D_Amendment Attachments 18.pdf

CTN Investigator Toolbox Website Study Termination: Final Study Report Preparation

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Final Study Report Preparation

Introduction and Purpose

Lead investigators will submit a final study report to NIDA CCTN within four months of database lock.

In general, the Final Study Report should include sufficient detail to allow an understanding of the study, but will focus on the data collected in the study, utilizing the planned analysis described in the protocol and Statistical Analysis plan to address the primary outcome analyses.

While the data tables may generate additional length, it is expected that the text portion of the Final Study Report will be approximately 20 pages. The following sections should be included.

1. Descriptive Information

CTN number and CTN title of the protocol. Version number and date of the last protocol

The name, node, and mailing address of the lead investigator and each co-investigator

The specific community treatment programs or sites where the study was performed

Dates for enrollment of the first participant and final evaluations of the last participant

Date of the Final Study Report, along with signature

Brief executive summary of the goals and results presented

2. Rationale and Aims of the Study (short description from the protocol)

3. Clinical Trial Design (short description from the protocol)

4. Statistical Analysis

Primary analysis only, per the original protocol and a statement of the conclusions drawn from this analysis.

Primary outcome analyses may include sensitivity of the primary outcome to missing data and investigation of site effects and interactions, consistent with the primary analysis approach defined in the protocol and/or statistical analysis plan.

Primary analysis by sex/gender and race/ethnicity per NIH Policies.

Results from any interim analysis, and any modifications made.

At the request of NIDA CCTN staff, additional analyses beyond the scope of this guidance can be added to the Final Study Report (either in the original report or as an addendum) if the analyses are critical to the understanding of the primary outcome results.

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5. Summary of Results (brief summary, include complete tables in an appendix) (may use DSMB formats and table shells)

Number of participants with a breakdown of the baseline demographic (age, race, gender, ethnicity) and clinical characteristics of each group assignment

If applicable, early termination discussion including reasons for early termination and numbers of participants

Number of participants excluded, and the reasons for exclusion

Treatment exposure and compliance

Changes in the conduct of the study, if any

Protocol violations or waivers

Problems encountered during the trial

Brief discussion on the implications of the findings (for scientific and clinical community and for future implementation).

6. Safety Monitoring (may use DSMB formats and table shells)

Summary of Data Safety Monitoring Plan (include complete DSMP as appendix)

Overall adverse events and adverse reaction data

Summary of all adverse events

Narrative for each Serious Adverse Event

Key DSMB decisions (if any)

7. Plans for archiving and storing the study records and data.

8. Authorship

The authors of the Final Study Report should sign and date the report and include in the report a brief statement describing their contributions to the report. Authors of the report should be aware that CCTN views these signatures as an affirmation that all statements are accurate and are complete representations of study activities and results and are fully supported by the data.

9. References:

Appendices:

1) Tables related to analyses listed above

2) Final protocol (including Data and Safety Monitoring Plan) and summary of protocol amendments since the start of the study

3) Statistical Analysis Plan

4) Final sample consent form

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If there are ancillary studies, then the LI must prepare a separate final study report for that ancillary study.

Any addition, deletion, or correction to the Final Study Report should be in the form of an amendment by the authors. The amendment should identify each part of the Final Study Report that is being added, deleted, or corrected and the reason(s) for the addition, deletion, or correction, and should be signed and dated by the authors.

The CTN DSMB will review the final study report and provide recommendations regarding appropriateness of study conclusions.

Adapted from:

Altman, Douglas G. et al. 2001. “The revised CONSORT statement for reporting randomized trials: Explanation and elaboration” Annals of Internal Medicine 134(8): 663- 694.

http://www.fda.gov/cvm/guidance/cigfinal.pdf

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, “Structure and Content of Clinical Study Reports” Step 4, 30 November 1995. Published in the Federal Register on July 17, 1996 (61 FR 37320).

Spilker, Bert. 1991. Guide to Clinical Trials. New York: Raven Press.

References:

Altman et al., 2001, page 665: Table 2: Checklist of items to include when reporting a randomized trial.

International Conference on Harmonization. 1996. “Guidance for Industry E6: Good Clinical Practice Consolidated Guidance.” (Federal Register Vol. 62, No. 90, May 9, 1997, pp.

25691-25709).

Krzyzanowska MK, Pintilie M, Tannock IF. 2003. “Factors associated with failure to publish large randomized trials presented at an oncology meeting” JAMA: Journal of the American Medical Association 290 (4): 495-501 July 23, 2003.

Misakian AL, Bero LA. 1998. “Publication bias and research on passive smoking - Comparison of published and unpublished studies” JAMA: Journal of the American Medical Association 280 (3): 250-253 July 15, 1998.

Moher, David et al; The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials; Lancet, Volume 357, Issue 9263, 14 April 2001, Pages 1191-1194 http://www.fda.gov/cvm/guidance/cigfinal.pdf

Data Management and Sharing (DMS) Plan Template, v1.0 June 13, 2023

This DMS Plan template uses the NIH Standard Template with modifications to 1) describe the sharing of data obtained from studies conducted with the National Drug Abuse Treatment (NDAT) Clinical Trials Network (CTN) and 2) posting of data to the NIDA Data Share website.

