TRANSLATIONAL EPIDEMIOLOGY

Dr. Adhiraj Mishra, Research Scholar Dr. BR Singh, Head

Division of Epidemiology Indian Veterinary Research

Institute, Izatnagar& Director CCS NIAH,

Baghpat

“Knowing is not enough; we must apply”

“Willing is not enough; we must do.”

Johann Wolfgang von Goethe

Why Translation ?

(NIH, 2013)

Defining Translational Epidemiology(1)The study of distribution and determinants of

the health related events in a population is Epidemiology

(2) Application of this study to control health related events is Translational Epidemiology .(Moyses Szklo, 2013)

Translational Research vs. Translational Epidemiology

• Translational Research transforms scientific discoveries arising out from laboratory into clinical application to reduce incidence, morbidity and mortality.

• Translational Epidemiology is the effective transfer of new knowledge resulting from epidemiologic studies (including trials) into planning of population wide and individual level disease control programme and policies.

(Moyses Szklo, 2013)

Bench & Bedside to Population

Translational Epidemiology is stretching the discoveries of TR beyond the bedside to reach the population.(American College of Epidemiology, 2006)

Bench & Bedside to Population

History

Adopted since mid 1800 when the Broad Street Pump was closed after John Snow traced Cholera epidemic to this pump. (Cameron D, Int J Epidemol 1983)

Phases of Translational Research

Candidate Application

Evidence Based recommendati

on of policy

Practice & Control

Programs

Population Health-Disease

Burden

Scientific Discovery

T2T1

T0

T4

T3

Knowledge

Synthesis

Bench-to-Bedside Valley

T0

T-0-Scientific Discovery

• New knowledge insight into the causes, pathobiology, or natural history of disease.

• It includes the pre clinical and animal studies.

• Epidemiology describes the health outcomes by APT, determinants and risk factors.

(Khoury MJ, Am J Epidemiol, 2010)

T-1- Discovery to Health Application

Discovery

Methods in T-1 Epidemiology• Evaluating interaction

(Epidemiological Triad, Wheel & Web)• Diagnostic Testing

(Sensitivity, Specificity, Predictive Values, Likelihood Ratios, Area Under the curve & ROC)

• Proof of Concept (POC):Establishes the safety of drug candidates in the target population and explore the relationship between the dose and desired activity.

• First in Human (FIH)Trials:Experiences with animal testing is extended to human subjects for the first time.  

• Phase -1 Clinical Trial:First stage of testing in human subjects in a group of 20–100 healthy volunteers. Assessment of safety, tolerability, pharmacokinetics and pharmaco-dynamics and dose ranging of a drug.

• Human Volunteer:They advance medical knowledge, provide scientific information important to developing new treatments for disease.

• Health Economics: Cost Effectiveness.

Methods in T-1 Epidemiology

T-2- Health Application to Evidence Guidelines

Methods in T-2 Epidemiology• Evidence based recommendations:

It uses the experience of a population of patients reported in the research literature to guide decision making in practice. It requires the application of population-based data to the care of an individual patient.

• Observational & Experimental Studies:It includes the cross sectional, cohort, case control, RCTs and Non randomised trials to determine the clinical utility.

• Phase III Clinical TrialsAssesses the effectiveness by Randomized controlled multicenter trials on large patient groups (300–3,000) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment.

Methods in T-2 Epidemiology

T-3- Practice Guidelines to Health Practice

Methods in T-3 Epidemiology• Implementation Research:

Scientific inquiry into questions concerning implementation—the act of carrying an intention into effect, which in health research can be policies, programmes, or individual practices (collectively called interventions).

• Dissemination Research:Examination how health promotion interventions can be effectively created, packaged, transmitted, and adopted.

• Phase IV Clinical Trials:Post marketing surveillance trial. Phase IV trials involve the safety surveillance (pharmaco-vigilance) and ongoing technical support of a drug after it receives permission to be sold.

Methods in T-3 Epidemiology

T-4-Health Practice to Improved Health

Methods in T-4 Epidemiology•Surveillance Research.•Real World Outcome research:It studies the end results of medical care. It evaluates the results of the health care process in the real-life world of the doctor’s office, hospital, health clinic and even the home.•Feedback Mechanism.•Social Determinants of Health:These are the economic and social conditions – and their distribution among the population – that influence individual and group differences in health status.

Methods in T-4 Epidemiology

Drivers of Translational Epidemiology

(Larn T K et al, AACR, 2013)

Discoveries

Technology• ‘omics’ e.g proteomics,

epigenomics, metabolomics.

• Digital epidemiology

• Communication science• Infodemiology.

Collaboration & Team Science• Concerted effort• Team Science initiatives

across disciplines.• Well characterised cohort

studies with large sample size.

Multilevel Analysis & InterventionsMultilevel model with interaction between person(biologic, risk factor, socio-demographic characteristics), the provider, family and social supports, organization or practice setting and local community environment.

.

Knowledge Integration

• Knowledge Management

• Knowledge synthesis

• Knowledge translation

Translational Epidemiology & One Health

• Interface between experts of human, animal & environmental field.

• Vertical One Health Process.

• Advances in current diagnosis & treatment

(Tang Yi-Wei, Vet Microbiol, 2013)

Challenges in Translational Research

• Basic Research is not clinically relevant.• Shortage of translational investigators.• Inadequate collaborative approach.• Poorly integrated activity from academia

to private sector and industry.• Inadequate financial support.

• Regulatory impediments to translation.• Inflexible clinical trial designs.

(Pober SJ et.al, 2001)

Traversing the Valley of Death

Provide access to adequate funding.Adequate potential commercial market &

industry partner. Inference from human & animal data about

likely safety and efficacy.Remove physical barriers blocking

collaboration.Restructure the academic environment.Provide support for administrative

facilitation & regulatory compliance.(Coller BS et.al, 2009)

TE Research Institutes in India

Summary

• Epidemiology is a fundamental science for translating basic discoveries into population health benefits.

• TE provides the key data needed to document what we know and what we do not know, and what works and what does not work, thus influencing further research, practice, and policy development.

• TE is a necessary ingredient to move specific discoveries from research into practice in an evidence based fashion.

Recommendations

• Bio-medical Research Institutes should have clinic facility.

• All research institutes & academia should adopt translational models for research.

• Funding should be balanced between clinical & population based research.

• Interdisciplinary collaboration & Team work.