Presentation working on clinical trials

Working on Clinical Trials – Getting started

Very few clinical trials are conducted only in one country; many are available in a variety of different sites in different places, so the translation and linguistic adaptation for different target cultures and languages becomes more important – but it’s not easy to find professionals who specialize in this specific field. With my presentation I hope to provide an overview of what makes the linguistic work on clinical trials so special, what kind of texts and target audiences there are and what knowledge linguists need to acquire in order to efficiently work in this area. This is especially interesting for translators who already specialize in the medical field, but also for linguists interested in legal, business, marketing and related field who would like to add an interesting niche with high demand to their specialization.
The presentation aims to be an introduction to the characteristics and requirements of the linguistic work on texts related to clinical trials. It not only wants to give a brief overview of how clinical trials work and who the stakeholders are, but also underline the skills and knowledge set linguists who would like to further specialize in this field should acquire. It also provides them with the necessary resources to get them started. The main topics are as follows:
• Introduction to clinical trials (what are they; how do they work; who is implied)
• Types of documents used in clinical trials (medical [specialist facing/ patient facing]; legal; marketing, etc.)
• Types of audiences (doctors/investigators/healthcare providers; patients/ other laymen such as healthy subjects/ partners/ legal representatives/ parents, etc.; ECs; CROs…)
• What skills do linguists need to work in this field?
• How to acquire that knowledge?
- Where to find glossaries/ templates/ further information
- MOOCs to take to get you started
- Books you should have read
- Other handy resources

1. Working on Clinical Trials Introduction to clinical trials (what are they; how do they work; who is implied) Types of documents used in clinical trials (medical [specialist facing/ patient facing]; legal; marketing, etc.) Types of audiences (doctors/investigators/healthcare providers; patients/ other laymen such as healthy subjects/ partners/ legal representatives/ parents, etc.; ECs; CROs…) What skills do linguists need to work in this field? How to acquire that knowledge? Where to find glossaries/ templates/ further information MOOCs to take to get you started Books and articles you should have read Other handy resources

2. Introduction to Clinical Trials http://web.chem.ucla.edu/~harding/IGOC/C/clinical_trial.html Legal Basics: clinical trials have to comply with strict regulations Declaration of Helsinki International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) > Good Clinical Practice (GCP) national/ EU guidelines (AMG, EU Clinical Trials Directive) national/ EU regulatory authorities (BfArM, PEI, EMA)

3. Introduction to Clinical Trials http://web.chem.ucla.edu/~harding/IGOC/C/clinical_trial.html Important for linguists: different conditions and medical specializations different types of documentation many texts have to be handed in for approval > have to adapt to certain specifications

4. Introduction to Clinical Trials Prospective biomedical or behavioral research study of human subjects Designed to answer specific questions about biomedical or behavioral interventions e.g.: vaccines, drugs, treatments, devices, new ways of using known drugs, treatments, or devices Used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective Include behavioral human subjects research involving an intervention to modify behavior increasing the use of an intervention willingness to pay for an intervention, etc. Clinical trials of experimental drug, treatment, device or behavioral intervention may proceed through four phases Phase I First stage testing a new intervention in humans 10 - 30 people identify tolerable dose information on drug metabolism, excretion, toxicity not necessarily controlled Phase II 30 - 100 people preliminary information on efficacy, additional information on safety and side effects Phase III 100 + people efficacy and safety controlled and normally randomized Phase IV conducted after the intervention has been marketed monitor effectiveness of the approved intervention in the general population collect information about any adverse effects http://web.chem.ucla.edu/~harding/IGOC/C/clinical_trial.html

5. Types of documents used in Clinical Trials According to Good Clinical Practice (GCP), all information and processes of clinical trials must be recorded and stored so that they can be correctly reported, interpreted and authenticated. Many different types of documents are created, processed and filed in the process of clinical studies. As per ICH GCP E6 Section 8 , essential documents are those which: (…) individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, sponsor and monitor with the standards of Good Clinical Practice and with all applicable regulatory requirements. Other important uses and objectives of essential documents are: • correct management of the trial in question by investigators, sponsors and monitors; • audits; • inspections by regulatory authorities. There are mainly three stages in which essential documents are generated and handled, namely: 1 Before the start of the clinical phase of the trial 2 During the clinical phase of the trial 3 After the clinical phase of the trial All documentation needs to be described and it must be defined whether they are stored in the files of either the study site (investigator or institution), the sponsor, or both. See the European Commission’s  Detailed Guidance on the Content of a Trial Master File and Archiving for more information on Trial Master Files. In some cases, documents may be combined if all essential parts are still clear and can be easily identified. Very few clinical trials are conducted only in one country; many are available in a variety of different sites in different places, so the translation and linguistic adaptation for different target cultures and languages becomes more important. However, requirements as to which types of documents need to be translated differ from country to country. Whereas in some states all documents need to be available in the local language, others assume that specialist-facing text will be understood in English, and only texts that are not directly addressing the study staff involved in the trial need to be translated , such as: • Packaging and labeling • Patient diaries • Patient information sheets • Informed consent forms • Patient questionnaires • Patient-reported outcomes

