Writing a research manuscript and getting it published

1. Writing a research manuscript and getting it published Phil Halloran American Journal of Transplantation Wednesday, Feb 10 2010

2. Learning objectives: to understand • (Digression: The four types of questions) • Research project design and analysis • Preparing a manuscript: AIMRD • How editors make decisions

3. The four types of questions How a speaker should approach questions form the audience

4. There are only four types of questions • You know the answer • You do not know the answer • You do not understand the question • The questioner has another agenda (e.g. he hates your supervisor)

5. Answering type 1 questions:you know the answer (basic paragraph) • Sentence 1: the answer to the question • Sentence 2: evidence for the statement • Sentence 3: evidence against the statement • Why you believe the arguments are wrong • Sentence 4: advantages or consequences

6. Answering type 2 questionsi.e. you do not know the answer • Sentence 1: “I do not know the answer” • Sentence 2: (optional) “but person X may know” • Resist the impulse to pretend you know • or to obscure the fact that you do not know

7. Answering questions of type 3you do not understand the question • Sentence 1: Please repeat the question • If they repeat and you still do not understand • Sentence 2: I believe what you are saying is this…and answer the question you believe they are asking

8. Answering type 4 questionsthe hostile questioner with an agenda • Be patient during the question • Keep eye contact, then: • Sentence 1 is “I think we have to agree to disagree – maybe we can discuss this after the session”

9. Learning objectives: to understand • (Digression: The four types of questions) • Research project design and analysis • Preparing a manuscript: AIMRD • How editors make decisions

10. Research Essentials • Hypothesis generation and testing • Trial/experimental design • Statistical analysis plan • Trial registration • Publishing

11. 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 The Importance of Publishing The peer review process is an essential part of science

12. 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 • 1987: Introduction of structured abstracts • CONSORT Statement for reporting randomized trials adopted by JAMA

13. http://www.consort-statement.org/

14. CONSORT • Consolidated Standards of Reporting Trials • A detailed website that includes translations in many major languages including Chinese

15. 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 including explanation of any interim analyses and stopping rules

16. 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

17. 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

18. 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

19. Clinical Trial Registration:Why Register? • Increases transparency and strength/validity of scientific database • Increases public awareness and access to trials • Assigns trial identifier

20. 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 Clinical Trial Registration:www.clinicaltrials.gov

22. Learning objectives: to understand • (Digression: The four types of questions) • Research project design and analysis • Preparing a manuscript: AIMRD • How editors make decisions

23. Types of “original studies”: research transplant papers • Model systems • Intervention trials: must be registered • Laboratory investigations of population • Outcome analysis • Registry analysis • Case series • Case report Remember to document: Clinical trials CONSORT institutional review board patient consent

24. What are your controls?How will they limit your conclusions? Sick versus well Sick versus sick (+ self organized)

25. Strength in multiple dimensions • Clinical • Laboratory • Histopathology • Molecular phenotype • Outcomes

26. Other formats • Meta-analysis • Systematic reviews • Minireviews • Reviews • Guidelines • Meeting reports • Consensus statements • CPCs and didactic papers

27. Writing the paper • Prepare the data: figures and tables • Decide on your “story”: story line • Write methods, results • Results: describe but do not “discuss” • do not spin or sell the results • avoid adjectives and adverbs: “extraordinary”, “dramatically decreased” • understatement is often impressive to the reader • Introduction: keep it short, review relevant literature • Discussion: restate highlights then discuss

28. J D Watson and F H C CrickMolecular Structure Of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid J.D. Watson, and F.H.C. Crick Nature 171: 137, 1953 “We wish to suggest a structure for the salt of deoxyribose nucleicacid (D.N.A.). This structure has novel features which are ofconsiderable biological interest.”

29. Rules for writing EnglishGeorge Orwell Politics and the English Language 1946 • Never use a metaphor, simile, or other figure of speech which you are used to seeing in print. • Never use a long word where a short one will do. • If it is possible to cut a word out, always cut it out. • Never use the passive where you can use the active. • Never use a foreign phrase, a scientific word, or a jargon word if you can think of an everyday English equivalent. • Break any of these rules sooner than say anything outright barbarous. • With scientific writing, we break rule #5 for precision and accuracy, but we also keep it in mind

30. Proofread and have it read by others • A critical re-review is essential • spelling and grammar • technical issues: e.g. are tables and figures numbered properly and mentioned in the text • Ask for and listen to criticism • Careful manuscript preparation aids your probability of acceptance: credibility

31. The 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) • Attempt to incorporate the following elements: • Patients • Intervention • Comparator • Outcome • Design • Setting

32. 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

33. Abstract • Purpose: to help readers decide whether to read the full article: Second most important part • Types: • Descriptive: state what was done and what was found • Structured: follow headings used by the journal • Word limit - usually 200-250; 250 words for structured abstracts • Must stand alone • Provide 3 to 6 key words

34. 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

35. 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

36. 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

37. 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

38. Results • Present the results of the study • 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 mining”) • Do you need validation? Yes if you “trained” on the data

39. 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 • Avoid “trends” unless they undermine your conclusions

40. The discussion • Paragraph 1 reviews results in perspective • do not duplicate the introduction or the abstract • Paragraph 2 -6: every paragraph is an argument • starts with an assertion: like answering a “type 1” question • echo points in introduction BUT do not repeat introduction • sentence 1 asserts your argument or belief • sentence 2 may state why you believe this • later sentences may present differing points of view and why you disagree with them • last sentence may state the consequences or importance of the point you are making

41. 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 (but consider who is refereeing!)

42. “Reader-Based” Writing • Write at the service of your reader: • Words: Less is more; take out adjectives and adverbs e.g. “dramatic” • Phrasing: Simpler is better • Editing: Rewrite for clarity

43. IMRD

44. 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 • Review “Uniform Requirements” published by International Committee of Medical Journal Editors (www.icmje.org)

46. 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

47. 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

48. Conclusions • 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

49. Conclusions • Utilize the journal’s “Guidelines to Authors” • Adhere to IMRD format • Incorporate all elements into the first submission • Careful editing and proofreading • Attention to submission requirements

50. Learning objectives: to understand • (Digression: The four types of questions) • Research project design and analysis • Preparing a manuscript: AIMRD • How editors make decisions