Pharmaceutical Medical Writing

1. Pharmaceutical Medical Writing Lorraine McMurdo, PhD Managing Director, Prescriptive Services Director, Pharmaceuticalethics.com lmcmurdo@preserv.co.uk Lorraine.McMurdo@pharmaceuticalethics.com

3. - GENERAL ASPECTS- CLINICAL STUDY DOCUMENTATION- MARKETING APPLICATIONS- JOURNALS/PUBLISHING

4. GENERAL ASPECTS

5. PHARMACEUTICAL WRITING The documents • Clinical trial protocols • Clinical trial reports • Journal manuscripts (original reports, reviews), chapters, books • Marketing applications (Common Technical Document) • Clinical Overview (Clinical Expert Report) • Integrated Efficacy Summary • Integrated Safety Summary

6. PHARMACEUTICAL WRITING General aspects (1) • Understand your readers, are they? • pharmaceutical employees, • academics • clinicians • therapeutic area specialists • native English speakers

7. PHARMACEUTICAL WRITING General aspects (2) • make a good first impression (meaningful title, honest abstract, useful table of contents) • use plain English and avoid jargon and acronyms • make documents that are user friendly (less is more, use tables and figures wisely) • be honest (p=0.09 is not ‘almost significant’) • be descriptive • be interpretative and extrapolate results to clinical practice

8. PHARMACEUTICAL WRITING Children need good schools if they are to learn properly. High-quality learning environments are a necessary precondition for facilitation and enhancement of the ongoing learning process.

9. PHARMACEUTICAL WRITING General aspects (3) Use plain English and avoid jargon and acronyms: “…while undertaking real time voice interaction with the patient...” “…the financial outlay for medication acquisition...” “…statistically significantly clinically superior..”

10. The power of brevity 15,800 1250 95 Lord’s US Declaration EU document Prayer of Independence vegetable prices (Number of Words)

11. GENERAL ASPECTS • Always consider your audience • Consult appropriate and relevant guidance • Be as clear and concise as possible

12. CLINICAL STUDY DOCUMENTATION

13. CLINICAL STUDY PROTOCOL Clinical study protocol • synopsis • background • study plan & procedures • measurement of variables • data management • planned statistical analysis * • study management • ethics • emergency procedures • references

14. How to get “clinically significant” randomised trials “Misinterpreting the results of trials can misinform future research and lead to suboptimal practice” • Clinical importance vs. statistical significance • Components of composite end points should be weighted • Hazards of subgroup analysis • (Kaul & Diamond, JACC 2010; 55:415-427)

15. In the accompanying JACC editorial… “…may stimulate vigorous healthy debate, their report’s underlying principles are well reasoned and should be required reading for healthcare providers and other professionals involved in organising or interpreting clinical trials.” (Stone & Pocock, JACC 2010; 55: 428-431.)

16. CLINICAL STUDY REPORT (CSR) The CSR is one of the most critical documents submitted as part of the Common Technical Document (CTD) in a Marketing Authorisation Application (MAA).

17. ICH E3 The content and format of a CSR is guided by the ICH Guideline E3 on structure and content of CSRs, which was approved in 1996.

18. CLINICAL STUDY REPORT Clinical study report • synopsis • introduction • objectives • patient demographics • efficacy results • safety results • discussion/conclusions • appendices (~20 volumes)

19. A word about abbreviated Clinical Study Reports… Some of the studies conducted during product development may ultimately not contribute to the evaluation of the effectiveness of a product for a specific indication. In these cases, abbreviated Clinical Study Reports are required to be submitted to the regulatory authorities.

20. STUDY DOCUMENTATION • A well designed study and solid protocol are key. • Give consideration to publication planning ASAP. • The Clinical Study Report is critical for the marketing application authorisation, i.e., in gaining regulatory approval for the Licence that you hope to get.

21. MARKETING APPLICATIONS

22. Summary of Product Characteristics (SmPC)

23. PHARMACEUTICAL WRITING Common Technical Document (CTD) • Submission requirements differed for EU, US and Japan • CTD (now eCTD) developed by EMEA, FDA and MHLW • The eCTD has five modules • Administrative Information and Prescribing Information • Common Technical Document Summaries • Quality • Nonclinical Study Reports • Clinical Study Reports

24. Module 1 Administrative and prescribing information (not harmonised) Module 2 Nonclinical overview Clinical overview Quality overall summary Clinical summary Nonclinical summary Module 3 Quality data Module 4 Nonclinical study reports Module 5 Clinical study reports MODULAR STRUCTURE OF COMMON TECHNICAL DOCUMENT (CTD)

