SAFETY ISSUES RESULTING FROM POOR TRANSLATION OF CLINICAL TRIAL by 0wAQ9jf

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									SAFETY ISSUES RESULTING FROM POOR
TRANSLATION OF CLINICAL TRIAL
DOCUMENTS

When Science Meets Regulation and Culture


Dorit Eldar, M.D., Medical Director
BQT Biomedical Translations, Petach Tikva, Israel

Yehudith Wexler , Chairperson
BioForum Group, Ness-Zionna, Israel


Acknowledgements: Stanley G. Garbus, M.D., Garbus Consulting
TABLE OF CONTENTS



INTRODUCTION
PART 1: Poor Translation of Clinical Trial Documents –
        Safety Risks to the Participant
PART 2: Poor Translation of Clinical Trial Documents –
        Safety Risks to others
PART 3: Common problems of poor translation
PART 4: Understand the cost of poor translation
PART 5: Fundamental Skills Needed for High Quality
        Translation of Clinical Trials Documents




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    INTRODUCTION




Use of poor translation results in poor language in general
   Art




                                      Beetles?


      3
    INTRODUCTION – cont.




   Literature, cinema, poetry…
   The press
                                      ?‫השטחים הכבושים / המשוחררים‬   



Use of poor language affects us in many levels, including sub-conscious
  levels




      4
    INTRODUCTION – cont.




   Medicine



                 ‫החיים והמוות ביד הלשון‬

                     Body = ?‫גוף? גופה‬




     5
       INTRODUCTION – cont.


                 Medicine - cont
                      Effective communication between patient and provider of medical
                       care is critical to the delivery of safe, high-quality care.
                      Patients have to understand the questions they are asked and the
                       information that is given to them.
                      Studies have shown:
                       Patients with low language proficiency are at increased risk of
                       experiencing an AE. The issue has been studied in countries with a
                       high proportion of new immigrants whose knowledge of English is
                       limited – US, Canada, Australia (1, 2). Lately such increased risk is
                       present also in the European Community due to greater patient
                       mobility (3).

1.   Johnstone MJ, Kanitsaki O.
     Culture, language and patient safety: making the link. Int J Qual Health Care 2006; 18: 385-388
2.   Divi C, et al.
     Language proficiency and adverse events in US hospitals: a pilot study. Int J Qual Health Care 2007; 19: 60-67
3.   Groene O, et al.
     Quality requirements for cross border care in Europe: a qualitative study of patients', professionals' and health
     care financiers' views. Qual Saf Health Care 2009; 18: Suppl i.15-i. 21




         6
INTRODUCTION – cont.

    Medicine - cont

Hence the safety of patients participating in a clinical trial may be
   jeopardized because of their poor language proficiency and also
   because of faulty translation of trial related documents.
         Any inconsistency between the original text and the translated
          one may lead to lack of comprehension or to
          misunderstanding, bad decisions and dangerous activities
         Inaccuracy may be critical
         Use of high language may lead to misunderstanding,
          withdrawal of the subject's consent, irrelevant concerns and
          unnecessary fears
         Omission of text – may be dangerous




 7
  INTRODUCTION – cont.

                     Documents written by of for
                           the Sponsor




                   Translator




 Documents to Local Readers:           Documents written by local parties:
candidates, patients, investigators,             physicians,
 study staff, ECs, authorities, etc.         authorities, EC, etc.


  Sometimes the client’s expectations from the translated
   document cannot be reached by the market since the
  combination of professional translation and biomedical
               knowledge is not common
   8
 INTRODUCTION – cont.


 Every document has a purpose


ONE fundamental purpose:

To inform
            (the participant – ICF
            the attending physician – Form 11
            the study team – patient diary
            the investigator – investigator’s brochure…)




  9
 INTRODUCTION – cont.
 The purpose determines the target reader.
 Thus,
 Every document has its target reader


 Examples:


Informed Consent Form –         the candidate / volunteer
Protocol synopsis –    the investigators and study staff
IB –                                    the investigators
Safety reports –                         the safety board
EC correspondence –                investigator/ sponsor
Patient diary –              the patient / and study staff
Patient emergency card –                          anyone

Letters -                  the attending physician, etc.



   10
INTRODUCTION – cont.


Each target reader has its characteristics


Examples:

The candidate / patient / participant / volunteer: “the layman”, lacks
medical background, has an 8th grade reading level, sometimes is
sick, sometimes suffers from side effects, is under a lot of stress,
surrounded by advice givers

The sponsor, investigators and members of safety boards:
professionals, extensive medical background, specifically in the
study’s subject, busy, high academic reading level

The study staff - medical background, busy, academic reading level



 11
 INTRODUCTION – cont.

 The information, vocabulary and style of the
 document should be adjusted to the target reader


The translator should know the characteristics of the target reader
in order to create a document which fulfills its purpose.

