Informed Consent: Evidence and Practice 4 12... · 2018. 4. 18. · Flyer. Opportunities for Respect and Promoting Equitable Selection. Options. ... (2015) Participants' understanding

Informed Consent: Evidence and Practice

Holly Taylor, PhD, MPHJohns Hopkins Bloomberg School of Public Health

Johns Hopkins Berman Institute of Bioethics

Summary

• The informed consent process is only one opportunity among many to convey respect to potential research subjects.

Objectives

• Identify the moral and practical application of respect for persons

• Identify respectful approaches to recruitment• Evaluate how best to obtain informed consent

in your research

Moral and practical applications of respect for persons

Principle of Autonomy

• Conditions for Autonomy– AGENCY self rule– LIBERTY free from controlling influences

• Autonomous Action• Respect for Autonomy

Principle of Autonomy

• Autonomous Action– Intentional– With understanding– Without controlling influence

• Respect for Autonomy– Right to hold views, make choices, take actions

Researcher responsibility to guarantee ‘space‘ in which this can happen

Belmont Report

• Ethical Principles and Guidelines for the Protection of Human Subjects of Research Three Principles

• Beneficence• Respect for Persons• Justice

Source: National Commission (1978)

Respect for Persons

• Respect for Persons– Moral requirements

• Respect each individual as an autonomous agent

• Promote autonomous action– Free from influence and with understanding

• Protect those with diminished autonomy

– Practical application• Informed consent


Justice

• Justice– Moral requirement

• Equals should be treated equally

– Practical applications• Fair procedures for selection of study subjects

– Individual

– Social


Respectful approaches to recruitment

Policy Functions of Consent

• Promotion of Public Trust• Adherence to Regulatory Compliance• Promotion of Professional Integrity of

Research and Researchers

Source: Dickert et al (2017)

Policy Functions of Consent

• Promotion of Public Trust• Adherence to Regulatory Compliance• Promotion of Professional Integrity of

Research and Researchers


Extend to Recruitment

Policy Functions of Recruitment

• Promotion of Public Trust– Social value of process– Assuring public that individuals involved in

decisions to enroll

• Promotion of Professional Integrity of Research and Researchers– Demonstrates and promotes respect for

participantsSource: Dickert et al (2017)

Policy Functions of Recruitment

• Promotion of Professional Integrity of Research and Researchers– Investigators (Institutions) impose risk and

burdens on subject – Obligation to recruit correctly and when

appropriate– Demonstrates and promotes respect for

participants


Consent Process Enrollment

First Study Visit

Last Study Visit

Share Study Results

KEY INTERACTIONS

OTHER INTERACTIONS

IncidentalFindings

ResearchResults

New StudyInformation

Time

METHODS OF RECRUITMENT

Patients

Mail on Behalf ofProvider

MyChart

AdvocacyOrgan.

MyChartProviderInteraction

General Public

Mass Media

SocialMedia

ClinicFlyer

Opportunities for Respect and Promoting Equitable Selection

Options

How best to obtain informed consent

Basics Elements of Consent

• Threshold– Competence– Voluntariness

• Informational– Disclosure– Understanding

• Consent– Decision– Authorization

Source: Beauchamp & Childress (2012)

Basics Elements of Consent

• Threshold– Competence– Voluntariness

• Informational– Disclosure– Understanding

• Consent– Decision– Authorization

Source: Beauchamp & Childress (2012)

Disclosure

• Description of Study– Purpose– Procedures– What is Experimental

• Foreseeable Risks• Benefits

• Confidentiality protections

• Alternatives• Voluntariness• Compensation for Injury• Contact information

Source: 45 CFR § 46.116

Disclosure

• As required by Common Rule 2.0– Future Use:

• Identifiers might be removed from bio-specimens and used for future research or transferred to another investigator for future use without additional consent

OR• Bio-specimens will not be used in future

Source: 45 CFR § 46.116

Understanding

• Assessment of Understanding– Individual obtaining consent has an obligation to

find out whether the subject understands enough for consent to be meaningful.

Do you have any questions?


NO.


May not have understood enough to have any.

Does not provide you with any confidence about their knowledge

Challenges

1. Many subjects do not understand key information about the studies in which they enroll

2. Consent forms are long and complex3. Interventions developed to improve the

informed consent process have had mixed results

Source: Tam et al (2015); Flory and Emanuel (2004); Nishimura et al (2013)

Challenges

4. Intervention studies to date have been conducted in simulated settings, and

5. No reliable/valid tool exists to assess subject understanding

Source: Flory and Emanuel (2004); Nishimura et al (2013)

Specific Aims

• Develop study materials for a future, large, multi site, randomized trial comparing standard to enhanced informed consent procedures in ongoing clinical research studies, and

• Determine the feasibility of conducting such a future trial by conducting a pilot trial of simple consent interventions and data collection materials and procedures in studies at the Johns Hopkins Medical Institutions.

