible: 25.0% Doubtful: 53.0% | WHO algorithm for imputability Certain: 18.0% Likely: 26.0% Possible: 56.0% | NR |
Admission due to ADR (%) | 2.1 | 2.2 | 7.1 | NR |
Preventable ADR (%) | NR | NR | 20.0 (10-item Qs, Livio 1998) | NR |
Length of hospitalization due to ADR (days) | 1–3 ADR: 10.3 (10.7) [mean] >4 ADR: 12.8 (6.8) [mean] | 11 (NR) [mean] | 9.0 (0.6) [mean] | 8.0 (3.0) [mean] 5.0 (NR) [median] (Range 0 to 99 days) |
Top five causative agents of ADR (therapeutic group) | Anti-infectives (17.1%) CVS drugs (16.5%) Antineoplastic (14.6%) NSAIDs (14.6%) Psychotropics (5.5%) | CVS Agents (36.0%) Contrast media (20.0%) Anti-infectives (14.0%) Anticoagulant (13.0%) Diuretics (6.0%) | Antineoplastic (22.7%) Anticoagulant (8.4%) NSAIDs (8.1%) Analgesics (8.1%) Antihypertensive (7.3%) | Antidiabetics (27.8%) CVS drugs (26.2%) Anticoagulant (15.2%) Psychotropics (11.5%) Analgesics (10.0%) |
Top five ADRs | Gastrointestinal (24.4%) Dermatology (18.6%) Immunology (14.5%) CNS (13.2%) Hematological (9.9%) | Cutaneous (24.0%) CVS condition (21.0%) Metabolic cond. (12.0%) Coagulation (10.0%) CNS (10.0%) | GI bleeding (22.2%) Febrile neutropenia (14.4%) Hypotension (7.9%) Enterocolitis (5.7%) Hypoglycemia (4.6%) | Endocrine (28.3%) CVS condition (24.1%) Hematological (15.2%) Neurologic (14.1%) Renal (14.1%) |
Author (Publication Date) | Yee et al. (2005) [34] | Patel et al. (2007) [31] | Chan et al. (2008) [39] | Pattanaik et al. (2009) [32] |
ADR definition and type classification | WHO | WHO | WHO | WHO |
Method of ADR detection (ADR defined by WHO) | Assessed by healthcare professionals upon admission at ED and reviewing electronic medical record system. | Assessed by healthcare professionals (senior lecturers and authors) upon admission at ED. | Assessed by healthcare providers from hospital admission cases. | Assessed by healthcare professionals (doctors, pharmacists, nurses) upon admission at medical ED. |
Method of ADR severity | NR | Modified Hartwig and Siegel Scale. Mild: 18.5% Moderate: 74.7% Severe: 6.8% | WHO Mild: 34.4% Moderate: 58.5% Severe: 7.1% | NR |
Causality assessment of ADR | Naranjo probability scale Definite:1.0% Probable: 31.0% Possible: 68.0% | Naranjo probability scale Definite:3.8% Probable: 85.9% Possible: 10.3% | Naranjo probability scale Definite: 4.1% Probable: 73.2% Possible: 22.3% Doubtful: 0.4% | Naranjo probability scale Definite: 86.0% Probable: 6.0% Possible: 8.0% |
Admission due to ADR (%) | 1.1 | 6.9 | 0.03 | 1.4 |
Preventability of ADR (%) | NR | 59.6 (Hallas 1990) | NR | NR |
Length of hospitalization due to ADR (days) | 6.3 (NR) [mean] | 5 (NR) [median] (95% CI 5.37 to 7.11) | NR | 3 (NR) [median] |
Top five drugs causing ADR (therapeutic group) | Anticoagulant (22.1%) Anti-infectives (13.2%) Antineoplastic (13.2%) Antidiabetics (10.3%) Diuretics (8.8%) | Anti-TB agents (19.6%) Antiepileptic (13.6% Antimalarials (11.3%) Anticoagulants (9.4%) OHA (6.0%) | Anti-infectives (38.8%) Analgesics (11.0%) CVS drugs (9.9%) NSAIDs (5.7%) Antiepileptic (5.1%) | NR |
Top five nature of ADR occurred | Dermatologic allergic reaction (75.6%) | Hepatitis (10.6%) GI bleeding (9.1%) Gastritis (8.3%) | Cutaneous (52.5%) Hematological (10.8%) CVS condition (9.6%) Hepatic (5.9%) GI effects (5.0%) | NR |
Author (Publication Date) | Carrasco-Garrido et al. (2010) [35] | Rottenkolber et al. (2011) [36] | Rajakannan et al. (2012) [40] | Geer et al. (2016) [30] |
ADR definition and type classification | WHO | WHO Edwards and Aronson (2000) classification | WHO | WHO Rawlins and Thomson classification |
Method of ADR detection (ADR defined by WHO) | Assessed by healthcare professionals (physicians) from hospital admission database. | Identified by evaluators from pharmacovigilance database and reviewing medical history. | Identified by investigator based on indicator list developed during manual screening of patients. | Assessed by healthcare professionals (multidisciplinary medical team) through hospital admission cases. |
