Writing a Scientific Article

Henrik EkbergProfessor Transplantation Surgery, UMAS, Malmö

Associate Editor American Journal of Transplantation 2003-

Editorial Board Member:

Transplantation 2004 -

Transplant International 2004 -

Clinical Transplantation 2008 -

Journal of Transplantation 2008 - 2009

What is written without effort

is in general

read without pleasure

Samuel Johnson

The Importance of Publishing

• The nature of science:– Public– Objective– Predictive – Reproducible– Systematic – Cumulative

• Science must be communicated to exist– Published articles

are the medium– Results do not

become scientific evidence without being published

Peer Review in AJT

Editor-in-Chief

Deputy Editor

Associate Editor

Reviewer

Reviewer

Peer Review in AJT

Editor-in-Chief

Deputy Editor

Associate Editor

Reviewer

Reviewer

Decision

Rejection of submitted manuscript- various reasons

• Outright rejection: No good, or wrong journal• Rejected on priority grounds: Maybe a good study

– but not a topic of interest, or done before• Rejected, no resubmission:

– a bad study; design problems, cannot be re-written to become good

• Rejected but allowed resubmission:– no serious design problems, interesting topic, but

needs to be rewritten for language, discussion, figures, tables, etc.

Research Essentials

• Hypothesis generation and testing

• Trial design

• Statistical analysis plan

• Trial registration

• Publishing

A Brief Timeline in Scientific Publishing

• 1658: First scientific journal, Journal des Scavans

• 1812: First medical journal, the New England Journal of Medicine and Surgery

• 1860's: Pasteur introduces the IMRD format (Introduction, Materials and Methods, Results, and Discussion)

• 1957: JAMA begins to publish abstracts

• 1972: American National Standards Institute establishes IMRD as a norm for reporting scientific information

• 1978: Uniform Requirements for Manuscripts Submitted to Biomedical Journals (International Committee of Medical Journal Editors)

• 1987: Introduction of structured abstracts

• CONSORT Statement for reporting randomized trials adopted by JAMA

CONSORT

Consolidated Standards of Reporting Trials

A detailed website that includes translations in many major languages

The CONSORT Guidelines for Reporting of Clinical Trials

• Title and abstract

• Introduction

• Materials and Methods

• Results

• Discussion

• Flow diagram

The CONSORT Guidelines for Reporting of Clinical Trials

• Scientific background and explanation of rationale• Specific hypotheses and objectives• How participants are allocated to interventions, including

method used to generate and implement the random allocation sequence

• Eligibility criteria for participants • Details of the interventions intended for each group • Statistical methods used to compare groups for

outcomes, including how sample size was determined • Explanation of any interim analyses and stopping rules

The CONSORT Guidelines for Reporting of Clinical Trials

• Baseline demographic and clinical characteristics of each group

• Number of participants (denominator) in each group included in each analysis and whether the analysis was by "intention-to-treat.”

• For each outcome, a summary of results for each group, and estimated effect size and its precision (e.g., 95% confidence interval)

• Address any other analyses performed, including subgroup analyses, indicating those pre-specified and those exploratory

• All important adverse events or side effects in each intervention group

The CONSORT Guidelines for Reporting of Clinical Trials

• Interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision and the dangers associated with multiplicity of analyses and outcomes

• Generalizability of the trial findings• General interpretation of the results in the context of

current evidence

Consort advice - simple things

• Their “golden rules” for reporting numbers

for example, numbers less than 10 are written as words (e.g. nine) and larger numbers are written as the number (e.g.12)

• do not use decimal places if the sample size is less than 100

• etc

Clinical Trial Registration: Why Register?

• “The registration of all interventional trials is a scientific, ethical and moral responsibility.”

World Health Organization

• Required by law in the United States

– Efficacy trials for IND studies for serious diseases or conditions (FDA)

• Required by the International Committee of Medical Journal Editors for publishing clinical trial research

Clinical Trial Registration: Why Register?

• Increases transparency and strength/validity of scientific database

• Increases public awareness and access to trials

• Assigns trial identifier

Clinical Trial Registration: www.clinicaltrials.gov

• Eligibility: all clinical trials (observational or interventional)– Approved by Institutional

Review Board– Conforming to

appropriate national health authority

• Timing: At any time, but may be required before patient enrollment

• Requirements:– Description– Patient recruitment

information– Location and contact

description– Administrative

information

Of the Introduction, Methods, Results and Discussion sections of a scientific manuscript,

which section(s):

• Usually contain the most flaws?

