What's in your kit? The Medical Translator's Guide to Navigating Clinical Trials and Investigational Documentation

Erin M. Lyons

What’s in Your Kit?

The Medical Translator’s Guide to Navigating Clinical Trials and Investigational Documentation

Webinar Quiz: Question 1

What is the “gold standard” for collecting evidence about the performance of a medical device?

A. Case seriesB. Randomized controlled trial C. Observational studyD. Integrative study

What’s in Your Kit? The Medical Translator’s Guide to Navigating Clinical Trials and Investigational Documentation

Webinar Quiz: Question 2What is a “Notified Body” in European medical device regulation?

A. An entity of a national government in the EU entitled to grant approval

B. A private organization accredited by the government entitled to grant approval

C. The manufacturer labeling the product with the CE marking

D. A subcommittee of the Directorates-General of Health and Consumers


Webinar Quiz: Question 3Physicien (FR) means:

A. Physical therapistB. PhysicianC. PhysiologistD. Physicist


Webinar Quiz: Question 4Which of these does not belong?

A. Desinfectado (ES)B. Disinfected (EN)C. Désinfecté (FR)D. Desinfektiert (DE)


Webinar Quiz: Question 5Documentation necessary to enroll a patient in a trial:

A. ProtocolB. Case report form C. Informed consent form D. Investigator’s brochure


Webinar snapshot

• To summarize the clinical trial pipeline• To address terminological challenges• To contextualize electronic documentation

and technological developments for translators

• To identify dedicated linguistic resources


Clinical Trials: The Basics


What is a clinical trial?

• Biomedical or health-related research studies that follow a pre-defined protocol

• One of the final stages in the long process of drug research and discovery

• Required for marketing authorizationfrom regulatory authorities


Types of clinical trials

• Treatment trials• Prevention trials• Diagnostic trials• Screening trials• Quality of life/Supportive care trials


Clinical trial phases


Global: Not a should but a must


• To strengthen intellectual property• To decrease time-to-market (millions in

potential revenue)• To capitalize on seasonal reversal in

Southern Hemisphere (allergies, flu, etc.)

So many trials… so few patients


Poll 1: Foreign participation


Poll 1: Foreign participation


What percentage of subjects participating in clinical trials supporting marketing applications for drugs were enrolled at foreign sites?

87% (foreign subjects in clinical trials on biologics)21% 57%% 10%

Source: “Challenges to FDA's Ability to Monitor and Inspect Foreign Clinical Trials,” Dept. of Health and Human Services Office of Inspector General, June 2010.http://oig.hhs.gov/oei/reports/oei-01-08-00510.pdf

Growth in overseas trials

• Over 40% of US-regulated trials are conducted oversees

• In the next two to three years, up to 65% of FDA-regulated trials will be conducted abroad

• “Pharmerging” markets: Brazil, China, Russia, India


Clinical trials around the world


International trials in the news


International standards

• ICH Good Clinical Practice GuidelinesHow trials should be conducted, roles and responsibilities of sponsors, investigators, and monitors

• Declaration of HelsinkiEthical principles on human experimentation; cornerstone document for human research ethics


Available in multiple languages (including

glossaries)

Terminology Challenges


Medical usage and abusage

• Default to literal/equivalence translations may be inappropriate and/or deadly

• Medical writing uses a specific style and jargon that can be foreign to linguists

• Interlinguistic shifts in terminology


Poll 2: Localization


Localization: Regulatory

• Institutional Review Board (IRB)Group of scientists, doctors, clergy, and consumers at each participating health facility who evaluate and approve the trial design and protocol.

Ethics Committee (EC)Comité de protection de personnes (CPP)Research Ethics Board (REB)


Regional divergences

• Regional differences in the regulatory/approval process

• Locale-specific terminology• Variations in healthcare systems• Readability index for target population

(consent forms, patient information, etc.)


Geographic usage


Term France Belgium Switzerland Canada

Recommandations 9 2

Lignes directrices 1 2

Guides 1 1

Source: “Répertoire des lignes directrices de pratique médicale et tables rondes consensus francophones, ” http://www.chu-rouen.fr/ssf/recomfr.html, p. 1-6.