If the translator does not know your reader – he/she should not
translate.
Not knowing the target reader is dangerous and may lead to
crucial safety risks.




  12
INTRODUCTION – cont.


Safety risks to who?
Examples:
• The volunteer
• The volunteer's partner
• The volunteer pregnant partner
• The unborn child
• Family members (including children & elderly)
• Family friends
• Neighbors / The community
• The society / the study
• The environment
      ANYONE ENGAGED OR INVOLVED IN THE STUDY
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 PART 1:
 Poor Translation of Clinical Trial Documents -
 Safety Risks to the Volunteer

1. Hazards in medication therapy
   (both when self administered or given by others) –
   Increase occurrence or severity of AEs

Examples: poor translation of:
            - Prescription and administration of the trial medication:
                            name, dosage, route of administration
- Signs and symptoms to be looked for
            - failure of the clinical trial team to elicit participant's symptoms
             - Steps the volunteer or family may take to
                                       prevent or minimize AEs
            - Explanation of how and by whom the AE will be
                                       treated, and to what medical
                                       and chronological extent
            - Explanation of how the study drug affects the
                                      standard treatment the patient
                                      is receiving

  14
       PART 1: Safety Risks to the Volunteer – cont.




    The participant's limited ability to understand documents at a level that
      permits effective interaction with the clinical trial team leads to
         • failure of the participant to act as instructed
         • disparities in prescription and administration of the study
           preparation
         • reduced likelihood for appropriate follow-up and treatment of the
           underlying conditions and/or of side effects of the trial

It is CRUCIAL for these explanations to be translated clear and accurately in
     a language understandable by the staff, patient and family




        15
        PART 1: Safety Risks to the Volunteer – cont.

       2. Risks due to cultural differences, not properly adjusted by the
          translation
Examples:
   English text invites people to a clinic examination. In some countries this
    should be modifies to house calls (in order to cover a family disease).
   Food / beverages prohibited in certain religious (alcohol).
   Is “room temperature” the same in Israel and Norway?
   Questionnaires – risk of scoring differently than others around the globe
         Verbal memories – recalling lists of words
         BUT – words like “mink” and “lawn” are not usable in Israel, “cottage”
                means cheese, China” means only a country

        Letter fluency - naming as many items as possible that begin with that
                        letter




         16
         PART 2:
         Poor Translation of Clinical Trial Documents -
         Safety Risks to others

Examples:
The participant's partner: misunderstanding regarding diet, sex relations
   (contraception - when, for how long, which?), behaviour, daily activity, mood
Participant's pregnant partner: unclarity regarding hazards to pregnancy / fetus
Unborn child of a participant / participant's partner: genetic hazards to future
   generations
Family members and friends: errors in translation of storage and precautions required
Community: errors in precautions – infections, contaminations.
Society / Study: errors in reporting safety data to be analyzed for registration,
   development of drug resistance
Environment: errors in instruction of disposal of radioactive ingredients, TB live
   vaccines




           17
  PART 3:
  Common problems of poor translation


1. Lack of professional medical background

1a. Medical vocabulary – using the right term:

Example - anatomy:
• Both breasts (pupils) are equal and reactive to light and
   accommodation.

Example: pathology:
• Occasional, constant infrequent headaches
   (Occasionally, infrequent persistent headaches)




    18
         PART 3: Common problems – cont.


        More Examples:



•   She had no shaking chills, but her husband states she was very hot in bed
    last night.
    (She had no shaking chills but her husband states that she had high
    temperature / fever in bed last night).
•   When she fainted, her eyes rolled around the room.
    (When she fainted she rolled her eyes around the room).
•   Discharge status: Alive, but without my permission
    (Discharge status: Alive. Discharged without my permission).




          19
   PART 3: Common problems – cont.




1b. Jargon – new areas ahead of language
Language in science is dominated by 2 contradictory trends:
                 Greater international unification - globalization of
                    scientific English
                 Growth of field-specific jargon - new terms to express
                    new knowledge

“Jargon” allow specialists to communicate precisely with one another.

Removing jargon or substituting it with another phrase can affect
  interpretation.

Cat scan – is it “searching for kitty?




     20
      PART 3: Common problems – cont.




Problem – same words used in different jargons mean different things

(What is Plasma? Is it in the cell? Is in the blood? Is it a sterilization device
  or a part of your TV screen?

THE DECISION IS DEPENDANT ON KNOWING THE TARGET READER!




       21
     PART 3: Common problems – cont.




Slang – a popular jargon
• Doc
• Over the counter
• Gay participants – are they merry?!
•    The pelvic exam will be done later on the floor
      (The pelvic examination will be done later, in the ER department
      (which is always on the ground floor and often called “the floor”).