Method of ADR severity | NR | Hartwig severity scale Hosp: 89.3% Intensive: 9.1% Harm: 0.7% Fatal: 0.9% | Hartwig severity scale Mild: 36.6% Moderate: 61.5% Severe: 1.9% | Modified Hartwig and Siegel Scale. Mild: 41.5% Moderate: 48.8% Severe: 9.7% |
Causality assessment of ADR | NR | Begaud et al. (1985) algorithm Predictable: 91.1% Unpredictable: 7.8% | Naranjo scale Definite: 1.0% Probable: 61.2% Possible: 37.8% | Naranjo scale Definite: 5.3% Probable: 78.6% Possible: 16.1% |
Admission due to ADR (%) | 1.69 (1.65, 1.73) | 3.25 | 17.11 | 1.24 |
Preventability of ADR (%) | NR | 20.1 (Schumock and Thornton 1992) | NR | 81.6 (Hallas 1990) |
Length of hospitalization due to ADR (days) | 8.0 (10) [median] | 9.3 (7.1) [mean] | 5.0 (Range 5–28) [median] | 7 (NR) [median] |
Top five drugs causing ADR (therapeutic group) | Antineoplastic (21.5%) Steroids (13.5%) Anticoagulant (7.5%) CVS drugs (7.0%) Anti-infectives (6.3%) | Anticoagulant (18.3%) Antidiabetics (15.9%) Diuretics (10.0%) | Anti-infectives (27.6%) | Anti-infectives (40.9%) Anti-TB agents (13.2%) Steroids (14.0%) Anticoagulant (8.8%) NSAIDs (7.9%) |
Top five nature of ADR occurred | Neutropenia (5.0%) Chronic bronchitis (4.9%) CVS condition (3.1%) Neoplastic (3.0%) Pneumonia (2.9%) | GI bleeding (16.5%) Hypoglycemic (13.3%) Bradycardia (5.5%) Colitis (3.9%) Gastric ulcer (3.8%) | GI effects (19.5%) CNS condition (18.6%) Dermatology (15.4%) Metabolic cond. (15.1%) Hepatic (12.0%) | GI effects (23.7%) Dermatology (12.6%) CNS condition (11.7%) Hematological (10.0%) Metabolic cond. (9.6%) |
Study | Author | Year Published | Quality Assessment (Risk of Bias) 1 | Baseline Clinical Data 2 | Resource Use 2 | Costs 2 |
---|---|---|---|---|---|---|
1 | Suh et al. | 2000 | High | 1++ | 1++ | 1++ |
2 | Bordet et al. | 2001 | High | 1++ | 1++ | 1++ |
3 | Wasserfallen et al. | 2001 | High | 1++ | 1+ | 1+ |
4 | Wu and Pantaleo | 2003 | Moderate | 1+ | 1++ | 1++ |
5 | Yee et al. | 2005 | Moderate | 1+ | 1++ | 1++ |
6 | Patel et al. | 2007 | Moderate | 1++ | 1++ | 1++ |
7 | Chan et al. | 2008 | High | 1++ | 1++ | 1++ |
8 | Pattanaik et al. | 2009 | Moderate | 1++ | 1++ | 1++ |
9 | Carrasco-Garrido et al. | 2010 | High | 1+ | 1++ | 1++ |
10 | Rottenkolber et al. | 2011 | High | 1+ | 1+ | 1+ |
11 | Rajakannan et al. | 2012 | High | 1++ | 1++ | 1++ |
12 | Geer et al. | 2016 | Moderate | 1++ | 1++ | 1++ |
Authors (Date Published) | Type of Study Design | No. of Pat. (Cost Analysis) | Data Extraction (Database Used) | Cost Analysis Perspective | Cost Calculation | LOS Definition | Sensitivity Analysis | Total Cost ADR (Duration) | Cost/Case (As Reported, Mean (SD)) | Cost/Case, USD (Adjusted 2016) |
---|---|---|---|---|---|---|---|---|---|---|
Micro-costing or unit cost (component of resource use estimated and unit cost derived) | ||||||||||
Wasserfallen et al. (2001) [33] | Prospective | 229 | Admission database and medical records | Provider (health sector) | Hospital marginal costs divided by no. of patients in ward and computed according to no. of stays | Number of days spent in different wards | Imputability and avoidability figures (10–100%) | NR | CHF 3586.00 (342.00) | 2908.77 |
Yee et al. (2005) [34] | Retrospective | 274 | Admission database (ED) and medical records (electronic) and VAD system | Provider (health sector) | Costs from activity-based costing system implemented | NA | NR | USD 333,433.00 (12 wk) | USD 3704.00 (NR) | 4463.59 |
Patel et al. (2007) [31] | Prospective | 141 | Hospital admissions reports and patients’ profiles | Provider (health sector) | Products of total admission days for all patients admitted with ADR | Number of days admitted to hospital due to ADR | NR | INR 1.12 million (6 wk) | INR 6197.00 (NR) | 581.74 |
Chan et al. (2008 [39]) | Prospective | 564 | ADR reporting system and patients’ profiles | Provider (health sector) | Hospital cost for services related to ADR treatment based on hospital’s claim data system | NA | NR | USD 150,027.14 (36 mo) | USD 3489.00 (NR) | 3896.97 |
