1. Clinical Writing for Interventional Cardiologists

2. What you will learn - hopefully! Introduction General principles for clinical writing Specific techniques Practical session: critical review of a published article Writing the Title and the Abstract Bibliographic search and writing the Introduction Principles of statistics and writing the Methods Practical session: writing the Abstract Writing the Results Writing the Discussion Writing Tables and preparing Figures Principles of peer-review Principles of grant writing/regulatory submission Clinical writing at a glance Conclusions and take home messages

3. What you will learn - hopefully! Introduction General principles for clinical writing Specific techniques Practical session: critical review of a published article Writing the Title and the Abstract Bibliographic search and writing the Introduction Principles of statistics and writing the Methods Practical session: writing the Abstract Writing the Results Writing the Discussion Writing Tables and preparing Figures Principles of peer-review Principles of grant writing/regulatory submission Clinical writing at a glance Conclusions and take home messages

4. Introductory remarks Clinical writing is just like PCI

5. Introductory remarks Clinical writing is just like PCI: nobody is accomplished at the beginning, but all remarkably improve with practice

6. Introductory remarks What are our goals?

7. Introductory remarks What are our goals? –to provide you a set of general methods, specific tips and tricks, and real-life scenarios –to figure out what, when, why, and how to write a clinical paper

8. Questions?

9. What you will learn - hopefully! Introduction General principles for clinical writing Specific techniques Practical session: critical review of a published article Writing the Title and the Abstract Bibliographic search and writing the Introduction Principles of statistics and writing the Methods Practical session: writing the Abstract Writing the Results Writing the Discussion Writing Tables and preparing Figures Principles of peer-review Principles of grant writing/regulatory submission Clinical writing at a glance Conclusions and take home messages

10. What you will learn General principles for clinical writing –choice of English –reasons for writing clinical papers –gestational time for clinical papers –hierarchy of clinical literature and evidence –practical flowchart for clinical writing

11. Choice of English

12. Why is this presentation in English? Choice of English

13. Why is this presentation in English? Questa presentazione è stata preparata in lingua inglese per permettervi di familiarizzarvi con la terminologia e gli approcci alla scrittura in lingua inglese, e anche perché così il relatore ha potuto risparmiare tempo e parole, ed essere più chiaro. (single sentence, 39 words) This presentation was prepared in English to enable you to familiarize with English terms and approaches. Moreover, the speaker could thus save time and words, being also clearer. (two sentences, 28 words) Choice of English

14. What you will learn General principles for clinical writing –choice of English –reasons for writing clinical papers –gestational time for clinical papers –hierarchy of clinical literature and evidence –useful concepts –practical flowchart for clinical writing

15. Clinical research writing Is writing a clinical research paper easy?

16. Remember Grossman’s words I have not found…writing one bit easier today than it was 30 years ago. I still have to work at it very hard and make many revisions, with a rare exception… because the saying of Francis Bacon has always been deeply impressed in my mind..”Writing [maketh an] exact man.” Morton Grossman (>400 scientific papers, 134 editorials, and 71 books or book chapters)

17. Paraphrasing Groucho… The more you write, the better writer you will become… …and if I can write in ENGLISH, most of you can!

18. But life is too short Is the paper worth writing? –Have similar findings been reported? –Is there a need for another report? –Are your findings more convincing? Is the paper important? –Apply the “so-what” test

19. Reasons for writing a paper A clinician can write a paper for several reasons: -divertissement -build up the CV -self-advertising -increase collective knowledge

20. Other reasons No publication, no project  Make information available for others No publication, no promotion  Yardstick of productivity No publication, no funding  What have you done for me lately?

21. Other reasons I would urge you to write, not because it is a good thing, not because it is nice to see your name in print,… but rather because you will really get to know a field only if you contribute to it Mahoney MJ, Psychology of the Scientist 1979

22. Disclaimer This talk will not help you if you have nothing to write about: 1.Ability to ask a good question 2.Commitment to career development 3.Willingness to or experience in research 4.Ability to protect your time

23. Who gets the credit? In science, the credit goes to the man who convinces the world, not to the man to whom the idea first occurs. ─ Sir Francis Darwin

24. Advice: keep enjoying writing Smith et al, BMJ 2003

25. Advice: bring the draft wherever it suits you

26. Advice: maintain a global view as well as a…

27. …focused, structured and analytic approach Which color for her eyes? Is she a she or a he? What landscape should I paint? Who cares about this painting? In a few years nobody will see it! Am I in love with her?

