The economic value of reducing medication dosing frequency with drug delivery technologies: an evidence assessment

Figures & data

Figure 1. Flow diagram of literature search strategy.

Table 1.  QHES grading system for cost-effectiveness studies (Chiou et al., 2003)^[7].

Was the study objective presented in a clear, specific, and measurable manner?

Were the perspective of the analysis and reasons for its selection stated?

Were variable estimates used in the analysis from the best available source (i.e., RCT – best, expert opinion – worst)?

If estimates came from a subgroup analysis, were the groups pre-specified at the beginning of the study?

Was uncertainty handled by: (1) statistical analysis to address random events; (2) sensitivity analysis to cover a range of assumptions?

Was incremental analysis performed between alternatives for resources and costs?

Was the methodology for data abstraction (including value health states and other benefits) stated?

Did the analytic horizon allow time for all relevant and important outcomes? Were benefits and costs that went beyond 1 year discounted (3–5%) and justification given for the discount rate?

Was the measurement of costs appropriate and the methodology for the estimation of quantities and unit costs clearly described?

Were the primary outcome measure(s) for the economic evaluation clearly stated and were the major short term, long term, and negative outcomes included?

Were the health outcomes measures/scales valid and reliable? If previously tested valid and reliable measures were not available, was justification given for the measures/scales used?

Were the economic model (including structure), study methods and analysis, and the components of the numerator and denominator displayed in a clear transparent manner?

Were the choice of economic model, main assumptions and limitations of the study stated and justified?

Did the author(s) explicitly discuss direction and magnitude of potential biases?

Were the conclusions/recommendations of the study justified and based on the study results?

Was there a statement disclosing the source of funding for the study?

Table 2.  Description of cost-effectiveness studies included in the review.

Authors, year of publication	Chronic disease or condition	Pharmaceutical interventions (mode of administration)	Dosing frequency*
Guest JF, Abegunde D, Ruiz FJ, 2004^[21]	Overactive bladder/urge incontinence	ER oxybutynin vs. IR oxybutynin (oral)	ER oxybutynin-once daily, IR oxybutynin twice to three times daily
Siebert U, Sroczynski G, Rossol S et al.s, 2003^[22]	Chronic hepatitis C	PegIFNα-2b + Ribavirin vs. nonpegylated IFNα-2b + Ribavirin (parenteral)	PegIFN-once weekly for 48 weeks, IFN-three times/week for 48–52 weeks
Buti M, Medina M, Casado MA et al., 2003^[23]	Chronic hepatitis C	PegIFNα-2b + ribavirin vs. nonpegylated IFNα-2b + ribavirin (parenteral)	PegIFN-once weekly for 48 weeks, IFN-three times/week for 48–52 weeks
Simon K, Gladysz A, Rotter K et al., 2006^[24]	Chronic hepatitis C	PegIFNα-2b + ribavirin vs. nonpegylated IFNα-2b + ribavirin (parenteral)	PegIFN-once weekly, IFN-three times/week for 24–48 weeks
Faber A, van Agthoven M, Kalverdijk LJ et al., 2008^[25]	Attention-deficit hyperactivity disorder (ADHD)	LA methylphenidate and IR methylphenidate (oral)	LA methylphenidate-once daily, IR methylphenidate- three times daily
Edwards NC, Locklear JC, Rupnow MFT et al., 2005^[26]	Schizophrenia	LAI risperidone (parenteral) and IR risperidone (oral)	LAI risperidone-once every two weeks, IR risperidone- once or twice daily

*If dosing frequency was not described in the published study, the information presented is the manufacturer recommended dosage administration from the drug product package insert.

ER = extended-release; IR = immediate-release; PegIFN = pegylated interferon; IFN = interferon; LA = long-acting; LAI = long-acting injection

Table 3.  Summary of methods and base-case results of studies included in the review.

First author	Study perspective	Methods	Data sources	Primary outcome measures	Base-case results
Guest JF^[21]	Payer perspective: United Kingdom (UK) - National Health Service, France - Social Security, Austria - Sick Funds	Decision-analytic models	Clinical estimates were obtained from the published literature and expert opinion. Resource utilization estimates were obtained from panel of clinicians	Expected reduction in the number of daily incontinence episodes and expected reduction in the number of daily micturitions at 6 months following the start of treatment	UK: ER oxybutynin was dominant France: ER oxybutynin was cost effective: €64/additional reduction in number of daily incontinence episode, €39/additional reduction in number of daily micturitions Austria: ER oxybutynin was dominant
Siebert U^[22]	German societal	Decision-analytic model	Clinical estimates were obtained from an international randomized clinical trial. Outcome estimates were obtained from a cross sectional interview-based quality-of-life study at a German health center. Cost estimates were obtained from patient data in the German healthcare system	QALY	PegIFN + R (fixed dose): €11,800/QALY, PegIFN + R (weight-based): €6,600/QALY
Buti M^[23]	Spanish healthcare system	Decision-analytic model	Clinical estimates and outcome estimates were obtained from the published literature. Cost estimates were obtained from databases in the Spanish healthcare system	QALY	PegIFN + R (fixed dose): €3,737/QALY, PegIFN + R (weight-based): €721/QALY
Simon K^[24]	Polish National Health Service (National Health Fund)	Decision-analytic model	Clinical estimates were obtained from clinical trial results and the published literature. Cost data were obtained from healthcare databases in the Polish healthcare system	LYG	PegIFN + R (fixed dose) all genotypes: 23,844 PLN/1 LYG PegIFN + R (weight-based) all genotypes: 9,124 PLN/1 LYG
Faber A^[25]	The Netherlands societal	Decision-analytic model	Clinical and resource use estimates were obtained from the published literature and from expert opinion. Outcome estimates were derived from a utility study conducted in the UK	QALY	LA methylphenidate: €2,004/QALY
Edwards NC^[26]	U.S. Healthcare payers	Decision-analytic model	Model estimates were obtained from the published literature, unpublished data from clinical trials, and the Consumer Health Sciences database. Expert opinion was also used as a secondary data source	Number of relapse days per year and total direct medical costs per patient per year	LAI risperidone was dominant

