The Present and Future of Medical Publication

Sunny Dzik, MD Service, Massachusetts General Hospital, Harvard Medical School, Boston Editor, Reviews Financial Disclosure:

Stipend from Elsevier Publishing for my role as Editor of Transfusion Medicine Reviews.

I have no other conflicts of interest to declare. For 20 centuries In the 15th Century Moveable type ! 1450

Source: wikipedia Henry Oldenburg

1st Scientific Editor

Introduced the idea of scientific peer review

Source: insights.uksg.org For 20 centuries In the 15th Century Now

1450 The Internet is changing all aspects of medical publication

1. Business model for publishers.

2. Metrics to ”rank” scientific publication.

3. Opportunity for fraud, plagiarism & the ability to catch it.

4. Dimensions of information transfer.

5. Sheer volume of information and importance of quality. 1. Business Models for Medical Publication

Individual subscription model becoming extinct.

Publishers sell a ‘bundle’ of journal titles to libraries.

Users access individual articles on line.

Packaging articles in “volumes” with “page numbers” may seem increasingly out-of-date.*

*DOI = digital object identifier

How Medical Libraries Used to Store Articles Medical College Library in Tanzania

kcmuco.ac.tz/home/ ‘Open Access’ publishing

. Article is made freely available to all online immediately after acceptance. . Author, Institution, or Grant Funds pay an ‘article publication fee’. . Some journals publish exclusively open access (PLOS, Biomed Central). . Most journals are mix of subscription and open access options. . Open access can offset subscription costs.

Devised at the University of Leiden

Vox Sanguinis: Open access $3300 Free self-archive access after 12 months

Transfusion: Open access $3900 Free self-archive access after 12 months

Transfusion Medicine Reviews: Open access $2500 Free self-archive access after 12 months Globally: Funders Embrace Open Access (but usually do not pay for it)

Image courtesy of Elsevier 2. Metrics try to “rank value” (Score of a journal) Citations in 2017 from items published in 2015 & 2016 Impact Factor 2017 A A Impact Factor = B 2014 2015 2016 2017 2018

B Transfusion Medicine Reviews Number of published documents from journal in 2015 & 2016 In 2017, 222 citations for TMR A articles published in 2015 & 2016 222 = = 4.11 B TMR published 54 papers 54 in 2015 & 2016 Source: 2017 Journal Citation Reports, Clarivate Analytics Alternative metrics (score of an article)

. “Altmetrics” provide a score for each article based on media and social media activity. (The social chatter need not be positive !)

Altmetric

Citations versus Downloads: Citations versus Downloads: 100 manuscripts from Transfusion Medicine Reviews

7 0 0 0 Rx of Glanzmann’s Thrombastenia (2016) Patient Blood Management (2017) 6 0 0 0

5 0 0 0

s Review of MT ratio’s (2015) d

a 4 0 0 0

o

l n

w 3 0 0 0

o D

2 0 0 0 Mesenchymal stroma cells (2016)

CAR T-cells (2016) 1 0 0 0

0 0 5 1 0 1 5 2 0 2 5 3 0 3 5

Rationale for INFORM trial (2016) C ita tio n s Journals serve both authors and readers Transfusion Medicine Reviews receives >100,000 downloads/year from 100 different countries. Who is writing ? Who is reading ?

Authors for Transfusion Medicine Reviews Downloads for Transfusion Medicine Reviews

Image courtesy of Elsevier Publication Activity for TMR (2013-2017)

The color reflects the share of publications in TMR, in comparison to the other journals (data normalised to account for journal sizes).

Blue  TMR has very low share of the publications using this term…. Yellow, orange and red  TMR publishes a higher share on this topic.

Image courtesy of Elsevier 3. Fraud, conflict of interest, plagiarism Brian Wansink, PhD

Head of the Food and Brand Lab at Cornell University, Wansink announced (Sept ‘18) that he would retire from the university.

