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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
Research

Abstract

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.

Keywords

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 

Abbreviations

3TC

Lamivudine

ACS

American College of Surgeons

AIDS

Acquired immunodeficiency syndrome

AJCC

American Joint Committee on Cancer

ALS

Amyotrophic lateral sclerosis

APP

Amyloid precursor protein

ATLS

Advanced trauma life support

AZT

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

CABG

Coronary artery bypass grafting

CADD

Computer-aided drug design

CF

Cystic fibrosis

CHD

Coronary heart disease

CUMS

Chronic unpredictable mild stress model

CVD

Cardiovascular disease

DM

Diabetes mellitus

EPMA

The European Association for Predictive, Preventive and Personalised Medicine

EPO

Erythropoietin

ER

Estrogen receptor

FDA

U.S. Food and Drug Administration

HDL-C

High-density lipoprotein cholesterol

HER2

Human epidermal growth factor receptor 2

HIV

Human immunodeficiency virus

IPF

Idiopathic pulmonary fibrosis

LD50

Lethal dose, 50%, median lethal dose

MI

Myocardial infarction

NNND

Neurological, neuropsychiatric, and neurodegenerative diseases

OCP

Oral Contraceptive

PPPM

Predictive, preventive, and personalized medicine

PR

Progesterone receptor

QSAR

Quantitative structure activity relationships

RCT

Randomized controlled trial

SARS

Severe acute respiratory syndrome

SOD-1

Superoxide dismutase 1

TEM

Effector memory T cell

TGN1412

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

TNM

Tumor, nodes, and metastases

TP-43

Transactive response DNA-binding protein 43

X-SCID

X-linked severe combined immunodeficiency

Notes

Acknowledgments

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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