25. BASIC STRUCTURE OF MODULE 5 OF THE CTD

26. PHARMACEUTICAL WRITING Marketing application: clinical section Clinical overview (Clinical expert report) • introduction (2 pages) • problem statement (3 pages) • clinical pharmacology (4 pages by a clinical pharmacologist) • clinical trials (global analysis of efficacy and of safety) (11 pages) • post-marketing experience (1 page) • conclusion (1-2 pages) • information about the clinical expert (0.25 pages)

27. MARKETING APPLICATIONS • The MAA granted will be based on the data contained in the Common Technical Document (eCTD). • The eCTD consists of 5 modules. Modules 2-5 are harmonised across countries. • Module 5 contains the Clinical Study Reports.

28. PUBLISHING/JOURNALS

29. PHARMACEUTICAL WRITING Journal manuscript (1) • Write it yourself but if you don’t have time, consider using a medical writer • Purpose • ethical (all research should be reported…even negative results) • pharmaceutical (prescribers, detailing) • personal (satisfaction, CV) Structure • title (use wisely) • abstract (consistency - cull from body of manuscript) • introduction (state hypotheses) • methods, results, discussion (be honest, be modest) • references • a response other than rejection is an acceptance

30. PHARMACEUTICAL WRITING Journal manuscript (2) • Authorship guidance – International Committee of Medical Journal Editors (www.icmje.org) • Authorship credit requires: • 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 • final approval of the version to be published • Every author should qualify for authorship and everyone who qualifies should be an author

31. PHARMACEUTICAL WRITING Journal manuscript (3) • Authorship responsibilities – International Committee of Medical Journal Editors (www.icmje.org) • Authors must specify their own and their sponsors roles in the research reported • Authors must take public responsibility for appropriate portions of the content • Authors must confirm that they had access to all data • Authors must confirm that they controlled decision to publish • Authors must confirm that they prepared their report independently and freely

33. GPP2 GUIDELINES (British Medical Journal 2009; 339:b4330)

34. GPP2 GUIDELINES • Aim to stamp out “ghostwriting.” • Developed in collaboration with the European Medical Writers Association (EMWA). • Conduct and communication of medical research, including that sponsored by pharma, continues to be criticised. • Declaration of Helsinki 2008 places accuracy and completeness among the primary ethical obligations of individuals communicating medical research. • GPP2 guidelines designed to ensure that publication of clinical research results by the pharmaceutical industry is done to the highest ethical standards. (British Medical Journal 2009; 339:b4330)

35. GPP2 checklist for articles & presentations (British Medical Journal 2009; 339:b4330)

36. Roche accused again of withholding Tamiflu data

37. Roche and Tamiflu • Two years after Roche said it would release key Tamiflu data for independent scrutiny, the safety and effectiveness of the drug remains uncertain, according to a report by the Cochrane Collaboration. • The Report states that Roche’s refusal to provide full access to all its data leaves critical questions about how well the drug works, unresolved. • A BMJ investigation has been published to coincide with Cochrane’s report, and raises serious concerns about access to drug data, the use of ghost-writers in drug trials, and the drug approval process. • The BMJ says this situation must be resolved as Tamiflu has become the mainstay of influenza treatment in the UK, and has also made it onto the WHO’s list of essential medicines.

38. Roche and Tamiflu • The Cochrane researchers set out to test Roche’s claim that Tamiflu prevented complications and reduced the number of people needing hospital treatment. But their investigation was hampered by Roche’s refusal to provide all of its trial data for analysis. • The team obtained some clinical study reports from the European Medicines Agency, but found inconsistencies with published reports and possible under-reporting of side effects. • The BMJ noted that Roche had admitted that some of the published papers had been ghost-written and that “different regulators took different approaches to the data submitted to them, leading to conflicting messages about its effectiveness.”

39. Fiona Godlee, BMJ editor-in-chief said she hoped that the EMA will indeed keep its promise about publishing reports, “but we are still a long way away from having a full trial history for all drugs in clinical use. Public safety and the proper use of public money demands that we should stop at nothing less.”

40. PUBLISHING/JOURNALS • Companies must publish trial results. • Write the article in-house if you have the time and expertise. • Consider using a medical writer or Communications Agency – be transparent at all times. • Consult guidance – GPP2.

41. - GENERAL ASPECTS- CLINICAL STUDY DOCUMENTATION- MARKETING APPLICATIONS- JOURNALS/PUBLISHING

42. “Don’t write merely to be understood. Write so that you cannot possibly be misunderstood.” (Robert Louis Stephenson, 1850-1894)