48 hours earlier, JAMA had retracted six of Wansink's studies, after Cornell told the JAMA Editors that the university could not vouch for the validity of his studies. Scientific Fraud Retractions from PubMed (1980-2010) 8 Fraudulent research

Fake peer reviewer 6 Violation of Authorship

4 Duplicate publication

2 Conflicts of Interest ($$) Retractions / / 100k pubs Retractions Plagiarism

1980 1985 1990 1995 2000 2005 2010 Year Copyright infringement

Conflict of Interest: Financial fraud Dr. José Baselga, the chief medical officer of Memorial Sloan Kettering Cancer Center, resigned on Thursday amid reports that he had failed to disclose millions of dollars in payments from health care companies in dozens of research articles.

Dr. Baselga, a prominent figure in the world of cancer research, omitted his financial ties to companies like the Swiss drugmaker Roche in prestigious medical publications like the New England Journal of Medicine and The Lancet. He also failed to disclose any company affiliations in articles he published in the journal Cancer Discovery, for which he serves as one of two editors in chief.

Source: NY Times Right to Copy (copy-right) and Paste

Plagiarism: the practice of taking someone else’s words or ideas and presenting them as your own.

Copyright infringement: the unauthorized use of copyrighted material, such as text, photos, videos, music, software, and other original content.

When your work is published, you sign-over the copyright to the publisher. You no longer retain it.

You cannot copy even your own prior words and re-present them without citation. Transfusion Medicine Reviews uses “iThenticate”

4. Dimensions of Information Transfer: Publishers are competing for innovations… . Graphical abstracts, maps, open data, 3D models, multimedia files – and more. . Tools like ‘virtual microscopes’ allows readers to gain more insight into your work. . 3D data visualizations (cell surface antigens, immunohematology, coagulation). . Audio-visual teaching in Transfusion Medicine (“You Tube” with peer review).

Devised at the University of Leiden

Graphical Abstracts Google Maps 3D models Virtual Microscope AudioSlides Graphical Abstract If poorly done, a step backwards… Publishers want you to be able to promote your research Example: Share Links from Elsevier: After acceptance, you get a email with a link, which you can send to anyone. Those who click on the Share Link within a 50-day period go directly to the full article with no sign up or registration required (free).

Source: Elsevier and Twitter Publishers will facilitate mechanisms for data sharing…

Mendeley Data

Data in Brief

The International Committee of Medical Journal Editors (ICMJE) believes there is an ethical obligation to responsibly share data generated by interventional clinical trials because trial participants have put themselves at risk.

Clinical trials that begin enrolling participants on or after 1 January 2019 must include a data sharing plan in the trial’s registration. 5. The sheer volume of medical information

Velterop J. Science 2015 Turning information into knowledge Too Much to read… In the digital world….Information must be “curated”

If reading for clinical care… If you are an author…. Analytical Reviews Go to original primary source (in peer reviewed journals) publications from peer-reviewed journals. Textbooks (traditional or digital)

List serves for selected articles (Transfusion Medicine Evidence Library)

Practice Guidelines (be careful) Medical Publishing: 2018 Care of patients and advance of science depends upon getting to the truth. Quality of our Profession’s knowledge depends on independent peer review. Authors must take their ethical responsibilities very seriously. Journal Editors serve both authors and readers. The opportunity to share knowledge has never been better.

How to review a paper

Richard Kaufman MD Editor-in-Chief, TRANSFUSION

Oct. 13, 2018 Faculty Disclosure (In compliance with ACCME policy, AABB requires the following disclosures to the session audience) • None

www..org 2 Objectives

After attending this activity, participants will demonstrate the ability to: • Discuss reasons to accept or reject a request to review a paper. • Describe key elements to consider when reviewing. • Explain the structure of a good review.

www.aabb.org 3 You’ve just been invited to review a paper

www.aabb.org 4 You’ve just been invited to review a paper

www.aabb.org Mdbcomm.com 5 You’ve just been invited to review a paper

www.aabb.org Someecards.com 6 You’ve just been invited to review a paper

www.aabb.org Yiddishwit.com 7 You’ve just been invited to review a paper

www.aabb.org Knowyourmeme.com 8 You’ve just been invited to review a paper

• Someone values your expertise. • You will learn something new. • Your writing will improve. • You will help the field. • Someday, an anonymous person will agree to review your paper.

www.aabb.org Dailytelegraph.com 9 When should you decline a review?

• The topic is outside your scope of expertise. • You cannot do the review in the allotted time. • You have a meaningful conflict.

www.aabb.org Tokyoing.net 10 So you’ve decided to do a review.

