T H E I M PA C T O F L A N G U A G E + C U LT U R E - - PowerPoint PPT Presentation
T H E I M PA C T O F L A N G U A G E + C U LT U R E IMPLEMENTING MULTINATIONAL RANDOMIZED CLINICAL TRIALS MONIKA VANCE CEO | SANTIUM ISCTM AUTUMN CONFERENCE 2017 Hotel Le Meridien Etoile - Paris FRANCE September 1, 2017 ISCTM Chair:
IMPLEMENTING MULTINATIONAL RANDOMIZED CLINICAL TRIALS
ISCTM AUTUMN CONFERENCE 2017
Hotel Le Meridien Etoile - Paris FRANCE September 1, 2017 ISCTM Chair: Amir Kalali MD ECNP Chair: Eduard Vieta MD
MONIKA VANCE CEO | SANTIUM
Monika Vance | CEO | Santium
I have relevant financial relationships with the concepts described, reviewed, evaluated, or compared in this presentation. Commercial Interests & Consulting Fees – Financial compensation from Santium, with 100% ownership interest and income generated from international healthcare and pharmaceutical industries, and government agencies; providing services related to clinical outcome assessment. Speaker Honoraria – None Potential Conflict of Interest – None
The U.S. Food and Drug Administration Perspective
Growing Global Activity
U.S. + EUROPE
World’s most prolific clinical trial data collectors.
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Growth of International Clinical Trials
Based on total registered CT Investigators
U.S. Non-U.S.
Ayalew, K. (Sept. 2014). FDA Perspective on International Clinical Trials; Rate of Increase for FDA Regulated Investigators: 2000-2014 [PowerPoint Presentation]. Retrieved from www.fda.gov/downloads/drugs/newsevents/ucm441250.pdf. ClinicalTrials.gov [website] (Jan 2017). Trends, Charts and Maps [webpage]. Retrieved from www.clinicaltrials.gov/ct2/resources/trends#MapOfStudies
195 Countries 234,000 Trials
Data most impacted by language and cross-cultural challenges.
We resolve only what we learn to understand.
Sponsor + CRO Research Site Subject Rater
Trial execution Expertise & Experience Timelines Site selection methodology
Disorder
Region Outpatient vs. inpatient Study design Symptom presentation Diagnosis Titration
Drug
Efficacy Demographics Inclusion / exclusion Expectations Economic benefit Diagnostic framework & specificity Supportive environment for subjects Cultural norms Aims Expertise/Experience PI involvement Quality of ratings/scores Qualifications Clinical training & experience Managing subjects’ & caregiver expectations Attrition Attrition Budget Biases Service provider selection practices Language skill Psychopathology
Note: This diagram is an example of select elements to demonstrate level of complexity. It is not intended to represent a complete set of contributing factors affecting trial success.
Endpoint Measurement Strategy Language proficiency Trust / rapport with rater Adherence Cultural origin Etiology Mechanism of action Data entry & management practices Informed consent Informed consent Religion Cultural Communication with subjects/caregivers Data Management + Analytics Caregivers Informed consent Target accuracy
ClinROs + PROs: Subjective, culturally-biased, variable in psychometric quality; rarely adapted to converge with cultural norms.
ETIC PRIMARY OUTCOME MEASURES
Data Interpretability
Assessment, Measurement and Trial Design in Cross-Cultural Conflict
What do we understand about the disorder? What does decompensation look like at measurable critical stages?
UNDERSTANDING ETIOLOGY AND PATHOGENESIS
ICD 10/11 (51%) vs DSM (44%)*; not cross-culturally validated
VARIABLE DIAGNOSTIC CLASSIFICATION SYSTEMS
RCTs - Ideal for inquiries in somatic medicine & highly problematic in CNS:
Hypotheses based on emic clinical knowledge, inductive & abductive logic.
LIMITATIONS
*Evans, S. C., et al (2013). Psychologists’ perspectives on the diagnostic classification of mental disorders: Results from the WHO-IUPsyS Global Survey. International Journal of Psychology, 48(3), 177–193. http://doi.org/10.1080/00207594.2013.804189
Data Interpretability IMPACT OF CULTURE
Variable perceptions - pathology, cultural disorders, clinical profile, symptom severity and treatment prioritization.
EMIC CLINICAL TRAINING
UAI – Tolerance for ambiguity
UNCERTAINTY AVOIDANCE
IND – Indicator for happiness (focus
INDULGENCE - RESTRAINT
LTO – Consideration of tradition + progression + actions/challenges
LONG-TERM ORIENTATION POWER DISTANCE
INDIVIDUALISM - COLLECTIVISM
MASCULINITY - FEMININITY
PDI - Acceptance of unequal distribution of power IDV – Preference for group- based organization MAS – Success emphasis on task vs person
Geert Hofstede’s Cultural Dimensions
Hofstede, G. (1980). Culture's consequences: International differences in work-related values. Beverly Hills, CA: Sage.
Effects of Culture on Emic Societal Values + Communication + Behavior
Assessment of Society’s Persona
Communicating Potential Risks + Benefits = Understanding Cultural Differences
mentally ill)
SOCIAL CONSTRUCT
prognosis
STIGMA
exposure, inquiries about physical/ mental health, healthcare provider, spiritual healer + rituals, etc.
