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Medical Writing 02 December 2015
Medical Writing
02 December 2015
Today’s Programme
16:00-16:10 Welcome 16:10-16.20 Introduction to Medical Writing Carsten Roepstorff, Director, Science & Medical Writing, Larix A/S
16:20-16:50 Medical Writing of Regulatory Documents Jeff Craven, Principal Medical Writer, Larix A/S
16:50-17:20 Break/Networking 17:20-17:50 Publication Medical Writing Angela Stocks, Principal Medical Writer, Larix A/S
17:50-18:00 Additional Questions/Wrap-up
Medical Writing Medical Writing
The 3rd Meeting in a Seminar Series on Data Handling and Reporting
Data Management Statistics
Publication Medical Writing
Regulatory Medical Writing
Take Home Messages
Publication Medical Writing
Publication Medical Writing is a regulated discipline with
many requirements to adhere to
Regulatory Medical Writing
Regulatory Medical Writing
involves teamwork with important input
needed from all of you
Take Home Messages
Larix Full service Contract Research Organisation Founded in Denmark in 2001 Present in Sweden since February 2015 Present in Norway and Finland since July 2015 70 employees
Larix Provides a full range of services to the biotech, pharmaceutical and medical device industry within:
Clinical Operations
Regulatory Services
Pharmacovigilance
Data Management
Statistics
Medical Writing
Clinical Pharmacology
GCP and Vendor Audits
System Validation
Data Monitoring Committee
European larch [Larix decidua]
Larix Science & Medical Writing We are 7 Medical Writers A total of 97 years of Clinical Development experience Hereof, 58 years of Medical Writing experience
We do Regulatory Medical Writing Publication Medical Writing
What is Medical Writing?
The activity of writing clinical and medical scientific documentation by someone who is a specialised writer (and has excellent scientific skills) Evolved as a field in pharmaceutical industry because
increasing complexity and requirements of clinical development procedures have demanded well-written, well-structured and standards-compliant documentation
Medical Writing in a Clinical Study
Planning Conduct Reporting
Clinical Study Flow
IMP Dossier
Investigator’s Brochure
Protocol
Patient Information
Clinical Study Report
Abstract
Poster
Manuscript
Important Skills as a Medical Writer
Excellent writing skills
Strong scientific
skills
Attention to detail
Project manage-
ment skills
Great inter-
personal skills
The Typical Background
PhD
MSc
BSc Other
Source: DMWN survey, 2011
Other
Medicine Pharmacology
Veterinary/ Dentistry
Biotechnology
Biology (human/cell/ molecular)
Larix Science & Medical Writing: - 1 DVM, 5 PhD’s, 1 MSc - Human Nutrition, Medicine, Biology, Clinical Pharmacology, Human Biology, Biomedical Chemistry, Veterinary Pharmacology, Biochemistry and Microbiology, Human Physiology, Veterinary Medicine
Experience with other Clinical Development Functions
Newly graduated
Source: DMWN survey, 2011
Academia research
Pharma research
Trial Manager
Regulatory Affairs Marketing
Other
Larix Science & Medical Writing: - Previous experience as CRA, Trial Manager, Pharma Research Scientist, Data Manager, Safety Surveillance Advisor, Medical Advisor, Clinical Pharmacologist
What is Medical Writing? The activity of writing clinical and medical scientific
documentation by someone who is a specialised writer (and has excellent scientific skills) Evolved as a field in pharmaceutical industry because
increasing complexity and requirements of clinical development procedures have demanded well-written, well-structured and standards-compliant documentation
Publication Medical Writing is a regulated discipline with
many requirements to adhere to
Regulatory Medical Writing
involves teamwork with important input
needed from all of you
Regulatory Medical Writing
Typical Regulatory Writer Types of Regulatory Documents Clinical Study Report (CSR) CSR Contents Disclosure
The Regulatory Writer
Excellent writing skills
Strong scientific
skills
Attention to detail
Project manage-
ment skills
Great inter-
personal skills
Regulatory and
statistical knowledge
‘Thick skinned’
Regulatory Documents
Phase 1 Phase 2 Phase 3 Marketing Authorisation
Post Marketing
Protocol Clinical Study Report
Investigator’s Brochure
Investigational Medicinal Product Dossier
Risk Management Plans PSUR DSUR
Patient Information/Patient Informed Consent
Value Dossier
Clinical Summaries
Briefing Book
Clinical Overview
Clinical Investigational Plans
Clinical Investigational Reports
Clinical Evaluation Reports
Clinical Literature Reviews
PMA Annual Reports
IND/BLA Annual Reports
The Clinical Study Report (CSR) - An integrated presentation of the study
Format based on ICH guideline E3 from 1995
Clinical Study Report
Protocol
Statistical Analysis
Study Results
Study Documentation
Summarised Subject Data
Producing a CSR
Add text for results
driven sections
Add text for
protocol driven
sections
Design tables, figures
and listings
Review and
approval Publishing
CSR Process – Protocol Sections
Data Manager
Statistician
Trial Manager
Add text for protocol driven
sections
Monitor
CSR Process – Result Sections
Safety
Statistician
Trial Manager
Add text for results driven
sections
Medical
CSR - Table of Content
CSR Table of Contents (2)
CSR Table of Contents (3)
CSR Table of Contents (4)
CSR Table of Contents (5)
CSR Appendices
CSR Appendices (2)
CSR Complexity
Approximately how many individual documents are compiled to form a complete CSR for a large phase 3 trial?
