EPMA Journal

, Volume 10, Issue 3, pp 195–209 | Cite as

Inappropriate modeling of chronic and complex disorders: How to reconsider the approach in the context of predictive, preventive and personalized medicine, and translational medicine

  • Soroush SeifiradEmail author
  • Vahid Haghpanah


Preclinical investigations such as animal modeling make the basis of clinical investigations and subsequently patient care. Predictive, preventive, and personalized medicine (PPPM) not only highlights a patient-tailored approach by choosing the right medication, the right dose at the right time point but it as well essentially requires early identification, by the means of complex and state-of-the-art technologies of unmanifested pathological processes in an individual, in order to deliver targeted prevention early enough to reverse manifestation of a pathology. Such an approach can be achieved by taking into account clinical, pathological, environmental, and psychosocial characteristics of the patients or an individual who has a suboptimal health condition. Inappropriate modeling of chronic and complex disorders, in this context, may diminish the predictive potential and slow down the development of PPPM and consequently modern healthcare. Therefore, it is the common goal of PPPM and translational medicine to find the solution for the problem we present in our review. Both, translational medicine and PPPM in parallel, essentially need accurate surrogates for misleading animal models. This study was therefore undertaken to provide shreds of evidence against the validity of animal models. Limitations of current animal models and drug development strategies based on animal modeling have been systematically discussed. Finally, a variety of potential surrogates have been suggested to change the unfavorable situation in medical research and consequently in healthcare.


Predictive preventive personalized medicine Future healthcare Animal modeling Disease modeling Clinical trial failure Translational medicine Chronic diseases Cardiovascular disorders Cancer Toxicology Drug discovery Drug development 





American College of Surgeons


Acquired immunodeficiency syndrome


American Joint Committee on Cancer


Amyotrophic lateral sclerosis


Amyloid precursor protein


Advanced trauma life support


Azidothymidine (now renamed zidovudine, but still best known by the abbreviation AZT)


Coronary artery bypass grafting


Computer-aided drug design


Cystic fibrosis


Coronary heart disease


Chronic unpredictable mild stress model


Cardiovascular disease


Diabetes mellitus


The European Association for Predictive, Preventive and Personalised Medicine




Estrogen receptor


U.S. Food and Drug Administration


High-density lipoprotein cholesterol


Human epidermal growth factor receptor 2


Human immunodeficiency virus


Idiopathic pulmonary fibrosis


Lethal dose, 50%, median lethal dose


Myocardial infarction


Neurological, neuropsychiatric, and neurodegenerative diseases


Oral Contraceptive


Predictive, preventive, and personalized medicine


Progesterone receptor


Quantitative structure activity relationships


Randomized controlled trial


Severe acute respiratory syndrome


Superoxide dismutase 1


Effector memory T cell


Theralizumab (also known as TGN1412, CD28-SuperMAB, and TAB08), a humanized monoclonal antibody that not only binds to, but is a strong agonist for, the CD28 receptor of the immune system’s T cells


Tumor, nodes, and metastases


Transactive response DNA-binding protein 43


X-linked severe combined immunodeficiency



Authors would like to thank Dr. Hilda Samimi and Dr. Mahmood Naderi for their scientific advices.

Author contribution

Idea: Soroush Seifirad (SS) and Vahid Haghpanah (VH)

Literature review: SS

Drafting article: SS except for suggestions which were written by both SS and VH

Final review and approval: SS and VH

Compliance with ethical standards

Consent for publication

Not applicable.

Ethical approval

Not applicable. This is a theoretical appraisal; neither patients nor animals were involved in this research.

Competing interests

The authors declare that they have no competing interests.


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Copyright information

© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2019

Authors and Affiliations

  1. 1.PERFUSE Study Group, Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA
  2. 2.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran

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