ER, extended-release; QALY, quality-adjusted life year; PegIFN, pegylated interferon; LYG, life years gained; €, Euro; PLN, Polish zloty; LA, long-acting; LAI, long-acting injection.

Table 4.  Results of quality assessment using QHES grading system^[6].

Criteria (weighted score)	Guest JF^[21]	Siebert U^[22]	Buti M^[23]	Simon K^[24]	Faber A^[25]	Edwards NC^[26]	Mean	Median	Standard deviation
1. Objective (7)	7	7	7	7	7	7	7	7	0
2. Perspective (4)	0	4	4	4	4	4	3.3	4	1.6
3. Data source (8)	0	8	8	8	0	8	5.3	8	4.1
4. Subgroup analysis (1)	NA 1 (0)	1	NA 1 (0)	1	1	NA 1 (0)	1 (0.5)	1 (0.5)	0 (0.5)
5. Uncertainty evaluation (9)	9	9	9	0	9	9	7.5	9	3.7
6. Incremental analysis (6)	6	6	6	6	6	6	6	6	0
7. Data abstraction (5)	5	5	5	5	5	5	5	5	0
8. Time horizon/discounting (7)	7	7	7	7	7	7	7	7	0
9. Costs (8)	0	8	8	8	0	8	5.3	8	4.1
10. Outcomes (6)	6	6	6	6	6	6	6	6	0
11. Instruments (7)	NA 7 (0)	7	7	7	7	NA 7 (0)	7 (4.7)	7 (7)	0 (3.6)
12. Presentation (8)	8	0	0	0	8	0	2.7	0	4.1
13. Rationale and justification (7)	7	7	7	0	7	0	4.7	7	3.6
14. Biases (6)	0	6	0	0	0	0	1	0	2.4
15. Conclusions (8)	8	0	8	8	8	8	6.7	8	3.3
16. Funding disclosure (3)	3	3	0	3	3	3	2.5	3	1.2
Total score	74 (66)	84	83 (82)	70	78	79 (71)	78 (75.2)	78.5 (74.5)	5.3 (7.2)

NA, Not applicable.

Scores in () = Scores calculated using conservative scoring method where any criterion not applicable to the study was assigned zero points as opposed to maximum points.

Chiou CF, Hay JW, Wallace JF, et al. Development and validation of a grading system for the quality of cost-effectiveness studies. Med Care 2003; 41: 32–44

 PubMed Web of Science ®Google Scholar

Guest JF, Abegunde D, Ruiz FJ. Cost effectiveness of controlled-release oxybutynin compared with immediate-release oxybutynin and tolterodine in the treatment of overactive bladder in the UK, France and Austria. Clin Drug Invest 2004; 24: 305–321

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Siebert U, Sroczynski G, Rossol S, et al. Cost effectiveness of peginterferon α–2b plus ribavirin versus interferon α–2b plus ribavirin for initial treatment of chronic hepatitis C. Gut 2003; 52: 425–432

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Buti M, Medina M, Casado MA, et al. A cost-effectiveness analysis of peginterferon alfa–2b plus ribavirin for the treatment of naïve patients with chronic hepatitis C. Aliment Pharmacol Ther 2003; 17: 687–694

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Simon K, Gladysz A, Rotter K, et al. Cost effectiveness of replacing recombinated interferon α–2b with its pegylated form in combination with ribavirin for the therapy of chronic HCV infection in Poland. Adv Clin Exp Med 2006; 15: 453–462

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Faber A, van Agthoven M, Kalverdijk LJ, et al. Long-acting methylphenidate – OROS in youths with attention-deficit hyperactivity disorder suboptimally controlled with immediate-release methylphenidate: a study of cost effectiveness in The Netherlands. CNS Drugs 2008; 22: 157–170

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Edwards NC, Locklear JC, Rupnow MFT, et al. Cost effectiveness of long-acting risperidone injection versus alternative antipsychotic agents in patients with schizophrenia in the USA. Pharmacoeconomics 2005; 23(Suppl 1)75–89

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Gold MR, Siegel JE, Russell LB, et al. Cost-effectiveness in Health and Medicine. Oxford University Press, New York 1996

 Google Scholar