Note that a study’s DMS Plan may require review and possible revisions after data collection is completed and prior to manuscript preparation.

How to Use this Template

• If a particular section is not applicable to your study, please retain the section and indicate that it is not applicable by writing “N/A” under the section heading.

• This template contains two types of text: instruction/explanatory text and example text.

o Instruction/explanatory text is indicated by italics and should be deleted prior to finalizing the DMS Plan. This text provides information on the content that should be included. Instructional text should be deleted prior to finalizing the DMS Plan.

o Example text (indicated in “quotations” in regular font) is included to further aid in writing and should be modified as needed, or it may be deleted if it is not relevant. Within example text, a need for insertion of specific information is notated by <angle brackets>.

• Additional guidance text from the NIH Standard Template appears at the top of the next page (the first page of the template).

Additional Resources:

NOT-OD-21-013: Final NIH Policy for Data Management and Sharing NOT-OD-22-214: Supplemental Information to the NIH Policy for Data Management and Sharing: Responsible Management and Sharing of American Indian/Alaska Native Participant Data Writing a Data Management & Sharing Plan | Data Sharing (nih.gov) https://grants.nih.gov/sites/default/files/DMS-Plan-blank-format-page.docx https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-013.html https://grants.nih.gov/grants/guide/notice-files/NOT-OD-22-214.html https://grants.nih.gov/grants/guide/notice-files/NOT-OD-22-214.html https://grants.nih.gov/grants/guide/notice-files/NOT-OD-22-214.html https://sharing.nih.gov/data-management-and-sharing-policy/planning-and-budgeting-for-data-management-and-sharing/writing-a-data-management-and-sharing-plan

OMB No. 0925-0001 and 0925-0002 (Rev. 07/2022 Approved Through TBD)

V1.0 6.22.2023

DATA MANAGEMENT AND SHARING PLAN

If any of the proposed research in the application involves the generation of scientific data, this application is subject to the NIH Policy for Data Management and Sharing and requires submission of a Data Management and Sharing Plan. If the proposed research in the application will generate large-scale genomic data, the Genomic Data Sharing Policy also applies and should be addressed in this Plan. Refer to the detailed instructions in the application guide for developing this plan as well as to additional guidance on sharing.nih.gov. The Plan is recommended not to exceed two pages.

Text in italics should be deleted. There is no “form page” for the Data Management and Sharing Plan. The DMS Plan may be provided in the format shown below.

Public reporting burden for this collection of information is estimated to average 2 hours per response, including the time for reviewing instructions, searching existing data sources, gathering, and maintaining the data needed, and completing and reviewing the collection of information. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to: NIH, Project Clearance Branch, 6705 Rockledge Drive, MSC 7974, Bethesda, MD 20892-7974, ATTN: PRA (0925-0001 and 0925-0002). Do not return the completed form to this address.

Element 1: Data Type

A. Types and amount of scientific data expected to be generated in the project:

Summarize the types and estimated amount of scientific data expected to be generated in the project.

This section should describe the target sample size, the level at which data collection will occur (e.g., individual, site, aggregate), and the type of data (e.g. demographic, clinical, genetic, imaging, survey, interview, laboratory, etc.).

“CTN-<XXXX> will enroll approximately <X> consenting participants. Scientific data generated from this study will include <individual>-level <demographic, clinical, laboratory, survey, qualitative, interview, medical record> data.”

B. Scientific data that will be preserved and shared, and the rationale for doing so:

Describe which scientific data from the project will be preserved and shared and provide the rationale for this decision. Note that investigators will be responsible for obtaining the necessary permissions for sharing data derived from electronic medical records (e.g., appropriate Data Use Agreements). For specific considerations regarding best practices for the management and sharing of AI/AN participant data, see NOT-OD-22-214: Supplemental Information to the NIH Policy for Data Management and Sharing: Responsible Management and Sharing of American Indian/Alaska Native Participant Data.

“De-identified <demographic, clinical, laboratory, survey, qualitative> data collected from case report forms (CRFs) will be preserved and shared.

The following data will be preserved but not shared as they may contain a large volume of personally identifiable information (PII) <data derived from qualitative interviews, genetic sampling, participant locator and other administrative forms, such as supply/medication inventory forms. Likewise, data from all free-text and/or comments fields will not be shared due to the nature of the data and risk of exposing

PII.>”

C. Metadata, other relevant data, and associated documentation:

Briefly list the metadata, other relevant data, and any associated documentation (e.g., study protocols and data collection instruments) that will be made accessible to facilitate interpretation of the scientific data.

“The following materials will be posted for CTN-<XXXX>, with the file format noted in parentheses:

• De-identified trial datasets (SAS, ASCII)

• Annotated CRFs (PDF) will provide the question number, question text, variable name, response options and value labels, and standard codes for missing values—including codes for non-applicable, “don’t know,” and refusal.