• Is most often responsible for outright rejection?

• Is usually too short? • Is usually too long?

Of the Introduction, Methods, Results and Discussion sections of a scientific manuscript,

which section(s):

• Usually contain the most flaws? M

• Is most often responsible for outright rejection? M

• Is usually too short? M & R• Is usually too long? I & D

Of the following deficiencies in studies, which is most often responsible for outright rejection of

a manuscript?

Weak discussion Poor formatting

Inadequate results Weak conclusion

Lack of originality Poor methods

Poor statistical analysis Poor presentation

Of the following deficiencies in studies, which is most often responsible for outright rejection of

a manuscript?

1. Poor methods 4. Poor statistical analysis

2. Inadequate results 5. Weak conclusion

3. Poor presentation 5. Lack of originality

4. Weak discussion 6. Poor formatting

Title• Most important part of the article: the part most often

read and often the only part read

• Keep precise and brief (85-character limit is typical)

• Must stand alone: no abbreviations

• Indicate whether subjects were animals (for clinical journals)

Title• Attempt to incorporate the following elements:

– Patients– Intervention– Comparator– Outcome– Design– Setting

• Example:• Reduction of acute rejection rate by basiliximab

induction in a randomized, placebo-controlled, multicenter study after renal transplantation

Authorship and Affiliations

• Authorship credit should be based on:– substantial contributions to conception and design, or acquisition

of data, or analysis and interpretation of data; – drafting the article or revising it critically for important intellectual

content;

• List in order of greatest contribution to the work from most to least

• Some journals may require specific assignment of role of authors in the publication

• Provide full contact information for each author• Identify conflicts-of-interest

Abstract

• Purpose: to help readers decide whether to read the full article

• Second most important part of the article• Types:

– Descriptive– Structured: follow headings used by the journal

• Word limit - usually 250 words for structured abstracts

• Must stand alone• Provide 3 to 6 key words

Introduction

• Purpose: to establish the need and importance of the study

• Defines the scientific problem that stimulated the work

• Explains the technical approach or hypotheses• States the purpose and scope of the study• Introduces and defines terms and abbreviations

Materials and Methods

• Purpose: To permit readers to judge the validity of the study and to permit others to replicate the study

• Study Design – Identify the interventions and outcomes studied

• Identify the unit of analysis (e.g., rejection, renal function)• Provide measurable ("operational") definitions • Describe the methods of data collection and measurement

– Specify the type of study• Retrospective (case-control) study• Prospective (cohort or longitudinal) study• Randomized controlled clinical trial

Materials and Methods

– Describe the population studied• Define the eligibility criteria• Indicate IRB approval or compliance with Animal

Welfare Act

– Explain how subjects were assigned to groups • Define cases and controls in retrospective trials• Define exposures or diagnoses in prospective trials• Give the dates or time periods of data collection

– Identify the statistical methods • Identify at least the primary comparisons to be made• Describe how the sample size was determined • Intention-to-treat vs. on-protocol analysis• Identify the statistical software package used in the

analysis

Results

• Purpose: To tell what happened during the study and to present the findings of the study

• Explain any deviations from the study as planned

• Use Tables and Figures that are stand alone, including detailed title and legends

• Provide a schematic summary of the study to:– Show the study design – Indicate the flow of subjects throughout the study

– Account for all subjects or observations

Results

• Present the results of the study– Figure 1 Enrollment and Outcomes

Results

• Present the results of the study– Figure 1 Enrollment and Outcomes– Table 1 compares groups at baseline, i.e.

demographics– Focus on the primary comparisons first and provide:

• The actual change or difference between groups (i.e. the “estimated treatment effect”)

• The 95% confidence interval for this estimate• The test used in the statistical analysis• Assurance that assumptions of analysis were met

– Acknowledge post hoc and subgroup analyses (avoid “data dredging”)

Discussion• Purpose: to explain the nature and importance of the

findings • Begin by summarizing the study and the main results.

