Informed Consent Document Editing: Best Practices

1. Informed Consent Document Editing: Best Practices Lisa Shilling-Wright, MA, CIP Team Leader, Scientific Editing

2. Presentation Topics • Why the Informed Consent Document (ICD) is edited • The process of the Scientific Editors at MD Anderson • Specifics of the Boilerplates used by the Scientific Editors

3. Health Literacy “The degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions.” US Department of Health and Human Services 2000

4. Health Literacy Statistics • 36% of adults read at or below the 7th grade reading level • 56% of adults over age 65 read at or below the 7th grade reading level • When broken down by ethnicity: 28% of Caucasian, 58% of African American, and 66% of Hispanic adults read at or below the 7th grade reading level 2003 Health Activities Literacy Survey

5. Office For Human Research Protections (OHRP) Policy The informed consent process involves three key features: (1) disclosing to potential research subjects information needed to make an informed decision; (2) facilitating the understanding of what has been disclosed; and (3) promoting the voluntary nature of the decision to participate in the research. Informed consent must be legally effective and prospectively obtained.

6. MD Anderson Policy The Institutional Review Board (IRB) of The University of Texas MD Anderson Cancer Center requires that informed consent documents (ICDs) for human subjects research are presented to the research subject at the 6th-8th grade reading level.

7. Institutional Review Boards (IRBs) • Committees of doctors, researchers, and community members • Responsible for protecting research participants (safety, ethics review) • Review new proposed research studies and revisions of ongoing studies, including the ICD

8. Scientific Editing at MD Anderson • Scientific Editing is a subset of the Office of Protocol Research (OPR) • Scientific Editors assist in the creation of ICD templates for all types of research ICDs used in the institution • Scientific Editors edit all ICDs for clinical, psychosocial, laboratory, and data review trials during initial submission and revisions

9. Scientific Editing at MD Anderson The Scientific Editors work collaboratively with the Principal Investigators (PIs), research faculty and staff, and IRBs to develop the ICD.

10. Workflow of Initial ICD Editing Process Editor makes changes and sends back to researcher with questions to answer Researcher submits ICD draft to editor for review Researcher may send it to research sponsor as well Editor receives updated draft with questions answered Researcher uses ICD in clinic to enroll participants  The IRB-approved ICD is made available to researcher IRB reviews and may make contingencies Editor finalizes draft

11. Types of Boilerplates used by the Scientific Editors • Plain Language Boilerplate • Drug Definition Database • Adverse Event Glossary • Adverse Event Database • Template Boilerplate

12. Creating the Boilerplates • New procedure/drug is included in an ICD submitted to the Scientific Editors • Scientific Editor researches the new item(s) • Scientific Editor rewrites the technical language into lay language • New description is sent back to the PI for review

13. If the PI Approves the Description • The description is reviewed at an IRB meeting • The Scientific Editor makes anyIRB-suggested changes to the description, if necessary • Description is added to the boilerplate template

14. If the PI Does Not Approve the Description • The PI revises the language • The Scientific Editor approves the revision and sends it to the IRB for review • If the Scientific Editor does not agree, it is sent to the IRB with an editor note • The IRB determines the final language to be used • The description is added to the boilerplate

15. Plain Language Boilerplate The editorial staff of OPR has developed a database of standard phrases and definitions that can be used during the creation of an original ICD. This database of terminology, or what is referred to as the Plain Language Boilerplate, includes commonly recurring medical words, phrases, and procedures, as well as procedural definitions and drug definitions. All of which are written at a 6th - 8th grade reading level.

16. Plain Language Boilerplate Examples Vital Signs: Vital signs (blood pressure, heart rate, temperature, and breathing rate) Electrocardiogram: You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart). Placebo: A placebo is a substance that looks like the study drug but has no active ingredients. Pharmacokinetic Testing: PK testing measures the amount of study drug in the body at different time points.

17. Boilerplate Consent Examples While on this study, you are at risk for side effects. These Side effects will vary from person to person. The more Commonly occurring side effects are listed in this form, as are rare but serious side effects. You should discuss these with the study doctor. You may also want to ask about uncommon side effects that have been observed in small numbers of patients but are not listed in this form. Many side effects go away shortly after treatment is stopped, but in some cases side effects may be serious, long-lasting or permanent, and may even result in hospitalization and/or death. Tell the study staff about any side effects you may have, even if you do not think they are related to the study drug.

18. Before the Edit Serum (approximately 3 tsp) for pharmacogenomics. Pharmacogenomics is the evaluation of individual genomic variations in relation to the delivery and effectiveness of drugs. Knowledge of individual genotypes and phenotypes makes it possible for physicians to customize drugs and drug delivery methods for specific subgroups.

19. After the Edit Blood (about 3 teaspoons) will be drawn for pharmacogenomic (PGx) testing. PGx testing looks at how someone's genes may influence if and how well the study drug may affect the disease.

20. Drug Definition Boilerplate The Scientific Editors have created a database of lay definitions of the mechanism of action of drugs used in the institution.

21. Drug Definition Boilerplate Before the edit: • Erlotinib is an EGFR inhibitor. The drug follows Iressa gefitinib, which was the first drug of this type. Erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase, which is highly expressed and occasionally mutated in various forms of cancer. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. For the signal to be transmitted, two members of the EGFR family need to come together to form a homodimer. These then use the molecule of ATP to autophosphorylate each other, which causes a conformational change in their intracellular structure, exposing a further binding site for binding proteins that cause a signal cascade to the nucleus. By inhibiting the ATP, autophosphorylation is not possible and the signal is stopped.

22. Drug Definition Boilerplate After the edit: • Erlotinib isdesigned to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing.

23. Adverse Event (AE) Glossary The Scientific Editors have created a glossary of over 1,750 side effects that have been translated from the technical names of the side effects to lay definitions. The glossary also includes a notation if a side effect is serious or considered non-serious.

24. AE Glossary Examples • alopecia=hair loss (partial or total) • palmar-plantar erythrodysesthesia = hand-foot syndrome (palms of hands/soles of feet with pain, swelling, and blistering) • bundle branch block = irregular heartbeat • cholecystitis = gallbladder inflammation (possible abdominal pain)

25. Adverse Event Database The Scientific Editors collaborate with researchers to edit new and revised ICDs to lower the reading level of side effect language related to study drugs. Once this language has been reviewed and approved by the IRB, it is added to the Adverse Event Database so that future investigators studying these drugs can use the same risk profiles. The database is updated regularly with new information derived from pre-clinical testing of investigational drugs, clinical trials, and post-marketing reports.

26. ICD Template Boilerplate The Scientific Editors, in collaboration with the MD Anderson legal department and IRB, have created boilerplate template language for each ICD template (Clinical, Laboratory, Psychosocial, Data Review, and Compassionate). The template boilerplate ensures that the FDA required items are included in each document at an appropriate reading level.

27. ICD Template Boilerplate Examples You will be informed of any new findings that might affect your willingness to continue taking part in the study. MD Anderson may benefit from your participation and/or what is learned in this study.

28. Benefits of the Boilerplates • Creates consistency among ICDs within the institution • Speeds creating and editing ICDs for faculty and research staff, as well as Scientific Editors • Enables the Scientific Editors to have IRB approved language available to support document changes

29. Conclusion The Boilerplate databases are an invaluable tool that fosters consistency among ICDs across the institution, while increasing the clarity of highly complex information. This facilitates the disclosure of relevant information to potential research subjects, thus allowing them to make a voluntary and informed decision about whether or not they wish to participate in the research.