Proposal for a new classification of orphan and/or rare conditions based on clinical characteristics that determine the applicability of different research methods to their study.

• Autores: Mònica Gómez Valent
• Directores de la Tesis: Caridad Pontes García (dir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2017
• Idioma: español
• Tribunal Calificador de la Tesis: Fernando De Andrés Rodriguez Trelles (presid.), Maria Queralt Gorgas Torner (secret.), Inmaculada Danés (voc.)
• Programa de doctorado: Programa de Doctorado en Farmacología por la Universidad Autónoma de Barcelona
• Materias:
  • Ciencias médicas
    • Farmacología
      • Evaluación de medicamentos
• Enlaces
  • Tesis en acceso abierto en:  DDD  TDX 
• Resumen

  • Background: Rare diseases are those that affect a small number of people and have a particularly low prevalence compared to the general population. While individually these entities are uncommon, as a group they are an important cause of chronic illness, disability and premature death in both children and adults. The European Union considers diseases to be rare when they affect not more than 5 in 10000 individuals. Methodologies aimed to increase efficiency of clinical studies in small populations have been only scarcely applied to the clinical development of new orphan medicinal products (OMP). The lack of references and guidance may explain reluctance to alternative methodologies, but specific guidance is impractical due to the huge number of existing orphan conditions. A systematic approach to grouping medical conditions based on their methodological requirements may be useful to allow generalisation of recommendations to type conditions, rather than to single disease models.

    Hypothesis: Orphan conditions can be grouped through a systematic approach based on their methodological requirements, and the resulting clustering can be an effective tool for establishing specific recommendations for the study of groups of conditions rather than for individual conditions, that would facilitate a more structured approach to regulatory development and decision making.

    Objective: To propose a clustering of medical conditions based on their methodological requirements, with the aim to provide a framework for guidance on treatment development and regulatory decision making on OMP.

    Methods: The characteristics of medical conditions which may be relevant to study design and regulatory decision making have been identified, and a number of sample conditions have been described in detail for these characteristics and used to produce a database that has been analysed through Multiple Correspondence Analysis (MCA) to identify clusters of conditions. These have been refined and validated from a clinical and regulatory perspective which included a meeting with clinical specialists with recognised expertise in the field of orphan diseases, in order to know their opinion towards the proposed classification and to get insights on potential weaknesses of the approach.

    Results: Six groups of medical conditions are proposed which share applicability of similar methodologies to their study: single acute episode, repeated acute episodes, slow/non progressive, progressive led by one organ or system, progressive multidimensional multi-organ and staged condition. A total of 125 medical indications with positive opinions issued by the EMA on OMP applications have been clustered to test applicability of inferences.

    The methodological inferences to the different established clusters implied a first step of listing the variables that had a high discriminative value for each cluster, and a second step to make detailed descriptions of these determinants in relation to aspects required to define clinical study designs. This was done in order to test the validity of the proposed clusters to their main purpose as issuing common recommendations on product development for a given group of conditions.

    The results of the surveys given to members of the clinical board were collected and summarised. Clinicians agreed on the fact that current methods in clinical research have room for a more structured approach and that would help to the access to new treatments urgently needed, and considered it would be useful to guide methodological decision for industry and regulators, also to investigators and health technology assessment.

    Conclusions: A new clustering of conditions based on their methodological requirements is proposed as a framework for guidance on treatment development and regulatory decision making on OMP.