50 500 20000 500
Impact of Investigator on CSR
Safety of subjects Subject inclusion Quality of subject efficacy data Adverse event reporting Protocol deviations/amendments Co-ordinating (signatory) investigator also involved in reviewing/approving the CSR
Impact of Monitors on CSR
Quality of subject efficacy data Adverse event reporting Protocol deviations Drug supply/accountability
Public Disclosure Clinicaltrials.gov
• Most well known database • US sponsors required to post summary results of
trials of approved products • EU sponsors also post summary results due to
requirements for journal publication EUDRACT
• Requirement to post results of all studies conducted in at least 1 EU country (functional June 2014)
Public Disclosure (2)
Clinical Trial Regulation • Sponsor required to submit a technical summary of
results from clinical trials and ”…a summary that is understandable to laypersons”
• CSR available 30 days after approval (for trials supporting a marketing application)
Many companies have committed to making CSRs available on public websites (as ”redacted” documents)
What is Redaction?
Removal of: Subject sensitive information
• Subject identifiers Direct identifiers (age, sex, subject number) Indirect identifiers (laboratory measurements, medication)
• Verbatim text
Company sensitive data
Example of redaction
Subject 100013 (1 event): This event concerned a xx-year-old male and was reported as hospitalisation due to moderate nausea (CTCAE grade 2). The subject was treated with WONDERDRUG on 05-Aug-2014. On 10-Aug-2014, the subject was admitted to hospital due to nausea and vomiting since 07-Aug-2014. The subject was treated with Medrol 100 mg once daily from 31-Jul-2014 to 20-Aug-2014, with 80 mg once daily from 21 to 27-Aug-2014, and 64 mg once daily from 27-Aug-2014. On 18-Aug-2014, the subject was considered recovered, he did no longer have any symptoms of nausea and vomiting but stayed in hospital as the social situation at home was unsustainable. On 28-Aug-2014, the subject was discharged to a hospice. The subject was discontinued from the study on 02-Sep-2014 due to progressive disease. The event was assessed as not related to study product.
Example of redaction
Subject 100013 (1 event): This event concerned a xx-year-old male and was reported as hospitalisation due to moderate nausea (CTCAE grade 2). The subject was treated with WONDERDRUG on 05-Aug-2014. On 10-Aug-2014, the subject was admitted to hospital due to nausea and vomiting since 07-Aug-2014. The subject was treated with Medrol 100 mg once daily from 31-Jul-2014 to 20-Aug-2014, with 80 mg once daily from 21 to 27-Aug-2014, and 64 mg once daily from 27-Aug-2014. On 18-Aug-2014, the subject was considered recovered, he did no longer have any symptoms of nausea and vomiting but stayed in hospital as the social situation at home was unsustainable. On 28-Aug-2014, the subject was discharged to a hospice. The subject was discontinued from the study on 02-Sep-2014 due to progressive disease. The event was assessed as not related to study product.
Summary
Regulatory Medical Writers are involved in many documents before and after a clinical trial Regulatory Medical Writing involves teamwork with important input needed from many sources
What is Medical Writing? The activity of writing clinical and medical scientific
documentation by someone who is a specialised writer (and has excellent scientific skills) Evolved as a field in pharmaceutical industry because
increasing complexity and requirements of clinical development procedures have demanded well-written, well-structured and standards-compliant documentation
Publication Medical Writing is a regulated discipline with
many requirements to adhere to
Regulatory Medical Writing
involves teamwork with important input
needed from all of you
Publication Medical Writing
Why publish? Unethical practices Guidelines and position statements Steps involved in writing publications Why use a professional medical writer?
‘Thick skinned’ Diplomatic
Regulatory and
statistical knowledge
Publication ethics and guidelines
The Publication Writer
Excellent writing skills
Strong scientific
skills
Attention to detail
Project manage-
ment skills
Great inter-
personal skills
Succinct writing
Types of Publications
Journal articles / manuscripts (research articles, case reports, review articles) Abstracts Posters & oral presentations for scientific meetings and conferences
Why Publish? (1)
WMA Declaration of Helsinki: www.wma.net (Adopted in 1964) • October 2013:
• Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard to the publication and dissemination of the results of research. Researchers have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports. All parties should adhere to accepted guidelines for ethical reporting. Negative and inconclusive as well as positive results must be published or otherwise made publicly available. Sources of funding, institutional affiliations and conflicts of interest must be declared in the publication. Reports of research not in accordance with the principles of this Declaration should not be accepted for publication.