Funded by the National Institutes of Allergy and Infectious Diseases R21AI074005

Proposed Interventions

• Consent Form– Style– Format

• Consent Process• Directed Feedback

Revised Consent Form Intervention• Time intensive• Non-reproduce-able• Reluctance to revise forms

among those conducting multi-site NIH or Pharma trials

• Develop fact sheet to supplement consent process

– Collaborate with study team

Fact Sheets

• Median length of parent study consent forms was 8.8 pages (range 6-15)

• Fact sheets were 1-2 pages and had median of 12 bullets

• Compared to parent study consent forms, fact sheets were, on average, 1.4 grades lower (8.3 v. 6.7) as measured by Fleisch-Kincaid readability scores

Directed Feedback

• Understanding is improved when patients or subjects must verbalize information, and

• Understanding is improved by administering quizzes and correcting inaccurate responses

VOICE

Source: Kass et al (2014)

Consent Assessment• Assessment of Understanding

– Six tools in the literature• 3 developed for specific disease/condition population

– Borrowed most from: • Deaconess Informed Consent Comprehension Test (DICCT) • Brief Informed Consent Evaluation Protocol (BICEP)

– Consent Understanding Evaluation (CUE)• 50 open and closed-ended questions. • Most items are generic to research

– Few specific to the study under consideration– Reflect items highlighted in summary

• Others measure attitudes, opinions & demographics

Source: DCCT Group (1989); Sugarman et al (2005)

StandardForm

Stage 1:Standard

Stage 2:Intervention 1

CUE CUE

VOICE

REALMREALM

VerbalizationFeedback

LiteracyAssessment

UnderstandingAssessment

DigitallyRecorded

Stage 3:Interventions 1 & 2

StandardForm

CUE

REALM

Fact Sheet

StandardForm

Fact Sheet

Findings

• Collaborated with 11 parent studies; 3 did not meet minimum enrollment criteria

• 145 subjects enrolled, 1 asked data to be removed


“…patients receiving both bulleted fact sheets and a Q&A session had higher understanding compared to standard consent.”

Findings

Findings

• Sample Demographics (n=145)– 67% Female– 51.5 Average age– 54% White/42% Black– 55% Not employed– 76% REALM: High School – 53% Previous enrollment in research– 50% Good health status


Findings• Without controlling for other variables, being

in Arm 3 scored 6 percentage points higher on open-ended CUE score compared to being in Arm 1, and 3 percentage points higher when compared to being in Arm 2 (p = .25).– Predictors of better score on open ended:

White/Employed/ Higher Income/Better REALM score


Findings

• Regression analysis of open-ended CUE scores predicted a 7.6 percentage point increase in score for Arm 3 compared to Arm 1 (p=.02) and a 1.6 percentage point increase compared to Arm 2 (.81).– Income also predicted higher scores (p=.05)


Findings

• Regression analysis of overall CUE scores found no statistically significant differences but trends favored:– Higher REALM score– Past research experience– Having health insurance


• Specific Aims– Create two prototype, simple, “user-friendly”

informed consent strategies designed to present key study information to potential participants:

(a) a fact sheet and (b) an interview-style video;

Current Trial

Funded by the Greenwall Foundation

Key Study Information

Common Rule to go into effect July 18, 2018

Source: 45 CFR § 46.116

• Specific Aims– Compare each of these two consent interventions

to standard (control), using a randomized design, in the context of five, ongoing, real clinical studies to determine any differences achieved in participant understanding, participant satisfaction, rates of enrollment, and length of time to administer;

Current Trial

StandardForm

CUE CUE

Signature

UnderstandingAssessmentCUE

Fact Sheet VideoStandardForm

StandardForm

Signature Signature

randomization

• Randomized Controlled Trial of an Internet Smoking Cessation Program Plus Online Social Network for HIV + Smokers

• Enhancing Medication-based Analgesia in Humans • Nano-Spectrometer Biomarker Discovery and Confirmation

Study • Clinical Trial of Air Cleaners to Improve Indoor Air Quality and

COPD Health • A Randomized Controlled Trial for Prevention of Venous

Thromboembolism following Radical Prostatectomy

Collaborating Studies

• We have approval to piggy-back on five studies

• As of Friday we have enrolled 110 of 300 subjects

Progress to Date

VOICE


Summary

• The informed consent process is only one opportunity among many to convey respect to potential research subjects.

References• National Commission, Belmont Report (1978) Available at

https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html

• Dickert NW, Eyal N, Goldkind SF, Grady C, Joffe S, Lo B, Miller FG, Pentz RD, Silbergleit R, Weinfurt KP, Wendler D, Kim SYH. (2017) Reframing Consent for Clinical Research: A Function-Based Approach Am J Bioeth 17(12):3-11.

• Beauchamp TL, Childress J. (2012). Principles of Biomedical Ethics, 7th

edition (Oxford University Press: New York).• Tam NT, Huy NT, Thoa le TB, Long NP, Trang NT, Hirayama K, Karbwang J.

(2015) Participants' understanding of informed consent in clinical trials over three decades: systematic review and meta-analysis. Bull World Health Organ 93(3):186-98H.

References• Flory J, Emanuel E. (2004). Interventions to improve research participants'

understanding in informed consent for research: a systematic review. JAMA. 292(13):1593-601.

• Nishimura A, Carey J, Erwin PJ, et al. (2013). Improving understanding in the research informed consent process: a systematic review of 54 interventions tested in randomized control trials. BMC Med Ethics 14: 28.

• Kass N, Taylor HA, Ali J, Hallez K. A Pilot Study of Simple Interventions to Improve Informed Consent in Clinical Research: Feasibility, Approach, and Results Clinical Trials 2015; (12)1: 54-66

• The DCCT Research Group. (1989) Implementation of a multicomponent process to obtain informed consent in the Diabetes Control and Complications Trial Control Clin Trials 10(1):83-96.

• Sugarman J, Lavori PW, Boeger M, et al. (2005) Evaluating the quality of informed consent. Clin Trials 2: 34–41.

Documents

Informed Consent: Evidence and Practice 4 12... · 2018. 4. 18. · Flyer. Opportunities for Respect and Promoting Equitable Selection. Options. ... (2015) Participants' understanding