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

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)

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

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 IFirst stage testing a new intervention in humans

10 - 30 people

identify tolerable dose

information on drug metabolism, excretion, toxicity

not necessarily controlled

Phase II30 - 100 people

preliminary information on efficacy, additional information on safety and side effects

Phase III100 + 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

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 trial2 During the clinical phase of the trial3 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

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 shippedComposition 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 trialDecoding procedures for blinded trialsDocumentation 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 trialInformation 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 brochureMaster randomization listMedical/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 reportSample of labels for investigational product containersShipping records for investigational products and trial-

related materialsSigned 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

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 productsCurriculum Vitae for new investigatorsDated 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 correctionsDocumentation of investigational products and trial-related

materials shipmentInterim or annual reports to IRB/IEC and authority or authoritiesInvestigational products accountability at the siteInvestigator’s brochure updatesMonitoring visit reportsNotification 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 informationRecord of retained body fluids/tissue samples (if applicable)Regulatory authorities authorizations/approvals/notifications where

required for protocol amendments and other documentsRelevant communications other than site visits

• Letters• Meeting notes• Notes of telephone calls

Signature sheetSigned informed consent formsSigned, dated and completed CRFsSource documentsSubject enrollment logSubject identification code listSubject screening logUpdates regarding medical/laboratory/technical procedures/tests

in the protocolUpdates of medical/laboratory/technical procedures/tests:

• Certification, or• Accreditation, or• Established quality control and/or external quality assessment, or• Other validation (where required)

Types of documents used in Clinical Trials

After the clinical phase of the trial

Audit certificate (if applicable)Clinical study reportCompleted subject identification code listDocumentation of investigational product destructionFinal report by investigator to IRB/IEC where required, and to the regulatory authority or authorities (if applicable)Final trial close-out monitoring reportInvestigational product accountability at siteTreatment allocation and decoding documentationTypes of audiences (doctors/investigators/healthcare providers; patients/ other laymen such as healthy subjects/ partners/ legal representatives/ parents, etc.; ECs; CROs…)

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?•Basic knowledge about the functioning of clinical trials

•Specific terminology•Adapt texts for different audiences

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).

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

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

Where to find glossaries/ templates/ further

information

https://clinicaltrials.gov/ct2/info/glossary

Where to find glossaries/ templates/ further

information

https://medlineplus.gov/mplusdictionary.html

Where to find glossaries/ templates/ further

information

https://prsinfo.clinicaltrials.gov/definitions.html

Where to find glossaries/ templates/ further

informationNCI 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 Abkürzungslexikonhttp://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/

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

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

Where to find glossaries/ templates/ further

information

https://www.ecpdwebinars.co.uk/downloads/ema-templates-and-eu-terminology-for-medical-translators-the-basics-2/

Where to find glossaries/ templates/ further

informationEthic 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

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

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

Other handy resources

NIH Toolkit for Clinical Researchers• https://www.nidcr.nih.gov/research/toolkit/#start

up2

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-t

rials

My blog• http://www.henter.co/documents-used-in-clinical

-trials/• http://www.henter.co/specialization-courses-for-

medical-translators-and-interpreters/