Why Publish? (2)
Why Publish? (2)
The innovative pharmaceutical industry is committed to the transparency of clinical trials that
are sponsored by its member companies.
Why Publish? (3)
What? • All industry-sponsored clinical trials should be considered for
publication irrespective of whether the results of the sponsors’ medicine(s) are positive or negative.
When? • Submission of manuscripts should ideally occur within 12 months and no
more than 18 months after approval of the product concerned or the decision to discontinue the trial. In the case of a product which is already marketed, submission should ideally be within 12 months of the completion of the trial and not more than 18 months after that date.
Where? • It should be the intention to submit clinical trial results for publication as
manuscripts in peer-reviewed journals.
Why Publish? (3)
What? • All industry-sponsored clinical trials should be considered for
publication irrespective of whether the results of the sponsors’ medicine(s) are positive or negative.
When? • Submission of manuscripts should ideally occur within 12 months and no
more than 18 months after approval of the product concerned or the decision to discontinue the trial. In the case of a product which is already marketed, submission should ideally be within 12 months of the completion of the trial and not more than 18 months after that date.
Where? • It should be the intention to submit clinical trial results for publication as
manuscripts in peer-reviewed journals.
ClinicalTrials.gov is designed to complement, not replace, journal
publication
Intense Media Attention
Unethical Practices (1) Study not reported Study selectively/incompletely reported
• Misleading study results/conclusions being used by patients and healthcare providers
Guest (‘honorary’) authorship • Individuals who are listed as an author despite not qualifying for
authorship Ghost writing
• When an individual (e.g., medical writer) assists in the preparation of a manuscript but is not acknowledged
Ghost authorship • Individuals who qualify as author but are not listed as author
Unethical Practices (2) Lack of transparency
• Who funded/sponsored the work? • Did authors have any conflicts of interest (disclosures) that
could potentially bias the conclusions of the manuscript? Plagiarism
• To use another person's idea or a part of their work and pretend that it is your own
Duplicate (redundant) publications • When the same results are
published twice Breaking patient confidentiality
Guidelines & Position Statements
Many organizations have produced guidelines • Editors, publishers, industry, medical writers, etc. • Much consistency among these different guidelines
What are Reporting Guidelines? Reporting guidelines are statements that provide advice on
how to report research methods and findings. They focus on encouraging authors to provide clear and transparent reporting of the facts relating to the research carried out. Most widely recognized guidelines reflect consensus opinion
of groups of experts in a particular field, including research methodologists and journal editors Medical journals, including BMJ, JAMA, Lancet, and NEJM
often require compliance to specific reporting guidelines Collection of tools and guidelines e.g. CONSORT
(Consolidated Standards of Reporting Trials) can be found on the
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GPP3 Guidelines
Good Publication Practice for communicating company sponsored medical research: the GPP3 guidelines
• Guidelines developed by the International Society for Medical Publication Professionals
• Guidelines covering: • Roles and responsibilities Written agreement with authors is recommended Authors’ responsibility regarding authorship
• Contributorship and acknowledgments • Role of professional medical writers Working with authors As authors
New
Ann Intern Med. 2015;163(6):461-464
GPP3 Guidelines (2) What Is New in GPP3? Guidance on updated ICMJE 2013 authorship criteria Guidance on common issues about authorship Guidance and improved clarity on author payment and reimbursement Additional clarity on what constitutes ghost or guest authorship Expanded information on the role and benefit of professional medical writers Guidance for appropriate data sharing Overall simplification of language and format with a new guiding principles section and quick reference tables addressing guidance on authorship criteria and common authorship issues
GPP3 = Good Publication Practice 3 guideline; ICMJE = International Committee of Medical Journal Editors.
Steps in Writing Publications (1)
Manuscript group kick-off
meeting
Manuscript outline
Manuscript draft development
Approval of manuscript by
authors
Submission of manuscript to
journal
Feedback from journal
Approval of revision by
authors
Resubmission of manuscript to
journal
Published manuscript!!
New
Steps in Writing Publications (2)
External guidelines
(CONSORT, GPP-3, ICMJE, EMWA, etc.)
Final publication QC processes
Manuscript preparation SOPs
Table and figure preparation
Journal instructions
to authors
Example manuscript
Literature search
Language and Grammar Skills
Present information in a clear manner and at a level of understanding appropriate to the target audience Use of grammatically correct language Simple short sentences Logical flow of ideas Avoid use of highly complex technical jargon “Strike out any phrase you consider particularly clever” (Diabetologia 2012; What does an Editor look for?)
Why use a professional medical writer?
Reasons for Journal Rejections
Why use a professional medical writer?
Bad language and poor formatting should not get in the way of good
science
Reasons for Journal Rejections
Summary
Medical writing is both a science and an art Medical writers enjoy writing!
Thank you for your attention
Questions?
Larix A/S Lyskær 8B
DK-2730 Herlev www.larixcro.com +45 70 27 22 21
Carsten Roepstorff Director, Science & Medical Writing
Jeff Craven Principal Medical Writer
Angela Stocks Principal Medical Writer