RELIGION
NUREMBERG CODE + DECLARATION OF HELSINKI (1964)
“In any research on human beings, each potential subject must be adequately informed of the aims, methods, anticipated benefits and potential hazards of the study and the discomfort it may entail.. He or she should be informed that he or she is at liberty to abstain from participation in the study and that he or she is free to withdraw his or her consent to participation at any time. The physician should then
Maximize Subject Recruitment Opportunities
Nijhawan, L. P., Janodia, M. D., Muddukrishna, B. S., Bhat, K. M., Bairy, K. L., Udupa, N., & Musmade, P. B. (2013). Informed consent: Issues and challenges. Journal of Advanced Pharmaceutical Technology & Research, 4(3), 134–140. http://doi.org/10.4103/2231-4040.116779
Unquestioned acceptance of ingenuous instructions from sponsor/CRO impacting psychometric integrity and quality of translation.
CLINRO + PRO TRANSLATION EXPERIENCE
availability, and relevant expertise
LOCAL “CLINICAL EXPERT” NETWORK
equivalency varies in quality (i.e. conformance + performance)
PRO Guidance + ISPOR Method – practical mechanical approach. In its
entirety, absolutely minimal method for translating PROs. Too minimalistic for ClinROs designed to measure complex constructs.
LIMITATIONS
IN EXPERTISE
“ Never trust the translation or interpretation of something without first trusting its interpreter.” Suzy Kassem
― Philosopher, Writer and Poet
ClinRO + PRO + Informed Consent Linguistic Validation PSYCHOMETRICS + TRANSLATABILITY
Linguists tasked with CD; challenges with informed consent and availability of MDs. Also use sponsor’s study sites’ resources.
ACCESS TO RATER + SUBJECT GROUPS
READING LEVEL
US Level: Gr. 6 Simple Descriptive COMPREHENSION Normal 12-yr old literate adolescent Layman terminology
CULTURAL
Communication style
(i.e. visual + somatic symptom reporting)
Expectations for change Perception of change
RX ASSUMPTIONS
Items represent equivalent construct of target disorder Items are translated with conceptual equivalency Subjects are fluent in official national language(s) Subjects are natives or accultured residents of target country
Protecting Data Integrity in Ethnically Heterogeneous Countries
Psychometric Design Basics
LINGUISTIC VALIDATION CONSIDERATIONS
READING LEVEL
Advanced Academic Technical COMPREHENSION Skilled + Technical Medical terminology
CULTURAL
Western (US-based) diagnostic + symptom profile frameworks Medical idioms & euphemisms
RX ASSUMPTIONS
Items represent equivalent construct + translated with conceptual equivalency Raters are locally trained or accultured Rater training adequately calibrates cultural differences Raters are fluently bilingual (English + Subjects’ Languages)
Protecting Data Integrity in Ethnically Heterogeneous Countries
Psychometric Design Basics
LINGUISTIC VALIDATION CONSIDERATIONS
The colloquialism + heart and soul of its people
* Erwin, S.M., Osgood, C.E. (1954). Second language learning and bilingualism. Journal of Abnormal and Social Psychology, 59, 139-146. | Lambert, W., Havelka, J., Crosby, C. (1958). Language Acquisition. Journal of Abnormal and Social Psychology, 56, 239-2
community
clinical practice treating relevant disorder(s)
BILINGUALISM* + LOCAL CLINICAL IMMERSION
and Western DSM terminology
LANGUAGE + EXPERTISE
styles of somatic and psychological symptoms + perceptions
LANGUAGE + CULTURE + SYMPTOM-REPORTING
America
CULTURE + PSYCHOPATHOLOGY
Translators + Raters Translators + Raters
TRANSLATING CULTURALLY-SENSITIVE CONTENT
LANGUAGE + CULTURE IN MULTINATIONAL CLINICAL TRIALS
UNDERSTANDING CULTURAL DIFFERENCES VALIDATE ALL TRANSLATIONS QUALIFY FLUENCY IN RATERS + TRANSLATORS DEFINITELY TRANSLATE CLINRO MEASURES Make communication with international raters and subjects crystal clear Ensure cultural sensitivities are addressed
Use the existing guidance the linguistics community uses to assess adequate fluency
Don’t leave your raters to acculture themselves to your standards; give them the tools they need to make the transition easier.
COUNTRY POWER DISTANCE INDIVIDUALISM MASCULINITY UNCERTAINTY AVOIDANCE LONG-TERM ORIENTATION Philippines 94 32 64 44 19 Mexico 81 30 69 82 China 80 20 66 40 118 India 77 48 56 40 61 France 68 71 43 86 Hong Kong 68 25 57 29 96 Poland 68 60 64 93 Turkey 66 37 45 85 Portugal 63 27 31 104 Czechia (Czech Republic) 57 58 57 74 Spain 57 51 42 86 Japan 54 46 95 92 80 Italy 50 76 70 75
49 65 63 49 USA 40 91 62 46 29 UK 35 89 66 35 25 Switzerland 34 68 70 58 Sweden 31 71 5 29 33 Denmark 18 74 16 23 Israel 13 54 47 81 Austria 11 55 79 70
0-20 21-40 41-60 61-80 81-100 101-120
Hofstede, G. (1980). Culture's consequences: International differences in work-related values. Beverly Hills, CA: Sage.
Philippines Mexico China India France Hong Kong Poland Turkey Portugal Czechia (Czech Republic) Spain Japan Italy
USA UK Switzerland Sweden Denmark Israel Austria
Filter: Power Distance
Power Distance Individualism Masculinity Uncertainty Avoidance Long-Term Orientation Implicit Global Benchmark PDI IDV MAS UAI LTO
Data Interpretability = Cultural Differences + Communication
Hofstede, G. (1980). Culture's consequences: International differences in work-related values. Beverly Hills, CA: Sage.