•     Dr. Smith felt we should sit on her abdomen
      (Dr. Smith felt we should discuss her abdomen
      (‫.)ד"ר סמית חשב שצריך לשבת על הבטן שלה‬

•     Outpatient - A patient who has fainted?




       22
    PART 3: Common problems – cont.




1c. Acronyms and abbreviations
FDA, ICH, IEC, IRB, WHO, EMEA, PI, MedDRA, CRF, AE/SAE…

Professional background enables choosing the right full term for
   the reader:
Example:
FDA: Food & Drug Administration ? / Functional Data Analysis ? /
     Florida Dental Association ? / Foreign Disaster Assistance ? /
     Frequency Domain Analysis ? / Federal Disaster Area ?

And knowing when they suit the professional reader
Example:
    The SOP reg. an AE of abnormal AST (SGOT) or ALT (SGPT) levels, but
       normal AUC or AUC(0-t), requires using the ANCOVA model. BMI, BP,
       Bpm, HR, EF and ECG results will be documented in the CRF. IV PKs,
       even when NCS or WNL will be expressed in mgs per mls.


      23
    PART 3: Common problems – cont.




2. Lack of knowledge of local and international health regulations,
    clinical trials procedures, lack of commitment to GCP
    requirements
Example: Length – a profound problem!


knowledge of local and international health regulations, clinical trials procedures,
   and GCP requirements enables quality suggestions of shortening, if requested.




      24
    PART 3: Common problems – cont.


    3. Lack of linguistic skills:
Tense
The past tense prevails in biomedical reports, except for “general
truths,” which are written in the present tense.
    • The medication improves weakness.
    • The medication improved weakness.

Future tense should be used in protocols but may confuse issues about
standard practices.
    • Environmental controls will be set to maintain temperatures of 18o to
    26oC.
    • Environmental controls are set to maintain temperatures of 18o to 26oC.




     25
  PART 3: Common problems – cont.




                  Numbers
Doses, timetable of procedures, amounts of blood to be taken,
etc.:
Inaccuracy may be critical, even fatal.
Commas simplify the reading large numbers (23,450 vs. 23450)
but:
                  Many Europeans use the decimal point as a
                  comma, rather than a period (e.g. 23,450
                  means 23.450)




   26
PART 3: Common problems – cont.



Never trust the auto speller – read again!:
      • Examination of genitalia reveals that he is circus sized.
        (Examination of genitalia revealed that he is circumcised).
      • While in ER, she was examined, x-rated and sent home.
        (While in ER she was examined, X rayed and sent home)
      • The lab test indicated abnormal lover function.
        (The lab test indicated abnormal liver function).
      • The skin was moist and dry

        (The skin was mostly dry)




 27
    PART 3: Common problems – cont.




4. Lack of translation skills:
4a. Lack of outmost preciseness
•   Using the signs > / < / = / ± / ≥ / ≤ in translating inclusion /
    exclusion criteria
•   The patient has no previous history of suicides.
    (The patient has no previous history of suicide attempts.)
•   On the second day the knee was better and on the third day it
    disappeared.
    (On the second day the knee was better and on the third the pain
    / swelling disappeared.)




      28
   PART 3: Common problems – cont.




4b. Lack of computer skills

Use of different programs, (online and hard copy)
   dictionaries, templates.

High knowledge of implementation of footers, remarks,
   comparison of documents, tabulating etc.




    29
  PART 3: Common problems – cont.




4c. Inconsistency
Typical of documents with multiple contributors
   (protocol, clinical report, ICF).
all along the document internal consistency is important
    regarding:
    •    Language - level and terms used
    •    Style
    •    verb tense

    •    Structure




    30
  PART 3: Common problems – cont.




Inconsistency – example:

The study product will be given to the subject by the investigator.
   The study doctor will administer the investigational preparation
   by injecting the experimental solution to the participant. After
   receiving the pharmaceutical experimental product, the patient
   will be requested by the physician to lie down in order to
   receive additional trial drug.

         The participant, the PI, the study drug – one term!




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PART 4:
Understand the cost of poor translation




      Physical / emotional harm

      Misconduct of the trial

      Money

      Time




32
 PART 5:
 Fundamental Skills Needed for High Quality
     Translation of Clinical Trials Documents
     – minimizing errors and safety risks
A translator who knows the target reader
with:

1. Professional medical background (vocabulary, jargon, acronyms,
   abbreviations; knowing when and how to seek dictionaries, text books,
   specialists' assistance

2. Profound updated knowledge of relevant local and
      international regulations and procedures (The ability to simplify
        the text, the knowledge to suggest solutions)

3. High linguistic skills (tense, grammar)

4. High translation skills (outmost accuracy, computer skills, consistency)



   33
     Thank you for listening!




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