28. What you will learn General principles for clinical writing –choice of English –reasons for writing clinical papers –gestational time for clinical papers –hierarchy of clinical literature and evidence –useful concepts –practical flowchart for clinical writing

29. Gestational period for a clinical trial paper START STUDIES/ EXPERIMENTS WRITE AND SUBMIT REWRITE AND RESUBMIT WAIT PUBLISHED! 4-24 months 2-4 months 14-44 Months! PROTOCOL/IRB 2-4 months BEST GUESS

30. Time to publication More realistic time from submission to publication projections in the WWW era: Letters to the Editor4-12 weeks Editorials3-6 months Reviews6-12 months Case reports6-12 months Non-RCT clinical studies6-18 months RCTs6-18 months Ground-breaking RCTs<6 months

31. Setting goals First author papers in major journals First author papers in secondary journals Total papers –Non-first author papers –Secondary journals –Book chapters or review papers (AVOID [?])

32. Tracking goals Every 3-6 months, tabulate: –Published papers in past year (P pub ) –Number of papers under review (P rev ) –Number of papers in preparation (P prep )

33. Probable annual production (PAP) PAP raw = P pub + P rev + P prep 3

34. Barriers to goals Extrinsic - Major clinical/teaching/research responsibilities (R) - Major committee assignments (C) - Personnel disputes (Pers) - Grants (Gr) Intrinsic

35. Adjusted Probable Annual Production (PAP adj ) PAP adj = PAP raw – 2 * (Gr n + Pers n ) – (R + C)

36. Internal censors – Fears of failure Perfectionism Procrastination Intrinsic causes of writing problems

37. Censors “Watchers at the Gate” - Internal censors - Internal critics Induce bad feelings about writing Undermine ability to generate ideas

38. Assuming the voices of parents, teachers, and other authority figures, he whispers and sometimes shouts that our writing is bad… He edits words and thoughts before we have a chance to put them on paper, and thus creates a blank page panic. Censors When you hear him, the internal critic speaks in a shrill tone, rational, often pessimistic, alerts only to the dangers of the world around us, and therefore to the shortcomings in our work.

39. Intrinsic blocks to writing Inability to start writing: - “First, there is the difficulty of writing at all” D. Brande Becoming a Writer - Perfectionism, self-consciousness, procrastination

40. How to increase and sustain productivity Time management Stimulus control Contingency management Limit and deadline setting

41. How to increase and sustain productivity Work: Daily 30 minutes to one hour Do not pay attention to structure, grammar, spelling Jump from project to project

42. Spontaneous writing “You can’t think and hit at the same time” Y. Berra Learn to write: –Without feeling “ready” –Without feeling fully in control –Without awaiting inspiration “Learning to write at a gallop leaves one’s internal critics behind” V. Woolf Once under way, writing builds its own momentum

43. Best time to write Morning Afternoon Evening Night Pick a time and protect it!!!

44. Inability to finish writing Multiple revisions Multiple analyses “Each time I think I am finished, I see there is a lot more to do” Similar roots as inability to start (perfectionism) Different people Lack of insight

45. What you will learn General principles for clinical writing –choice of English –reasons for writing clinical papers –gestational time for clinical papers –hierarchy of clinical literature and evidence –useful concepts –practical flowchart for clinical writing

46. Which manuscript?

47. Before beginning writing, you need to choose the manuscript type/design Which manuscript?

48. Choosing a manuscript type Manuscript type Abstract for scientific meeting Letter to the Editor Editorial Book chapter Qualitative review Systematic review Case reports or Images Case series Non-RCT study RCT

49. Choosing a manuscript type Manuscript type Effort Abstract for scientific meeting ± Letter to the Editor ± Editorial + Book chapter + Qualitative review + Systematic review ++ Case reports or Images ± Case series + Non-RCT study ++ RCT+++

50. Choosing a manuscript type Manuscript type EffortReward Abstract for scientific meeting ± ± Letter to the Editor ± ± Editorial + + Book chapter + + Qualitative review + + Systematic review ++ ++ Case reports or Images ± ± Case series + + Non-RCT study ++ ++ RCT+++ +++

