KATRINA L. KELNER, PHDEDITOR, SCIENCE TRANSLATIONAL MEDICINESCIENCE FAMILY OF JOURNALS

KIKI FORSYTHE, MLSSENIOR PUBLISHER RELATIONS SPECIALISTSCIENCE FAMILY OF JOURNALS

Defining and Publishing Translational

Medicine

Translational and Precision Medicine

The expanding Science family of journals (Kiki Forsythe)

Publishing in Science journals

Defining Translational Research: Standard Definition

BASIC

BIOMEDICAL

RESEARCH

PRECLINICAL RESEARCH

CLINICALTRIALS

IMPLEMENTATION

BENCH BUSINESS BEDSIDE

Defining Translational Research:More Complicated Definition

Research that moves basic and preclinical biomedical or engineering science discoveries toward improved patient care

Clinical observations that are moved back into the research lab for mechanistic studies

The use of research findings to inform policy changes that affect community health and heath care

Translation: The Road is Long

SLOW:

EXPENSIVE:

HIGH FAILURE RATE:

NUMBER OF NEW DRUGS:

PROBLEM:

Average time to approval, 10 y

Cost per successful drug: $4B

1 in 40 (not 1 in 10) drug candidates reach clinic

27 FDA drug approvals in 2013(only 9 first in class)

Limited access to patients except during clinical trials

KNOWLEDGE

INNOVATION

REGULATORY

POLICY

S

Let’s give it a try. If all else fails, Sara has a corkscrew.

KNOWLEDGE GAP:

We don’t know as much about human biology as we thought we did

We must decipher the natural histories of human diseases and use this knowledge to select therapeutic targets and approaches

Progress requires investigations at the interfaces of established and emerging disciplines

BEDSID

INNOVATION GAP:

• Fear of risk

• Lack of funding; rewards for safe science, not new ideas

• Pharmaceutical and Biotech companies must satisfy shareholders and make profits

• “Ultimately, translational research requires a leap of faith because … there is always the risk of unanticipated adverse events.”

--Christopher Breuer, MD, Deputy Vice Chair of Research and Director, Tissue Engineering,

The Ohio State University

REGULATORY GAP:

Regulation is a bottleneck VS Regulation protects the public

Do we need to approve drugs and devices faster or be more vigilant about keeping potentially dangerous drugs off the market?

Challenge: We could do both at the same time if we could learn how to accurately predict, from preclinical data, the human health risks associated with a new product

REGULATORY GAP:

What Is the Greatest Regulatory Challenge in the Translation of Biomaterials to the Clinic?

G. D. Prestwich et al., What Is the Greatest Regulatory Challenge in the Translation of Biomaterials to the Clinic?. Sci. Transl. Med. 4, 160cm14 (2012).

POLICY GAP:

stm.sciencemag.org/site/misc/current_policy_collection.xhtml

• FUNDING (e.g., ideas for early-venture funding)

• EDUCATION (e.g., how to train the next generation of translational scientists)

• REWARD SYSTEMS for team science (industry and academics)

• GLOBAL HEALTH ISSUES (large philanthropic entities, the Gates Foundation)

• REGULATORY OVERHAUL (requires government intervention)

• Make available to the world's scientists screening facilities, validated animal disease models, and chemical compound libraries

• Earlier access to patients • Facilitate drug repurposing

B. Onaral, Emerging Economies, Enduring Partnerships. Sci. Transl. Med. 4, 158ed8 (2012). Podcast: stm.sciencemag.org/content/4/158/158pc7.abstract

Solutions

• Build worldwide innovation networks with diverse expertise

• Make available to the world's scientists screening facilities, validated animal disease models, and compound libraries

• Build worldwide innovation networks with diverse expertise 

B. Onaral, Emerging Economies, Enduring Partnerships. Sci. Transl. Med. 4, 158ed8 (2012). Podcast: stm.sciencemag.org/content/4/158/158pc7.abstract

USAEurope

China

Collaboration

PUBLIC AND PRIVATE PARTNERSHIPS“Share everything … Play fair.”

--Robert Fulghum

DATA SHARING

Sharing of knowledge drives science and innovation. It fosters cross-pollination, an essential driver of creativity

A proprietary culture threatens to stall the engine that has given us so many valuable treatments

Industry, academia, foundations, and government need to engage in collaborations early in the research process

Expand the precompetitive space!