Consider: 1. What is the question? 2. Is the question important? 3. How was the question answered? 4. Are the conclusions supported by the results?

www.aabb.org esfsciencenew.wordpress.com 11 What is the question?

www.aabb.org 12 What is the question?

Example: Do pathogen-reduced prevent bleeding as effectively as conventional platelets?

www.aabb.org 13 What is the question?

Clinical Research Question: Population Among hospitalized adult patients with AML Intervention does transfusing pathogen-reduced apheresis platelets Comparison versus standard apheresis platelets Outcome increase days of Grade 2 or higher bleeding Time during the period of thrombocytopenia?

www.aabb.org 14 Is the question important?

www.aabb.org Thoughtgallery.org 15 Is the question timely?

www.aabb.org Thoughtgallery.org 16 How was the question answered?

www.aabb.org Articlesweb.org 17 Could the study as designed answer the question? Example: Do pathogen-reduced platelets prevent bleeding as effectively as conventional platelets? Possible study designs: • In vitro study of aggregation • RCT of 800 trauma patients • RCT of 800 AML patients having central lines placed • RCT of 800 AML patients with thrombocytopenia from chemo

www.aabb.org 18 Could the study as designed answer the question? Example: Do pathogen-reduced platelets prevent bleeding as effectively as conventional platelets?

The approach should fit the question.

• RCT of 800 AML patients with thrombocytopenia from chemo

www.aabb.org 19 Do the Methods clearly describe what was done?

www.aabb.org cartoonaday.com 20 Were experiments repeated sufficiently?

www.aabb.org 21 Were experiments repeated sufficiently?

www.aabb.org 22 Do the controls permit the results to be interpreted?

Mouse model of platelet immune refractoriness

H-2q lymphocytes Anti-H-2q • Label MHC-mismatched (H-2q) PLTs • Transfuse into immunized mouse • Measure PLT survival

H-2b

www.aabb.org Arthur 2016, Blood 127:1823 23 Do the controls permit the results to be interpreted?

MHC-mismatched PLT transfusion

What if the PLTs 100 were cleared due to

an intrinsic PLT defect? % PLT survival PLT %

0 Imm. mice www.aabb.org Arthur 2016, Blood 127:1823 24 Do the controls permit the results to be interpreted?

MHC-mismatched PLT transfusion

What if the PLTs 100 were cleared due to

an intrinsic PLT defect? % PLT survival PLT %

0 Imm. mice NON-imm. mice www.aabb.org Arthur 2016, Blood 127:1823 25 Were the study groups balanced?

PLT transfusion No PLT transfusion Characteristic P n = 44 n = 64 Mean age (yrs) 74.3 75.4 0.63 Male 52% 50% 0.82 Aspirin (%) 86% 89% 0.45 Etiology = fall (%) 86% 84% Clopidogrel (%) 52% 20% 0.0005

www.aabb.org Washington 2011, J Trauma 71:358 26 Were the study groups balanced?

PLT transfusion No PLT transfusion Characteristic P n = 44 n = 64 Mean age (yrs) 74.3 75.4 0.63 Male 52% 50% 0.82 Aspirin (%) 86% 89% 0.45 Etiology = fall (%) 86% 84% Clopidogrel (%) 52% 20% 0.0005

www.aabb.org Washington 2011, J Trauma 71:358 27 Are the data presented clearly?

www.aabb.org Junkcharts.com 28 Good figure

www.aabb.org 29 Bad figure

Day of platelet storage

www.aabb.org 30 Good table

Table 1. Hemoglobin levels among apheresis platelet donors Donors Gender Donations/year Hemoglobin (g/dL) P value (n) (% male) (n) median [range] 120 55 1-5 14.2 [12.6 - 16.3] REF 111 54 6-10 14.0 [12.5 – 17.2] 0.24 68 71 11-15 14.1 [12.8 - 16.0] 0.36 60 82 16-20 14.3 [12.6 -17.2] 0.10 45 90 20-24 14.1 [12.5 – 16.7] 0.45 REF, reference

www.aabb.org 31 Bad table Table 1. Hemoglobin Donors Male donors Donations/year P value median [range] 44 18 1-2 14.212 [12.634 - 16.330] REF 35 13 3-4 14.013 [12.536 – 17.231] N.S. 51 40 5-6 14.111 [12.837 - 16.034] N.S. 29 19 7-8 14.321 [12.644 -17.219] N.S. 237 122 9 or more 14.124 [12.490 – 16.719] N.S.