Observation: Canada tends to use the verb

recommander, which makes it impossible to use

recommandations as the subject of the verb

Terminology shifts• English has a relatively large vocabulary,

creating language shifts during translation


Source Translation Comment

Aches and pains Rigidez (ES) 2 words do not exist in Spanish for “aches” and “pains”

Cytomegalovirus (CMV) (--) (EL)

No abbreviation available in Greek, use full term

Magnetic ResonanceImaging (MRI)

Segulómun (MRI) (IS)

Interchangeable use of full Icelandic term and borrowed EN term

Faux amis – False friends• Cognates and faux amis can be deadly in

a clinical context


Source Faux amis translation Correct translation

(RU) Angina (EN) Tonsillitis

Auricle (FR) Auricle (EN) Atrium

After (DE) After (EN) Anus

Carbunco (ES) Carbuncle (EN) Anthrax

Aspirazione (IT) Aspiration (EN) Suction

Cases, Patients, Subjects, Controls• Patient

A person receiving medical care• Case

An instance of a disorder or disease• Subject

A human/animal with a particular characteristic• Control (subject)

A human/animal that does not have that particular characteristic


Efficacy vs. Effectiveness

• EfficacyDemonstrates a benefit under design or research conditions (research setting)

• EffectivenessDemonstrates a benefit under conditions of actual use (day-to-day clinical practice)

Example: Pulse oximeters have demonstrated their efficacy, but clinical studies are being performed to demonstrate their effectiveness


Prevalence vs. Incidence

• PrevalenceProportion of new events in a population or group of patients

• IncidenceThe rate of development of new events in a population or group of patients per unit of time


Divergent medical terminology


Condition Cause of condition

English French

Natural sleep Sleep Sommeil

Condition in which the patient responds to suggestion

Hypnotism (non-drug-related maneuvers)

Hypnosis HypnoseSynonyms:État hypnotiqueÉtat hypnoïde

Narcoanalysis, Narcosynthesis (Low doses of anesthesia)

Subnarcosis

Hypnosis

SubnarcoseSynonyms:Narcose liminaireHypnose* (not rec.)

Artificial sleep, Loss of consciousnessfrom anesthesia (deep sleep)

Drugs (somniferous drugs, anesthesia)

NarcosisPharmacologicalhypnosisSleep* (not rec.)Hypnosis* (not rec.)

Narcose

Hypnose* (not rec.)

Usage: For or against vaccines?Vaccin antigrippal, vaccin grippal, vaccin contre la grippe (FR)

Vacuna antigripal, vacuna gripal, vacuna contra la gripe (ES)

Flu vaccine (EN)


Getting it Right: Term Mapping


Remember:

• Know your limitations• Expand your toolbox• Different jobs require different approaches• Don’t make assumptions: check and

double check


Electronic Documentation and Technology


Wave of the future

• It is only a matter of time before all source data is captured in electronic format

Eliminates unnecessary duplication of dataReduces the opportunity for transcription errorsPromotes real-time entry of source data during visitsEnsures the accuracy and completeness of data

• Until then… we have the eCRF!


What is an eCRF?

• A vehicle to assemble data from electronic- and paper-based systems

• Captures and organizes diverse data to satisfy the study protocol

• Enables the data to be systematically reviewed and analyzed by investigators and other authorized parties


Poll 3: eCRFs


Poll 3: eCRFs


True or False: eCRFs will replace ALLsource documentation (progress notes, lab results, X-rays, etc.)?

