An update on the first decade of the European centralized procedure: how many innovative drugs?

Abstract

Aims: In a previous paper, we proposed an algorithm to assess the degree of therapeutic innovation of the agents approved by the European centralized procedure, which must be followed by biotechnological products and is optional for drugs claimed as innovative. A low overall degree of therapeutic innovation (about 30%) was found. This figure may be an underestimate of the actual level of innovation, because common biotechnological products, such as recombinant human insulins, must follow this procedure. To test the hypothesis that therapeutic innovation prevails among nonbiotechnological products, we evaluated separately the degree of therapeutic innovation of biotechnological vs. nonbiotechnological agents in the first decade of European Medicines Agency activity, also studying a possible time trend.

Methods: We assessed, for each drug: (i) the seriousness of the target disease, (ii) the availability of previous treatments, and (iii) the extent of therapeutic effect according to the previously proposed algorithm.

Results: Our analysis considered 251 medicinal products corresponding to 198 active substances, classified according to four main areas as therapeutic agents (88.9%), diagnostics (5.5%), vaccines (5.1%) and life-style drugs (0.5%). Among all therapeutic agents, 49 out of 176 agents (28%) were classified as having an important degree of therapeutic innovation. Fifteen out of 60 biotechnological therapeutic agents were considered important therapeutic innovations (25%), whereas this figure was 29% for nonbiotechnological agents.

Conclusions: Among active substances claimed as innovative by the manufacturers, only a minority deserve this definition according to our algorithm.

Figure 1

Algorithm used to assign the overall score for innovation. Disease seriousness: a, drugs for serious diseases; b, drugs for risk factors for serious diseases; c, drugs for nonserious diseases. Availability of treatments: a, drugs for diseases without recognized standard treatment; b, drugs for diseases where subsets of patients are less responsive to marketed drugs and/or other medical interventions; c, drugs for diseases responsive to marketed drugs or other medical interventions (c₁, more effective or safer or with a better kinetics than existing drugs; c₂, mere pharmacological innovation, i.e. drugs with a new mechanism of action; c₃, mere technological innovation, i.e. a new chemical or biotechnological product with a therapeutic role similar to already existing ones). Therapeutic effect: a, major benefit on clinical end-points (e.g. increased survival rate and/or quality of life) or validated surrogate end-points; b, partial benefit on the disease (on clinical or validated surrogate end-points) or limited evidence of a major benefit (inconsistent results); c, minor or temporary benefit on some aspects of the disease (e.g. only partial symptomatic relief of a serious disease)

Figure 2

Distribution of the European Medicines Agency approved products according to the Anatomic Therapeutic Chemical classification I level and biotechnological source. Biotechnological (), nonbiotechnological ()

Figure 3

Time trend of the degree of therapeutic innovation among therapeutic agents in the period 1995–2004. Important (), moderate (), modest (), pharmacological (), tecnological (▪)