. 2016 Aug 24;8:413–426. doi: 10.2147/CEOR.S115689

Table 1.

Main characteristics of the included studies

Study	Design	Country	Study period	Setting	Characteristics of the patients	Suspected drug(s)	Type of ADE	Type and structure of costs	Risk of bias
Pirmohamed et al (2004)¹⁸	Prospective cohort study	England	6 months	Outpatient	Patients aged >16 years admitted to hospital	Any drug	Any ADE	Costs: total time spent in hospital, and invasive investigations performed	Moderate
Bordet et al (2001)¹⁹	Prospective cohort study	France	18 months	Outpatient	Patients admitted to a cardiological hospital	Any drug	Any ADE	Direct costs: A) additional investigations, B) laboratory tests, C) noninvasive procedures, D) invasive monitoring or procedures, E) additional treatment, and F) increased length of stay	Low
Carrasco-Garrido et al (2010)²⁰	Retrospective cohort study	Spain	6 years	Outpatient	Patients admitted to hospital	Any drug	Any ADE	Direct medical costs	Low
Kim et al (2009)²¹	Retrospective cohort study	US	5 years	Outpatient	Patients treated for atrial fibrillation	Rhythm-control, rate-control, and combined rhythm/rate-control	Any ADE	Direct medical costs: inpatient (facility and professional) and outpatient (medical, laboratory, and pharmacy)	Low
Yee et al (2005)²²	Retrospective cohort study	US	1 year	Outpatient	Patients aged >18 years who visited the ED	Any drug	Any ADE	Costs: drugs administered, laboratory tests, and follow-up outpatient clinic visits	Moderate
Lagnaoui et al (2000)²³	Retrospective cohort study	France	4 months	Outpatient	Patients admitted to hospital	Any drug	Any ADE	Costs: length of stay and hospitalization costs	Moderate
Leendertse et al (2011)¹³	Prospective case–control study	The Netherlands	53 days	Outpatient	Patients aged >18 years admitted to hospital	Any drug	Preventable ADE-induced hospitalization	Medical costs during hospital admission; production loss costs: time off work and reduced productivity on the job	Moderate
Hafner et al (2002)²⁴	Retrospective case–control study	US	3 months	Outpatient	Patients who visited the ED	Any drug	Any ADE	Costs: hospitalized days and hospitalized charges	Low
Bates et al (1997)²⁵	Prospective case–control study	US	6 months	Outpatient	Patients admitted to hospital	Any drug	Any ADE	Costs: intensive care unit, intermediate and routine care, pharmacy, laboratory, and surgery	Low
Rottenkolber et al (2011)²⁶	PV database^*	Germany	2 years	Outpatient	Patients admitted to hospital	Any drug	Spontaneously reported ADE leading to hospitalization	Direct costs: A) hospitalizations; B) medical consultations; C) laboratory tests; and D) drug treatments	–
Senst et al (2001)²⁷	Prospective case–control study	US	53 days	Inpatient and outpatient	Patients having ADE during hospitalization and patients admitted to hospital due to ADE	Any drug	Any ADE	Costs of resource use	Low
Tafreshi et al (1999)²⁸	Prospective cohort study	US	2 months	Outpatient	Patients admitted to hospital	Any drug	Any ADE	Costs: total cost to the institution, not charges to the patient, or third-party payers, including overhead costs such as personnel and supplies	Low
Schneeweiss et al (2002)²⁹	Prospective cohort study	Germany	2 years and 6 months	Outpatient	Patients admitted to hospital	Any drug	Any ADE, except skin ADE	Costs: reimbursement per hospital day	Low
Du et al (2013)¹⁴	Prospective cohort study	US	7 months	Outpatient	Children (median age 4 years) admitted to ICU	Any drug	Any ADE	Costs: facility-based cost data	Low
Rottenkolber et al (2012)³⁰	Retrospective cohort study with a case–control analysis	Germany	1 year	Inpatient and outpatient	Patients admitted to hospital	Any drug	Any ADE	Direct medical costs: personnel costs (clinicians, nursing staff, and medical technicians) and nonpersonnel costs (pharmaceuticals, implants, grafts, and medical expenditure not otherwise specified); medical and nonmedical infrastructures (general ward, intensive care units, operating room, anesthesia, cardiac and endoscopic diagnoses and therapies, radiology, laboratory tests, etc)	Low
Hug et al (2012)³¹	Retrospective cohort study	US	20 months	Inpatient	Patients aged >18 years being treated in hospital	Any drug	Any ADE	Diagnosis-related group weighted hospitalization cost and cost of length of stay	Low