www.aabb.org 32 Good sentence

Platelet units stored for 3-5 days caused all of the observed septic transfusion reactions.

www.aabb.org 33 Bad sentence Interestingly, our evaluation indicated that, indeed, units of platelets which had been stored at room temperature within the blood bank for a longer temporal duration (i.e. for 3, 4, or 5 days prior to their being issued to the primary clinical service for transfusion) had served as the proximal causative factor in 100% of clinically evident acute septic transfusion reactions either initially reported by the primary clinical service (i.e. detected by passive surveillance) or identified retrospectively following review of the medical records.

www.aabb.org 34 Reviewing is not proofreading

1. Introduction, Page 3, line 10: “gram-positive” should be capitalized. 2. Introduction, Page 3, line 13: “in-vitro” should not be hyphenated. 3. Introduction, Page 3, line 14: “gram negative” should be capitalized and hyphenated. 3. Introduction, Page 3, line 22: eliminate the apostrophe after “platelets” 4. Introduction, Page 4, line 5: should be “their,” not “there.” 5. Introduction, Page 4, line 11: “radically” is misspelled (extra “d”). Please fix. 6. Methods, Page 5, line 8: “patient population” should not be capitalized. 7. Methods, Page 5, line 14: ”B. cereus” should be italicized. 8. Methods, Page 5, line 15: “phlegmatic” is misspelled (and antiquated.) 9. Methods, Page 5, line 16: “obsidian” is misused here. Did you mean “obsequious?”

www.aabb.org 35 Reviewing is not proofreading

There were numerous grammatical and spelling errors throughout the text.

www.aabb.org 36 Are the conclusions supported by the results?

P = 0.0001 Inpatient deaths (n) deaths Inpatient

www.aabb.org 37 Are the conclusions supported by the results?

Conclusion: • RBC transfusions cause death in ICU patients. • RBC transfusions appear to cause death in ICU patients. • A restrictive RBC transfusion strategy improves survival in ICU patients. • ICU patients who did not receive blood products had higher survival. • ICU patients who received 3 or more RBC units had a higher rate of inpatient death compared with ICU patients who received 0-2 RBC units.

www.aabb.org 38 Writing your review

• Confidential comments to Associate Editor – Recommendation on acceptance/rejection goes HERE • Comments to Author – General Comments • Briefly recap question, hypothesis, approach, key results, conclusion • Overall assessment – Specific Comments • Starting with the Title, give comments in sequence • Give page/line numbers

www.aabb.org 39 Conclusions

• When reviewing, ask yourself penetrating questions. • These apply universally: 1. What is the question? 2. Is the question important? 3. How was the question answered? 4. Do the results support the conclusions?

www.aabb.org 40 Conclusions

• If a paper is POOR, point out the major flaws. – Think critically, comment constructively. – “This paper would be improved by . . .” – The Golden Rule applies.

www.aabb.org 41 Conclusions

• If a paper is GOOD, help the authors make it better. – The more clear a paper is, the better. – Be constructive. – The Golden Rule applies here too.

www.aabb.org 42 Resources on reviewing

Publons Academy: https://publons.com/blog/publons-academy/

•Heddle NM and Ness PM. Reviewing manuscripts: tips and responsibilities. Transfusion 2009;49:2265-2268.

www.aabb.org 43 Thanks!

www.aabb.org 44 The ‘Nuts and Bolts’ of Publishing: the Elements of a Successful Paper

Dana Devine, PhD Chief Scientist, Canadian Blood Services Editor in Chief, Vox Sanguinis Disclosure

• Research support from Macopharma, TerumoBCT and Hemanext

• Editor in chief, Vox Sanguinis; financial support from Wiley WRITTEN FORMS OF SCIENTIFIC COMMUNICATION

• Original Articles • Full manuscripts • Short communications • Case reports • Survey Summaries • Meeting reports • Review Articles • Letters to the Editor The Pre-Work: Learn by observation

