gms | German Medical Science

53. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e. V. (GMDS)

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie

15. bis 18.09.2008, Stuttgart

Systematic review of economic evaluations of cell-derived wound care products for the treatment of therapy-resistant chronic wounds

Meeting Abstract

Search Medline for

  • Astrid Langer - LMU München, München, Deutschland
  • Wolf Rogowski - Helmholtz Zentrum München, Neuherberg, Deutschland

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie. 53. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds). Stuttgart, 15.-19.09.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP-10

The electronic version of this article is the complete one and can be found online at:

Published: September 10, 2008

© 2008 Langer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background and Objective

Tissue engineering is an emerging field. The last ten years have seen new cell-derived treatment approaches for chronic wounds come to the market. Diabetic foot ulcers and venous leg ulcers are costly complications of their underlying diseases. Novel biotechnology products may reduce this burden for both the patient and the healthcare system in a cost-effective or even cost-saving way. To gain market access, manufacturers increasingly not only have to establish their products’ efficacy, yet also whether it provides cure at an accepted cost per health gain.

The objective of this systematic review was to assess the health economic evidence of these products. It was part of a study on the Regenerative Medicine in Germany, funded by the German Ministry of Education and Research. (A short version of the project report is available at:


Only full health economic evaluations of cell-derived wound care products for the treatment of therapy-resistant chronic wounds in English, French or German were considered for inclusion. Acellular artificial skin and skin substitutes indicated only for use in burns were excluded. Furthermore, economic evaluations included in an earlier systematic review [1] were excluded.

On the basis of an extensive explorative search, an appropriate algorithm for a systematic database search was developed. The following databases were searched to identify relevant literature: Cochrane Library, DARE, Embase, HTA Database, NHS EED and PubMed. Additionally, the internet was searched by Google Scholar, and references of recent economic evaluations and reviews were tracked. The search was updated until March 2008. The exploratory search generated a set of 11 economic evaluations of cell-derived products as defined for this review. Most studies were retrieved by using the following search algorithm: (“Biological Dressings”[Mesh] OR “Collagen”[Mesh] OR “Skin, Artificial”[Mesh] OR “Bandages”[Mesh] OR “Platelet-Derived Growth Factor”[Mesh]) AND (“Cost-Benefit Analysis”[Mesh] OR “economics”[Subheading]).

Two reviewers independently undertook assessment of study quality. Studies were assessed by an abbreviated synthesis of two recent quality checklists for health economic evaluations (available from the authors upon request) [2], [3]. Health economic evidence was considered good, if the health economic evaluations met the standard of transparency, if the underlying results were stable in the sensitivity analysis and if no unexplained inconsistencies between studies were observed.


Eleven health economic evaluations were included. Three biotechnology products were identified for which cell-derived wound care products for the treatment of chronic leg ulcers were economically assessed. All products are already available on the market: (1) Apligraf®, a bilayered living human skin equivalent indicated for the treatment of diabetic foot ulcers and venous leg ulcers (five studies). (2) Dermagraft®, a human fibroblast-derived dermal substitute. It is indicated only for use in the treatment of full-thickness diabetic foot ulcers greater than 6 weeks duration, which extend through the dermis, but without tendon, muscle, joint capsule, or bone exposure (one study). (3) Regranex® Gel, a human platelet-derived growth factor for the treatment of deep neuropathic diabetic foot ulcers (five studies).

None of the identified products met all criteria of good economic evidence. Health economic evidence is therefore limited. The studies considered in this review were of varying methodological quality. However it is becoming increasingly evident that some of these products have cost-benefit advantage despite their high initial cost. Results range from cost-effective to cost-saving. Incremental costs per ulcer month averted with Regranex® Gel over good wound care alone ranged from $US19 [4] to cost-saving. The results of most studies were sensitive to initial costs of the products and efficacy rate.


Treating chronic leg ulceration with novel biotechnology products may be less expensive than treating them with standard treatment alone, because a greater fraction of ulcers heal, and those that do so have a reduced time to heal coupled with a reduced risk of amputation, thus reducing the number of patient-months that require costly treatment. The following factors limit the validity of the evaluation results in German clinical practice:

  • Most studies are based on RCTs that typically have higher healing rates than seen in routine clinical practice.
  • The economic evaluations were heterogeneous in target populations, ulcer grades, prevalence of pertinent co-morbidities, resource use, etc.
  • Reimbursement systems, relative prices, and treatment patterns may have important impacts on resource usage and costs, thus international study results could be applied to the German healthcare system only by relating them to German-specific protocols of care.

Despite the limitations of the studies of which many were manufacturer-sponsored, it is evident that defining wound care costs exclusively as cost of biotechnology products used is not appropriate. In addition to the limited health economic evidence, the clinical benefits of these novel biotechnology products also deserve study to enhance cost-effectiveness information for informed treatment decisions.


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