Schneider et al (1995)³²	Retrospective cohort study	US	2 years	Inpatient	Patients having an MRP during hospitalization	Any drug	Any ADE	Direct costs: A) extra laboratory tests, B) noninvasive procedures, C) additional treatments, D) invasive monitoring or procedures, E) increased length of stay, and F) intensive care	Moderate
Suh et al (2000)³³	Prospective case–control study	US	5 months	Inpatient	Patients having ADE during hospitalization	Any drug	Any ADE	Costs: length of stay and hospitalization costs	Low
Classen et al (1997)³⁴	Retrospective case–control study	US	4 years	Inpatient	Patients admitted to hospital	Any drug	Any ADE	Cost of hospitalization	Low
Giuliani and Marzola (2013)³⁵	Retrospective cohort study	Italy	5 years	Inpatient	Patients with NSCLC	Erlotinib	Skin toxicity	Direct medical costs: based on mean duration of skin rash and range of costs related to different drug prices	Low
Gyllensten et al (2014)³⁶	Retrospective cohort study	Sweden	3 months	Inpatient and outpatient	Patients aged >18 years with health care encounters	Any drug	Any ADE	Costs: hospitalized days and hospitalized charges	Low
Lang et al (2009)⁴⁸	Retrospective cohort study	US	6 years	Inpatient and outpatient	Patients aged >35 years with advanced squamous cell carcinoma of the head and neck	Radiotherapy, chemoradiotherapy	Any ADE	Costs: A) hospital inpatient, B) hospital outpatient, C) physician, and D) outpatient pharmacy	Low
Paessens et al (2011)⁴⁹	Prospective cohort study	Germany	2 years and 6 months	Inpatient and outpatient	Patients undergoing multidrug chemotherapy with NSCLC and lymphoproliferative disorder	Multidrug chemotherapy	Any ADE	Costs: cost of hospitalization, cost of drugs, medical treatment, and diagnostic procedures	Moderate
Ray et al (2013)⁵⁰	Retrospective cohort study	US	10 years and 7 months	Inpatient and outpatient	Patients with CRC, NSCLC, or HNC	EGFRI	Dermatologic ADE	Costs: pharmacy (EGFRI drug costs, other pharmacy costs), medical services (admissions, ED visits, outpatient visits, other medical services, ie, laboratory, radiology), and total costs (pharmacy and medical costs)	Low
Borovicka et al (2011)³⁷	Retrospective cohort study	US	2 years and 8 months	Inpatient and outpatient	Patients diagnosed with cancer receiving one molecularly targeted agent	Molecularly targeted cancer agents	Dermatologic ADE	Costs for medications, clinic visits, laboratory and diagnostic testing, and therapeutic procedures	Low
Noize et al (2010)³⁸	PV database^*	France	18 years	Inpatient and outpatient	Any	Ketoprofen for topical use	Spontaneously reported cutaneous ADE	Direct costs: A) hospitalizations, B) medical consultations, C) laboratory tests, and D) drug treatments	–
Suh et al (2012)³⁹	Retrospective cohort study	US	5 years	Inpatient and outpatient	Patients aged >18 years with PD	Levodopa	Dyskinesia	Medical costs: hospitalizations, outpatient services, and ED; Medication costs: dispensed by outpatient, community-based, or mail-service pharmacies	Low
Foley et al (2010)⁴⁴	Retrospective cohort study	US	3 years	Inpatient and outpatient	Patients with CRC	Cetuximab	Infusion ADE	Costs: A) inpatient care, B) inpatient length of stay, C) ED, D) outpatient care, and E) prescription	Low
Parekh et al (2014)¹⁵	Retrospective cohort study	US	4 years	Inpatient and outpatient	Patients aged >65 years with diabetes and a concomitant infection	Antimicrobial drugs	Hypoglycemia	Costs: emergency department services, hospitalizations, and professional services	Low
Wan et al (2015)¹⁶	Retrospective cohort study	US	1 year	Inpatient and outpatient	Patients aged >18 years	Opioids	Constipation	Costs: costs for inpatient, pharmacy, outpatient, emergency department, long-term care facility, and other costs	Low
Tundia et al (2011)¹⁷	Retrospective case–control study	US	1 year	Inpatient and outpatient	Children and adolescents aged ≤20 years having ADE during hospitalization and patients admitted to hospital due to ADE	Any drug	Pediatric ADE	Hospital costs, length of stay	Low

Notes:

Methodological quality was not assessed for pharmacovigilance databases studies.

Abbreviations: ADE, adverse drug event; CRC, colorectal cancer; ED, emergency department; EGFRI, epidermal growth factor receptor inhibitor; HNC, head and neck cancer; ICU, Intensive care unit; MRP, medication-related problems; NSCLC, non-small-cell lung cancer; PD, Parkinson disease; PV, pharmacovigilance.