6. Types of documents used in Clinical Trials Before the start of the clinical phase of the trial Authorization/approval/notifications by regulatory authorities (if applicable) Certificate of Analysis of Investigational Products shipped Composition of Institutional Review Board (IRB) and Independent Ethics Committee (IEC) Curriculum Vitae and other relevant information/documents regarding the qualification of the investigators involved in the trial Decoding procedures for blinded trials Documentation from IRB (only applicable in the US) and/or IEC providing approval/favorable opinion on: • Protocol and its amendments (if applicable) • Case Report Form (CRF) (if applicable) • ICF(s) • Other written information for subjects • Advertisement for subject recruitment (if applicable) • Subject compensation (if applicable) • Any other documents that require approval/a favorable opinion Financial aspects of the trial Information given to trial subjects, such as: • Informed Consent Form (ICF). All applicable translations also have to be filed • Other written information • Marketing material for subject recruitment (if applicable) Insurance statement Instructions for handling of investigational product and trial-related materials Investigator’s brochure Master randomization list Medical/laboratory/technical procedures and/or tests: • Certification, or • Accreditation, or • Established quality control and/or external quality assessment, or • Other validation (if applicable) Normal values for medical/laboratory/technical procedures and/or tests included in the protocol Pre-trial monitoring report Sample of labels for investigational product containers Shipping records for investigational products and trial-related materials Signed agreement between involved parties, such as: • Investigator/institution and sponsor • Investigator/institution and Contract Research Organization (CRO) • Sponsor and CRO • Investigator/institution and authorities. Signed protocol and amendments (if applicable); sample CRF Trial initiation monitoring report

7. Types of documents used in Clinical Trials During the clinical phase of the trial Any revisions to: • Protocol/amendments and CRF • Informed consent form • Other written information provided to subjects • Advertisement for subject recruitment Certificate of analysis for new batches of investigational products Curriculum Vitae for new investigators Dated and documented approval/favorable opinion of IRB/IEC of the following: • Protocol amendments • Revisions of: • Informed consent form • Other written information to be provided to the subject • Advertisement for subject recruitment • Any other documents given approval/favorable opinion • Continuing review of trial (if applicable) Documentation of CRF corrections Documentation of investigational products and trial-related materials shipment Interim or annual reports to IRB/IEC and authority or authorities Investigational products accountability at the site Investigator’s brochure updates Monitoring visit reports Notification by originating investigator to sponsor of serious adverse events and related reports Notification by sponsor and/or investigator (where applicable) to the regulatory authority or authorities and IRB/IEC of unexpected serious adverse drug reactions as well as other safety information Notification by sponsor to investigators of safety information Record of retained body fluids/tissue samples (if applicable) Regulatory authorities authorizations/approvals/notifications where required for protocol amendments and other documents Relevant communications other than site visits • Letters • Meeting notes • Notes of telephone calls Signature sheet Signed informed consent forms Signed, dated and completed CRFs Source documents Subject enrollment log Subject identification code list Subject screening log Updates regarding medical/laboratory/technical procedures/tests in the protocol Updates of medical/laboratory/technical procedures/tests: • Certification, or • Accreditation, or • Established quality control and/or external quality assessment, or • Other validation (where required)

8. Types of documents used in Clinical Trials After the clinical phase of the trial Audit certificate (if applicable) Clinical study report Completed subject identification code list Documentation of investigational product destruction Final report by investigator to IRB/IEC where required, and to the regulatory authority or authorities (if applicable) Final trial close-out monitoring report Investigational product accountability at site Treatment allocation and decoding documentationTypes of audiences (doctors/investigators/healthcare providers; patients/ other laymen such as healthy subjects/ partners/ legal representatives/ parents, etc.; ECs; CROs…)

9. Types of audiences Doctors/ investigators/ healthcare providers Patients Other laymen such as healthy subjects/ partners/ legal representatives/ parents, etc. ECs ; CROs

10. What skills do linguists need to work in this field? Basic knowledge about the functioning of clinical trials Specific terminology Adapt texts for different audiences

11. What skills do linguists need to work in this field? Laymen texts: patients or voluntary participants family/spouse/guardian avoid anglicisms / latinisms if they are not widely understood style and expression should be easy to understand no long and complicated syntax Influenza > Flu Placebo > Placebo Screening > Voruntersuchung depends on language (Romance languages + English > layman term often = Latin term; other Germanic languages normally don’t use the Latin term in every day language) Example solutions: omit specialist term The patient has a fever. give explanation + specialist term in brackets The patient has a fever (pyrexia). give specialist term and explain in brackets The patient has pyrexia (fever).