Pattanaik et al. (2009) [32] | Prospective | 92 | Admissions reports (ED) and patients’ profiles | Provider and patients (health and societal) | Cost for healthcare (direct) and non-healthcare (indirect) in ADR treatment | NA | For variability in components of the indirect cost | EUR 5556.00 (4 mo) | EUR 214.00 (NR) | 346.25 |
Rajakannan et al. (2012) [40] | Prospective | 246 | Patients’ medical records in wards (patient notes) | Payer (health sector) | Hospital cost for services related to ADR treatment based on hosp patient admin system | Number of days in ward due to ADR | NR | USD 36,451.00 (6 mo) | USD 115.00 (NR) | 327.38 |
Geer et al. (2016) [30] | Prospective | 342 | Hospital admissions reports and patients’ profiles | Provider (health sector) | Products of total admission days for all patients admitted with ADR | Measured by excess days: difference duration of hosp stays of ADR patient and mean duration of hosp stays for non-ADR patients | NR | USD 22,469.00 (9 mo) | USD 65.00 (NR) | 65 |
Case-mix group costing (gives cost by case or patient category, e.g., DRG) | ||||||||||
Suh et al. (2000) [38] | Prospective | 131 | Institutional database | Provider and payer (health sector) | DRG-based estimates (using hospital-specific cost/charge ratio) | NA | NR | USD 22,775 (SD 21,088.00) (5 mo) | USD 20,745.00 (20,040.00) (1–3 ADR) USD 34,445.00 (24,025.00) (>4 ADR) (Values were based on ADR cost per patient) | 28,082.65 (1–3 ADR) 46,628.44 (>4 ADR) (Values were based on ADR cost per patient) |
Carrasco-Garrido et al. (2010) [35] | Retrospective | 350,835 | Admission database (minimum basic data set, MBDS) and patients’ profiles | Payer (health sector) | DRG-based estimates (reimbursement) | NA | NR | EUR 272 million (12 mo) | EUR 4382.00 (NR) | 6668.84 |
Rottenkolber et al. (2011) [36] | Retrospective | 1834 | Regional regulatory database and admissions reports | Payer (health sector) | DRG-based estimates (reimbursement) | NA | NR | EUR 434 million (12 mo) | EUR 2250.00 (1321.00) | 3102.71 |
Average per diem (or daily cost) | ||||||||||
Bordet et al. (2001) [10] | Prospective | 371 | Admission database and medical records | Provider (health sector) | Hospital charges converted using hospital-specific cost/charge ratio | NA | NR | EUR 1815 million (18 mo) | EUR 4150.00 (NR) | 6222.52 |
Wu and Pantaleo (2003) [37] | Retrospective | 191 | Pharmacy depart. reports and medication profiles | Provider (health sector) | Hospital charges converted using hospital-specific cost/charge ratio | NA | NR | NR | USD 9491.00 (12,843.00) | 12,129.90 |
Concept | Examples of Similar Phrases |
---|---|
Population | “adult”, “children”, or “pediatric” |
ADR | “adverse drug reactions”, “drug toxicity”, “hospitalized adverse drug reactions”, “hospitalized side effect”, “hospitalized adverse effect”, “hospital acquired ADRs (MeSH)”, “hospital induced ADRs (MeSH)”, “ADRs occurred during hospitalization (MeSH)” |
Surveillance | “drug monitoring (MeSH)”, “drug surveillance program”, “pharmacovigilance” |
Cost | “ADR economic burden”, “direct cost”, “cost of illness”, “cost”, and “economic” |
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Abu, S.F.; Shafie, A.A.; Chandriah, H. Cost Estimations of Managing Adverse Drug Reactions in Hospitalized Patients: A Systematic Review of Study Methods and Their Influences. Pharmacoepidemiology 2023, 2, 120-139. https://doi.org/10.3390/pharma2020012
Abu SF, Shafie AA, Chandriah H. Cost Estimations of Managing Adverse Drug Reactions in Hospitalized Patients: A Systematic Review of Study Methods and Their Influences. Pharmacoepidemiology. 2023; 2(2):120-139. https://doi.org/10.3390/pharma2020012
Chicago/Turabian StyleAbu, Siti Fauziah, Asrul Akmal Shafie, and Haarathi Chandriah. 2023. "Cost Estimations of Managing Adverse Drug Reactions in Hospitalized Patients: A Systematic Review of Study Methods and Their Influences" Pharmacoepidemiology 2, no. 2: 120-139. https://doi.org/10.3390/pharma2020012
APA StyleAbu, S. F., Shafie, A. A., & Chandriah, H. (2023). Cost Estimations of Managing Adverse Drug Reactions in Hospitalized Patients: A Systematic Review of Study Methods and Their Influences. Pharmacoepidemiology, 2(2), 120-139. https://doi.org/10.3390/pharma2020012