TrueFalse

Assembling data using an eCRF


What does this mean for translators?• Translation and transfer of medical data to

a harmonized format• Translation of eCRF and QA prompts• Translation of site-specific reporting forms

for automated import into eCRF• Translation of local proprietary input

systems (not global-ready)


Translators and QA

• Back-translation is an essential benchmarking tool

• Development of glossaries and controlled input language for languages/locales

• Stakeholder in regulatory review/audits• “Clean” data review


Back-translation & in-country review• Informed consent forms, patient-reported

outcomes Back-translation confirms that content and readability are unaffected

• Marketing materials and labelingIn-country review guarantees appropriateness for specific markets


Controlled language and CAT

• Upstream internationalization and localization of embedded systems

• Mapping to classifications and standard glossaries (Systematized Nomenclature of Medicine – Clinical Terms, SNOMED CT)

• Downstream translation and retooling for specific markets


A virtual collaborative environment

• Translators link data managers and local clinicians via central database regardless of language or location

• Multilingual IVRS integration• Real-time roll-out of protocol changes• Translators on call for out-of-box

adverse events


Content repurposing

• Translators adapt and repurpose content (media syndication, Web publishing, etc.)

• Trans-adaptation and push-button publishing

• Consolidation and review in regulated fields


A double-edged sword?

• Accelerated timelines and more commodity-driven process

• TMs/glossaries are not “intelligent” tools• Technological learning curve

for translators• Costly add-on tools?


Resources


General Clinical Trial Resources• EU Clinical Trials Register

Primary registry of WHO’s International Clinical Trials Registry Platformwww.clinicaltrialsregister.eu

• European Union Drug Regulating Authorities Pharmacovigilance (EudraVigilance)EMA scientific guidelineswww.Eudravigilance.emea.europe.eu

• US Clinical Trials DatabaseUS registry of clinical trials in a harmonized formatwww.clinicaltrials.gov

• WHO International Clinical Trials Registry Platform (ICTRP)Online, multilingual international clinical trials registrywww.who.it/ictrp/en


Clinical Trial Terminology• Johns Hopkins Medicine IRB Guidelines

Glossaries, templates, and guidelines on the clinical trial processwww.hopkinsmedicine.org/institutional_review_board/guidelines_policies/guidelines/

• The Medical Dictionary for Regulatory Activities (MedDRA) Reference for describing adverse eventswww.meddramsso.com

• Stanford Clinical Trials DictionaryGlossary of terms specific to clinical researchhumansubjects.stanford.edu/new/docs/glossary_definitions/definitions.pdf

• Stanford Lay Language DictionaryGlossary of medical terms and corresponding lay terms and definitionshumansubjects.stanford.edu/new/docs/glossary_definitions/lay_language.pdf


Informed Consent• Coded ICF Lexicon

Term or phrase with alternatives to medical terminologywww.calgb.org/Public/meetings/presentations/2009/summer_group/cra_cont_ed/04c_lexicon_062009.pdf

• Stanford ICF templates and subject bill of rightsWith templates in English, Chinese, Farsi, Japanese, Korean, Russian, Spanish, and Vietnamesehumansubjects.stanford.edu/new/resources/consent/short_form_consent_process.html


Medical Terminology• MediLexicon

Medical abbreviations and dictionary (English with some French, German, and Spanish translations)www.medilexicon.com

• Medline Plus DictionaryNational Library of Medicine Dictionarywww.nlm.nih.gov/medlineplus/mplusdictionary.html

• RxListOnline drug index, including side effects, interactions, etc.www.rxlist.com

• EMAFrequently used non-standard abbreviationshttp://www.emea.europa.eu/htms/human/qrd/docs/listnonstandard.pdf


Essential Print Resources


• Davis, Neil M. Medical Abbreviations: 15,000 Conveniences at the Expense of Communications and Safety, 10th ed. Huntington Valley, PA: Davis Associates, 2001.

• Donaldson, Ross. Tarascon Medical Translation Pocketbook, 1 Mul. ed. Boston: Jones and Bartlett: 2009.

• Maxwell, Robert. Maxwell Quick Medical Reference, 5th ed. Maxwell Pub. Co., 2006.

• Sabatine, Marc S. Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine , 3rd ed. Philadelphia: Wolters Kluwer, 2008.

• Stanaszek, Mary J. The Inverted Medical Dictionary. Lancaster, PA: Technomic, 1991.

Tool Box For the Medical Translator

• One of the most comprehensive lists of resources for novice or experienced medical translatorshttp://www.groupetraduction.ca/documents/ToolBox.pdf


Questions?


Documents

What's in your kit? The Medical Translator's Guide to Navigating Clinical Trials and Investigational Documentation