Consider when reading papers which papers were particularly well done (positive lessons). Also consider what is wrong with papers that are painful to read (negative lessons). Pay attention to the type and amount of data that are in a good paper and how it flows logically to tell the story. In the Beginning…. • There is the project design… • Appropriate controls • Application of statistical principles including power calculations • Analytical methods • Once the study starts, begin the writing process • Choose an informative provisional title Good papers arise from • Create an outline for the paper to well-designed studies help identify gaps in the story

5 Improving the Chance of Success

Quality of the science Choice of a compatible journal for the topic and impact of the study Obsessive attention to detail in the preparation of the manuscript. The devil really is in the details….reviewers are influenced by the quality of the paper. Mistake-free manuscripts help keep reviewers focused on the content. Where to publish?

You can get some ideas by looking at journals that published similar studies. Is your work of general interest or targeted to a more specific audience? Read the journal’s website for mandate and directions to potential authors. It is best to decide on your target journal before you write the paper. The Basics

Read the instructions – every journal wants something slightly different. Failure to follow the rules may result in immediate technical rejection of the manuscript, and almost always results in a delay in the review process. Word limits (include all words unless otherwise instructed) Reference format

8 The Title – Your first impression

Be informative. Be concise. Avoid abbreviations.

If possible provide the study outcome in the title. • “Use of fresh red blood cells does not improve transfusion outcome” versus • “The effect of storage time on transfusion outcome” The ‘IMRAD’ Format

Most biomedical journals use the IMRAD format • Introduction • Methods • Results • And • Discussion Almost all journals require an abstract as well. Telling the Story

• Why? • How? • What? • Who cares?

11 The Abstract

Write the abstract LAST; it must be an accurate reflection of your paper which therefore is written FIRST. Abstract format is often specific to the journal. Set the stage in 2 or 3 sentences that convey why the topic is important. Catch the reader’s Provide a brief description of the attention. It may be your methodology, summarize the only chance. results with data, and state conclusions. 12 The Introduction

This section provides the reader with an understanding of why you did the study and why the work is important. Provide the relevant background to your story. It should not be a complete review of the literature. It should cite the specific literature required to help you set the stage for your scientific story. Avoid excessive self-citation; it annoys reviewers. The introduction usually ends with a brief description of the aims and rationale of your study and a concise statement of the conclusion. The Methods This section needs to provide sufficient information about the techniques and experimental design that a competent worker could repeat the study. Do not cut corners. Citation of other papers describing a method is acceptable, but indicate any alternations that you made.  This section also contains the details of data handling and analysis. Follow guidelines if reporting a clinical

study (CONSORT, PRISMA, STROBE) 14 The Results • Be clear. • Provide real data and analysis • Numbers • Statistics • Detailed findings • Be sure statements and results are consistent; avoid exaggeration and repetition. • Do not create a table or figure for what could be said in a sentence. • If you do use tables or figures, make sure they will be clear when reduced for publication, and that all abbreviations are defined in the legend or footnotes.

15 The Discussion • What are the results telling you? • What’s the message you want the reader to take away? • Do not give more importance to your findings than they deserve. • Minimize speculation in areas where you lack direct data.

16 Authorship • ICMJE criteria state that authors must show: • Substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of the data; AND • Drafting the work or revising it critically for important intellectual content; AND • Final approval of the version to be published; AND • Agreement to be accountable for ALL aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. • Many journals now require an explanation of author contributions in the Acknowledgments section. Writing Pitfalls

• Lack of organization: • Your document should be neat, clear in meaning and free from errors. • Define all abbreviations. • Watch for jargon. • Number the pages. • Failure to comply with style requirements. Make sure you provide correct • Poor use of the language of attribution of others’ work. Most publication. journals screen submissions using anti-plagiarism software.

18 Submitting the manuscript

• Most journals have an on-line submission process. Sign up when you first start writing. • Most ask for preferred referees. Many give you the opportunity to indicate if you have referees you prefer are not used. • A cover letter should be included covering: • That the paper is not under review elsewhere, and has not been previously published. • That all authors have read and approved of the manuscript as submitted.

19 Questions?

20