B. Onaral, Emerging Economies, Enduring Partnerships. Sci. Transl. Med. 4, 158ed8 (2012). Podcast: stm.sciencemag.org/content/4/158/158pc7.abstract

Successes

Cell-based Therapeutics

TumorImmunotherapy

Engineered microbes

iPSCs

Engineered microbes

NEU

RO

PR

OS

TH

ETIC

S

IMAGING THE LIVING HEART

Nanoparticle imaging and corresponding diagnostic modalities

GENOMIC MEDICINE

PRENATALDIAGNOSIS

GENETIC DISEASES

INCOMPLETE PENETRANCE

DISEASE SUSCEPTIBILITY

PREDICTIVE ANIMAL MODELS

CANCER

Precision Medicine

Emerging in the last 5 years

……an innovative approach to disease prevention and treatment that takes into account individual differences in people’s genes, environments, and lifestyles.  Precision medicine gives clinicians tools to better understand the complex mechanisms underlying a patient’s health, disease, or condition, and to better predict which treatments will be most effective.

United States of America President Obama announces

the Precision Medicine Initiative Jan 30 2015

Epilepsy patients who carry an HLA-B*1502 gene should not receive the antiepileptic drug carbamazepine. This genetic marker predicts with high certainty that they will react to the drug with the deadly skin-blistering side effect “Stevens–Johnson syndrome” Another drug should be chosen.

The Genetics of the Individual Patient Guides Drug Selection

Carbamazepine, HLA-B*1502 and risk of Stevens–Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. PB Ferrell and HL McLeod, Pharmacogenetics 9, 1543 (2008)

Precision Medicine

Cancer leads the way for Precision Medicine

Lung cancer Some patients recover, some do not

Gefitinib

Gefitinib

Two types of lung cancer Two precision treatments, all recover

Bisphosphonate plus rapamycin

EGFR +

K-RAS+

Alexis Borisy (left) and Michael Pellini founded Foundation Medicine to determine the genetics of cancers for individual patients

A patient with salivary gland cancer who had failedconventional treatment sent cells from his tumor toFoundation Medicine for testing. They were found toshow overactivity in HER2, a gene often defective inbreast cancer. This result suggested to the patient’sdoctors that his cancer would respond to Herceptin,a drug often prescribed for breast cancer patients

Remote continuous vital sign monitoring via iPhone. Delivers real-time data about the vital signs of any patient who is in a hospital intensive care unit to a doctor’s or nurse’s smart phone.

Published by AAAS

Digital Medical Devices

Another example ofpersonalized medicine for cancer:

Inject many drugs into aTumor to find the most effective

Other Precision Medicine Approaches

Personalized pharmacokinetics

Companion diagnostics for precision therapies

Nanotechnology for targeted therapies

Submitting to the Science Family of Journals

Physics

Ecology: Cave fish without eyes

Materials Science

Biomedicine

Magazine News

Research Articles

Print and online

Shorter format

Interdisciplinary Science

Open AccessOnline onlyResearch ArticlesFull papersLong format

Comparing the four Science journals

Staff editors and Board of Reviewing Editors

Peer review for top qualityReject, revise, accept

SUBSCRIPTION via INSTITUTIONPAPERS FREE AFTER 12 MONTHS

Academic editorsPeer review for top qualityReject, revise, accept

OPEN ACCESS via AUTHOR FEEPAPERS FREE IMMEDIATELY

Submissions and Acceptance Rate

Submissions/ >11500 >700 >2600 3000++ year

Acceptance 6% 19% 10% 16%

Papers/year ~800 ~150 ~250 ~250 to 500++

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How to Publish in the Science Journals is NOT a

secret Read the Science Journals

Become a trusted, critical reviewer for the Science Journals

Work on important problems

Know when you have a reasonable result worthy of publication in a high-profile journal

Present the results of your work in an unbiased, dispassionate manner

Get some honest advice from impartial critics prior to submission

WHICH JOURNAL IS RIGHT FOR MY RESEARCH?

READ THE JOURNALS

BE FAMILIAR WITH WHICH JOURNALS PUBLISH PAPERS IN YOUR FIELD

LEARN WHAT MAKES A GOOD PAPER

ASK YOURSELF THESE QUESTIONS:

Is your finding a big step forward with broad implications?

Will many scientists find your results exciting?

Did you apply a new technique to investigate difficult scientific questions?

Is your research in the biological, physical, or social sciences?

Is your study self-contained and suitable for the Science format?

IF YOU ANSWERED YES TO THESE QUESTIONS, YOUR PAPER MAY BE SUITABLE FOR SCIENCE.

Should I submit to Science?

ASK YOURSELF THESE QUESTIONS:

Is your finding a step forward with a broad implication?

Will many scientists find your results exciting?

Is your research in the biological, physical, or social sciences?

Does your paper require a longer format?

Does your funding agency require publication in an open access journal?

Was your paper recommended for transfer from a Science journal?