51. Choosing a manuscript type Manuscript type EffortReward Abstract for scientific meeting ± ± Letter to the Editor ± ± Editorial + + Book chapter + + Qualitative review + + Systematic review ++ ++ Case reports or Images ± ± Case series + + Non-RCT study ++ ++ RCT +++ +++

52. Levels of articles Primary: Peer Reviewed Secondary: Not peer reviewed Primary Secondary

53. Levels of peer-reviewed articles Primary: original research Secondary: review articles Tertiary: textbooks, summaries Primary Secondary Tertiary

54. Parallel hierarchy of CV research Biondi-Zoccai et al, Ital Heart J 2003 Qualitative reviews Systematic reviews Meta-analyses from individual studies Meta-analyses from individual patient data Case reports and series Observational studies Observational controlled studies Randomized controlled trials Multicenter randomized controlled trials

55. What about evidence-based medicine? Excerpt from a 1990 leaflet for internal medicine resident at McMaster University (Hamilton, Canada): “…goal of evidence-based medicine is to be aware of the evidence on which one’s practice is based, the soundness of the evidence, and the strength of inference the evidence permits. The strategy employed requires a clear delineation of the relevant question(s); a thorough search of the literature relating to questions; a critical appraisal of the evidence, and its applicability to the clinical situation; and a balanced application of the conclusions to the clinical problem.” Guyatt and Rennie, Users’ guide to the medical literature, 2002

56. Evidence-based medicine (EBM) Definition: The coscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence-based medicine requires integration of individual clinical expertise and patient preferences with the best available external clinical evidence from systematic search. Guyatt and Rennie, Users’ guide to the medical literature, 2002

57. Rebuttal to critics of EBM Evidence alone is never sufficient to make a clinical decision: decision makers must always trade the benefits and risks, inconvenience, and costs associated with alternative management strategies, and in doing so consider the patient’s values! Guyatt and Rennie, Users’ guide to the medical literature, 2002

58. EBM hierarchy of evidence 1.N of 1 randomized controlled trial 2.Systematic reviews of randomized trials 3.Single randomized trial 4.Systematic review of observational studies addressing patient-important outcomes 5.Single observational study addressing patient-important outcomes 6.Physiologic studies (eg blood pressure, cardiac output, exercise capacity, bone density, and so forth) 7.Unsystematic clinical observations Guyatt and Rennie, Users’ guide to the medical literature, 2002

59. Basic science study Kwon et al, J Clin Invest 1998

60. Joner et al, JACC 2008 Preclinical study

61. Image in medicine Sheiban et al, J Cardiovasc Med 2007

62. McFadden et al, Lancet 2004 Case report(s)

63. Cross-sectional study Herrington et al, Circulation 2004

64. Case-control study Fujii et al, JACC 2005

65. Cohort study (registry) Lee et al, EuroInterv 2007

66. Cohort study (registry)

67. Non-randomized controlled study Ong et al, JACC 2005

68. Cross-over study Bansch et al, Circulation 2004

69. Fajadet et al, Circulation 2006 A pivotal randomized trial

70. A pragmatic randomized trial Galloe et al, JAMA 2008

71. Editorial Camenzind, NEJM 2006

72. Qualitative review Romagnoli et al, JACC Int 2008

73. Qualitative review Melikian et al, Heart 2008

74. Systematic review (without meta-analysis) Kip et al, JACC 2008

75. Study level meta-analysis Agostoni et al, JACC 2004

76. Individual patient level meta-analysis ATC, BMJ 2002

77. Kastrati et al, NEJM 2007 Another individual patient level meta-analysis

78. Your choice of type/design The optimal type/design depends on your skills, findings, message and audience But remember your ultimate goal…

79. Ultimate goal of research: appraisal of causation

80. What you will learn General principles for clinical writing –choice of English –reasons for writing clinical papers –gestational time for clinical papers –hierarchy of clinical literature and evidence –useful concepts –practical flowchart for clinical writing

81. Precision and accuracy Random and systematic (ie bias) errors Internal and external (ie generalizability) validity Type I (alpha) and type II (beta) errors Sample size and statistical power Some other pivotal (and useful) concepts

82. Accuracy and precision Accuracy measures the distance from the true value distance Precision measures the spead in the measurements spread true value measurement

83. Accuracy and precision

84. example Accuracy and precision Schultz et al, Am Heart J 2004

85. example Schultz et al, Am Heart J 2004 Accuracy and precision

86. Random and systematic errors Thus Precision expresses the extent of RANDOM ERROR Accuracy expresses the extent of SYSTEMATIC ERROR (ie bias)