– Interpret the results and suggest an explanation for them– Describe how the results compare with what else is known

about the problem; review the literature and put the results in context

– Suggest how the results might be generalized– Discuss the implication of the results – State the limitations of the study

• Distinguish between clinical and statistical significance

• In studies with low statistical power, do not mistake inconclusive results for negative results

• Absence of evidence is not Evidence of absence

References

• Purpose: to allow readers to verify authors’ claims and arguments

• Format according to the Uniform Requirements for Manuscripts Submitted to Biomedical Journals or to the journal's Guidelines for Authors

• Abbreviate journal titles according to National Library of Medicine guidelines

• Verify that the references are cited in the text and are numbered correctly

• Avoid unnecessary references

Of the following writing problems in manuscripts, which is most common?

Excessive abstraction Wordiness

Compressed thought Wrong words

Poor syntax Complexity

Needless repetition Unnecessary qualification

Poor flow of ideas

Of the following writing problems in manuscripts, which is most common?

1. Wordiness 6. Excessive abstraction

2. Poor flow of ideas 7. Wrong words

3. Poor syntax 8. Compressed thought

4. Needless repetition 9. Unnecessary qualification

5. Complexity

“Reader-Based” Writing

Write at the service of your reader:

Words: Less is more

Phrasing: Simpler is better

Editing: Rewrite for clarity

IMRD

Section Question Tense

Introduction Why? Present

Methods How? Past

Results Findings? Past

Discussion So what? Present

“85% of biomedical manuscripts eventually get

published”

www.icmje.org

• Review the “Uniform Requirements” published by International Committee of Medical Journal Editors

• Manuscript Preparation – useful section

Select the Most Appropriate Journal

• Consider the audience• Determine if your research matches journal’s

stated purpose• Evaluate the quality of the journal and probability

of acceptance

Journal Considerations

• Citation rates: metrics evaluate importance, but not necessarily quality– Immediacy index: citations/number of articles

published– Cited half-life: number of previous years accounting

for 50% of citations– Impact factor: Number of citations/number of

published articles (previous 2 years)

• Journals with higher immediacy indexes, shorter half-lives and higher impact factors are believed to be better journals

Understand and Follow Journal Guidelines

• Provide all requested information at first submission

• Follow all format guidelines, including page length

• Follow CONSORT guidelines for clinical trial reporting

• Follow the Uniform Requirements by icmje

Understand What Editors Want

• New

• True/hypothesis driven

• Important - “How will medicine be different as a result of your research?”

• Clearly reported

• Manuscripts prepared in accordance with the journal's Guidelines for Authors

Top Reasons for Rejection

1. Wrong journal - focus is not within scope of the journal

2. Redundant topic of research

3. Poorly written - poor grammar, style and syntax

4. Problem/hypothesis not adequately stated

5. Fatal flaws with study design - inadequate sample size, bias, insufficient detail

Top Reasons for Rejection

6. Over-interpretation of results

7. Incorrect statistical analysis

8. Faulty conclusions

9. Figure and tables confusing

10. Inappropriate review of literature

11.Failure to address reviewers’ suggestions

Summary

• Formulate research questions• Design studies carefully so they can

– Test hypotheses – Answer questions

• Publish the results so that– They enter the scientific body of

knowledge– Can be replicated– Can generate new research hypotheses

Summary

• Utilize the journal’s “Guidelines to Authors”

• Adhere to IMRD format, CONSORT statement and Uniform Requirements of ICMJE

• Incorporate all elements into the first submission– Careful editing and proofreading – Attention to submission requirements

CORC Review Criteria

• Credible: is the science accurate?

• Original: are the findings new?

• Relevant: does the study connect with current issues?

• Clear: can we understand the writing and graphics?

Read More

• www.clinicaltrials.gov

• www.consort-statement.org

• www.icmje.org

• Schold J: Design and Analysis of Clinical Trials in Transplantation – Principles and Pitfalls

AJT 2008; 8: 1779

Scientific Writing — easy when you know how

by J Peat, E Elliott, L Baur, and V Keena (Pp 312; £22.50)

BMJ Books, 2002.

What is your own strategy?

• Authorship – before starting• Methods (while performing the study)• Major findings in Tables and Figures• Results – text• Introduction• Discussion• Abstract• References

How much time do you need to do some work on the paper?

• A week?

• A day?

• Half a day?

• An hour?

• Half an hour?

Enjoy writing your paper !

• Writing a paper is creative, productive, artistic, inventive, inspiring, stimulating, exciting, reviving, …

• and sometimes quite fun

Professional Help:

San Fransisco Editwww.sfedit.net

Newsletters; very good advice

English language revision

- 29 USD/page

- done in one week