IF YOU ANSWERED YES TO THESE QUESTIONS, YOUR PAPER MAY BE SUITABLE FOR SCIENCE ADVANCES.

Should I Submit to Science Advances?

ASK YOURSELF THESE QUESTIONS:

Does your research use basic science knowledge to make real progress toward improved patient care?

Does your research apply engineering discoveries toward improvements in clinical care?

Do you have strong evidence that your findings apply to human beings?

Does your research present novel ideas or approaches?

Was your paper recommended for transfer by Science or Science Signaling?

IF YOU ANSWERED YES TO THESE QUESTIONS, YOUR PAPER MAY BE SUITABLE FOR SCIENCE TRANSLATIONAL MEDICINE.

Should I Submit to Science Translational Medicine?

ASK YOURSELF THESE QUESTIONS:

Are your results reporting a cellular or organismal signaling pathway:

that helps understanding of physiology and disease?

that helps understanding or treating disease?

that is a novel type of signaling?

with computational or modeling analysis leading to a tested prediction?

Was your paper recommended for transfer rom Science or Science Translational Medicine?

IF YOU ANSWERED YES TO THESE QUESTIONS, YOUR PAPER MAY BE SUITABLE FOR SCIENCE SIGNALING

Should I Submit to Science Signaling?

YOU CANT GO WRONG

IF YOUR PAPER IS NOT SUITABLE FOR ONE SCIENCE FAMILY JOURNAL, WE WILL HELP YOU TRANSFER TO A MORE SUITABLE SCIENCE JOURNAL

This is your chance to speak directly to the editor.

Explain the overall context of your results. What problem do they solve?

Explain why you are excited about your work.

Keep it short, preferably 1 page.

Have someone else proofread and edit it, especially if English is not your first language.

If you are re-using your cover letter from submission of the paper to another journal, don’t forget to change the name of the journal!!!

Write a good cover letter

Run your own review process

A scientist in your own specialty

A scientist in an unrelated specialty

A good editor for the English language

Think like a reviewer

43

How to Publish in the Science Journals is NOT a

secret Read the Science Journals

Become a trusted, critical reviewer for the Science Journals

Work on important problems

Know when you have a reasonable result worthy of publication in a high-profile journal

Present the results of your work in an unbiased, dispassionate manner

Get some honest advice from impartial critics prior to submission

Science Immunology

Science Robotics

Announcing!Two, new high-impact

research journals from the publisher of Science Publishing in 2016

A visible high-quality platform devoted exclusively to robotics research across the basic sciences, computer science, engineering, and medicine.

The exciting crossroads of cellular and clinical immunology where human research meets a full host of organisms.

Year Submissions

Reviewed

Published

2010 735 50 14

2011 821 59 10

2012 859 77 11

2013 1106 91 23

2014 1103 98 12

Percentage going to review is increasing

Percentage publish up to 2014 still lags global average of 6%

But 2015 is excellent year: by early September have already published more papers from China than in all of 2014.

China Publications in Science

Year Published

2010 10

2011 11

2012 13

2013 18

2014 24

Relative to 130 total papers published per year

China Publications in Science Signaling

China Publications in Science Advances

26 published (out of 176, or about 15%)

16 additional in press

10 under review

222 rejected

A vanished history of skeletonization in Cambrian comb jellies, by Ou et al.,China University of Geosciences, Beijing.

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Standing out from the crowd The past: Authors compete to get their

papers published in high-impact journals; IF of journal considered a proxy for quality of paper.

The present: Increased use of citations, altmetrics; importance on raising visibility through conventional and social media

The future: Menu of options for demonstrating impact across the basic to applied spectrum, including predictive factors based on altmetrics; more emphasis on authors getting the word out.

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Standards of conduct

The past: Variations in interpretation of what constitutes COI, contributions worthy of authorship, etc. vary internationally.

The present: Journals increasingly stipulating expectations for conduct and asking authors and reviewers to sign declarations.

The future: The scientific enterprise will truly become one international community with a common set of standards practiced globally.

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Addressing the

overburdened reviewer

system

The problem: Manuscripts undergo serial rejection from journals (down the “IF ladder”), leading to multiple rounds of review.

Solutions: Increasing use of decisions by editors

Broaden reviewer pool (please register!)

Cascading of manuscripts/reviews within journal families

Growth of 3rd party review services that provide peer review and suggest target journals appropriate for the topic/quality of the manuscript

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Trusting science

The past: Science assumed to be self-correcting. Irreproducible research would be weeded out. Fraudulent research assumed to be rare.

The present: Increasing attention on raising the standards for transparency and improving practices for open science.

The future: The scientific enterprise will truly become one international community with a common set of standards practiced globally.