87. Bias Bias is a systematic DEVIATION from the TRUTH - in itself it cannot be ever recognized - there is a need for external gold standard and/or permanent surveillance

88. An incomplete list of bias Simplest classification: 1. Selection bias 2. Information bias · Selection bias · Information bias · Confounders · Observation bias · Investigator’s bias (enthusiasm bias) · Patient’s background bias · Distribution of pathological changes bias · Selection bias · Small sample size bias · Reporting bias · Referral bias · Variation bias · Recall bias · Statistical bias · Selection bias · Confounding · Intervention bias · Measurement or information · Interpretation bias · Publication bias · Subject selection/sampling bias Sackett, J Chronic Dis 1979

89. Validity Internal validity entails both PRECISION and ACCURACY (ie does a study provide a truthful answer to the research question?) External validity expresses the extent to which the results can be applied to other contexts and settings. It corresponds to the distinction between SAMPLE and POPULATION)

90. Rothwell, Lancet 2005 Validity

91. Alpha and type I error Whenever I perform a test, there is thus a risk of a FALSE POSITIVE result, ie REJECTING A TRUE null hypothesis This error is called type I, is measured as alpha and its unit is the p value The lower the p value, the lower the risk of falling into a type I error (ie the HIGHER the SPECIFICITY of the test)

92. Type I error is like a MIRAGE Because I see something that does NOT exist Alpha and type I error

93. Beta and type II error Whenever I perform a test, there is also a risk of a FALSE NEGATIVE result, ie NOT REJECTING A FALSE null hypothesis This error is called type II, is measured as beta, and its unit is a probability The complementary of beta is called power The lower the beta, the lower the risk of missing a true difference (ie the HIGHER the SENSITIVITY of the test)

94. Type II error is like being BLIND Because I do NOT see something that exists Beta and type II error

95. Summary of errors Experimental study H 0 acceptedH 0 rejected Truth H 0 true Type I error H 0 false Type II error

96. Power and sample size Whenever designing a study or analyzing a dataset, it is important to estimate the sample size or the power of the comparison SAMPLE SIZE Setting a specific alpha and a specific beta, you calculate the necessary sample size given the average inter-group difference and its variation POWER Given a specific sample size and alpha, in light of the calculated average inter-group difference and its variation, you obtain an estimate of the power (ie 1-beta)

97. What you will learn General principles for clinical writing –choice of English –reasons for writing clinical papers –gestational time for clinical papers –hierarchy of clinical literature and evidence –useful concepts –practical flowchart for clinical writing

98. Flowchart for paper drafting

99. 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Flowchart for paper drafting

100. 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Flowchart for paper drafting Choose your title at the very beginning, even before starting collecting data!

101. 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Flowchart for paper drafting Begin drafting your abstract as soon as possible, leaving “…” where detailed results will come after data collection

102. 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Flowchart for paper drafting Write and close the Introduction even before beginning data collection. This will save you time and you will not have to go back to this tedious section any longer

103. 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Flowchart for paper drafting Methods should, obviously, be completed as soon as possible, as only those procedures that you have thought out will be followed during the study conduct

104. 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Flowchart for paper drafting Results can also be preliminarily drafted before study completion, leaving “…” where detailed data will come out

105. 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Flowchart for paper drafting The Conclusion is the main message of your work. Figure out ASAP your true bottom line, and then work on the rest of the paper accordingly

106. 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Flowchart for paper drafting The Discussion will follow easily. I usually spend no more than a couple of days of work on it (leaving a few traps for reviewers)

107. Flowchart for paper drafting 1.Title 2.Abstract 3.Introduction 4.Methods 5.Results 6.Conclusion 7.Discussion Quite often, results modify your overall view of the topic and lead you to revisions of the whole paper

108. Questions?

109. Take home messages

110. 1.Know your subject well 2.Know who your readers are and what they want 3.Know how to use the tools of written expression 4.Read a lot 5.Follow the journal’s rules Take home messages

111. 6. Schedule time for writing 7. Wear one hat at a time a. Student b. Clinician c. Planner d. Creator e. Proofreader f. Editor

112. For further slides on these topics please feel free to visit the metcardio.org website: http://www.metcardio.org/slides.html http://www.metcardio.org/slides.html