12. What skills do linguists need to work in this field? > Double check with client/ style guides that may have been provided as this might depend on ECs/ Regulatory Authorities (local entities) > might even be handled differently for different languages in the same study. > You can also check instructions directly on the websites of the Ethics Committee in question

13. How to acquire that knowledge? Where to find glossaries/ templates/ further information MOOCs to take to get you started Books and articles you should have read Other handy resources

14. Where to find glossaries / templates/ further information https://clinicaltrials.gov/ct2/info/glossary

15. Where to find glossaries / templates/ further information https://medlineplus.gov/mplusdictionary.html

16. Where to find glossaries / templates/ further information https://prsinfo.clinicaltrials.gov/definitions.html

17. Where to find glossaries / templates/ further information NCI Drug Dictionary https://www.cancer.gov/publications/dictionaries/cancer-drug/ Thieme https://www.thieme.de/viamedici/klinik-infos-zur-klinik-1516/a/abkuerzungen-3968.htm Beckers Abkürzungslexikon http://www.medizinische-abkuerzungen.de/ Univadis https://www.univadis.com/references Dornblüth Klinisches Lexikon http://www.textlog.de/9609.html DocCheck Flexikon http://translate.google.de/translate?js=n&prev=_t&hl=de&ie=UTF-8&layout=2&eotf=1&sl=de&tl=en&u=http://flexikon.doccheck.com&act=url MediLexicon http://www.medilexicon.com/ Medizin Lexikon http://www.gesundheit.de/lexika/medizin-lexikon Dorlands https://www.dorlands.com/wsearch.jsp Cosnautas http://www.cosnautas.com/catalogo Tremédica http://www.tremedica.org/panacea/IndiceGeneral/n44_tradyterm-EVazquezDelArbol.pdf Lista de Glosarios en español http://pablomuguerza.com/minicoleccion-de-glosarios-y-buscadores-de-acronimos-y-siglas/

18. Where to find glossaries/ templates / further information http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000134.jsp&mid=WC0b01ac0580022c59

19. Where to find glossaries/ templates / further information http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000134.jsp&mid=WC0b01ac0580022c59

20. Where to find glossaries/ templates/ further information https://www.ecpdwebinars.co.uk/downloads/ema-templates-and-eu-terminology-for-medical-translators-the-basics-2/

21. Where to find glossaries/ templates / further information Ethic Committees http://www.swissethics.ch/templates.html http://ethikkommission.blaek.de/studien/amg-studien http://ethikkommission.meduniwien.ac.at/service/patienteninformation/ http://www.medunigraz.at/ethikkommission/Graz/Richtl/frame.htm https://www.medunigraz.at/ethikkommission/Forum/Download/piev.htm https://ethikkommission.charite.de/antraege/ http://www.ak-med-ethik-komm.de/index.php?lang=de http://www.uni-regensburg.de/medizin/ethikkommission/weitere-informationen/patienteninformation/index.html

22. MOOCs to take to get you started Johns Hopkins University: Design and Interpretation of Clinical Trials https://www.coursera.org/learn/clinical-trials Introduction to Systematic Review and Meta-Analysis https://www.coursera.org/learn/systematic-review National Drug Abuse Treatment Clinical Trials Network: Good Clinical Practice https://gcp.nihtraining.com/ National Institutes of Health: Clinical Research Training https://crt.nihtraining.com/ University of California, San Diego: Drug Discovery https://www.coursera.org/learn/drug-discovery Drug Development https://www.coursera.org/learn/drug-development Drug Commercialization https://www.coursera.org/learn/drug-commercialization University of Cape Town: Understanding Clinical Research: Behind the Statistics https://www.coursera.org/learn/clinical-research University of Minnesota: Healthcare Marketplace https://www.coursera.org/learn/healthcare-marketplace University of Pennsylvania: Vital Signs: Understanding What the Body Is Telling Us https://www.coursera.org/learn/vital-signs University of Pittsburgh: Clinical Terminology for International and U.S. Students https://www.coursera.org/learn/clinical-terminology Vanderbilt University: Data Management for Clinical Research https://www.coursera.org/learn/clinical-data-management

23. Books and articles Daniela Penn: Ein Überblick über klinische Studien und das Übersetzen von Studiendokumenten http://www.bdue-fachverlag.de/fachverlag/detail_book/110 Shayne Cox Gad: Clinical Trials handbookhttps://books.google.es/books?id=d8GxG0d9rpgC&pg=PA118&redir_esc=y#v=onepage&q&f=false S. D.  MathiasS . K.  FiferD . L.  Patrick:Rapid translation of quality of life measures for international clinical trials: avoiding errors in the minimalist approach http://link.springer.com/article/10.1007/BF00435392 Dictionaries for your language combination

24. Other handy resources NIH Toolkit for Clinical Researchers https://www.nidcr.nih.gov/research/toolkit/#startup2 UBC Webinars http://www.ubc.com/library/archived-webinars USC Information about Clinical Trials https://research.usc.edu/clinical-trials-at-usc/ NCI's Clinical Trials Programs and Initiatives https://www.cancer.gov/research/areas/clinical-trials My blog http://www.henter.co/documents-used-in-clinical-trials/ http://www.henter.co/specialization-courses-for-medical-translators-and-interpreters/