• Data dictionary (Excel), which contains the variable-level metadata including variable names, variable labels, value labels, and standard codes for missing values—including codes for non-applicable, “don’t know,” and refusal https://sharing.nih.gov/

• Final version of the study protocol (PDF) <The Investigators can provide an abbreviated protocol for sharing purposes, attached with the final study report>

• CRF Level Data De-Identification Notes and Database Descriptions (PDF)

• Reference to study primary manuscript and ClinicalTrials.gov link”

Element 2: Related Tools, Software and/or Code:

State whether specialized tools, software, and/or code are needed to access or manipulate shared scientific data, and if so, provide the name(s) of the needed tool(s) and software and specify how they can be accessed.

“Scientific data will be processed and analyzed with SAS and shared in SAS and ASCII formats.”

Element 3: Standards:

State what common data standards will be applied to the scientific data and associated metadata to enable interoperability of datasets and resources, and provide the name(s) of the data standards that will be applied and describe how these data standards will be applied to the scientific data generated by the research proposed in this project. If applicable, indicate that no consensus standards exist.

For studies using PhenX Tier 1 assessments, see example text below (modify as needed):

“This study will use assessments from the Substance Abuse and Addiction Collection of the PhenX Toolkit (consensus measures for Phenotypes and eXposures), including <measures for demographics (age, ethnicity, gender, race, educational attainment, employment status, marital status), Body Mass Index (BMI), quality of life, and HIV risk and status; substance use measures include age of onset, past 30-day quantity and frequency, lifetime use for alcohol, tobacco and other substances.>”

Element 4: Data Preservation, Access, and Associated Timelines A. Repository where scientific data and metadata will be archived:

Provide the name of the repository(ies) where scientific data and metadata arising from the project will be archived; see Selecting a Data Repository). HEAL investigators must ensure that a HEAL-approved repository is selected.

Templated text below assumes use of the NIDA Data Share website (which is a HEAL-approved repository for HEAL-funded studies).

“NIDA Data Share:

The trial data sets available on the NIDA Data Share website are derived from the complete trial database. Analysis data sets such as those utilized to develop publications are not included on this website.”

B. How scientific data will be findable and identifiable:

Describe how the scientific data will be findable and identifiable, i.e., via a persistent unique identifier or other standard indexing tools.

“Data will be findable for the research community through the NIDA Data Share collection <X> months after the study is complete. A study will be identifiable via its CTN Protocol Number (CTN-<XXXX>) that was assigned when the protocol concept application was approved by the NIDA Center for Clinical Trials Network. Each participant is assigned a persistent unique identifier that differs from the ID assigned to them during the study. The crosswalk between the unique identifier and the study ID is maintained by an external contractor to protect participant confidentiality.”

https://sharing.nih.gov/data-management-and-sharing-policy/sharing-scientific-data/selecting-a-data-repository

C. When and how long the scientific data will be made available:

Describe when the scientific data will be made available to other users (i.e., no later than time of an associated publication or end of the performance period, whichever comes first) and for how long data will be available.

“Datasets for CTN-<XXXX> will be available when either (1) the primary outcome paper has been accepted for publication, (2) the data has been locked for more than 18 months, or (3) the grant concludes; whichever comes first. The datasets will remain accessible via NIDA Data Share contingent on NIDA’s continued support of the archive. To date, NIDA Data Share has not deleted any deposited data.”

Element 5: Access, Distribution, or Reuse Considerations A. Factors affecting subsequent access, distribution, or reuse of scientific data:

NIH expects that in drafting Plans, researchers maximize the appropriate sharing of scientific data.

Describe and justify any applicable factors or data use limitations affecting subsequent access, distribution, or reuse of scientific data related to informed consent, privacy and confidentiality protections, and any other considerations that may limit the extent of data sharing. See Frequently Asked Questions for examples of justifiable reasons for limiting sharing of data.

“All research participants will be consented for broad data sharing and no additional limitations other than the controls and privacy protections described below.”

B. Whether access to scientific data will be controlled:

State whether access to the scientific data will be controlled (i.e., made available by a data repository only after approval). Templated text below assumes use of the NIDA Data Share website. This information is expected to differ if an alternative repository is selected.

“Access to the scientific data generated from CTN-<XXXX> will be controlled via a registration agreement for data use on the NIDA Data Share Website. Users will have to register a name and valid e-mail address in order to download data and to accept their responsibility for using data in accordance with the NIDA Data Share Agreement.

Per the NIDA Data Share Agreement, the Recipient of the data agrees:

• Not to use the received data, either alone or in conjunction with any other information, in any effort whatsoever to establish identities of any of the subjects from whom the data were obtained

• To retain control over the received data, and not to transfer any portion of the received data, with or without charge, to any other entity or individual

• To notify the Recipient’s Institutional Review Board (IRB) operating under an Assurance approved by the Office of Human Research Protections (OHRP) as required by the Recipient's affiliated university, and in accordance with Department of Health and Human Services regulations at 45 CRF Part 46 of any new research projects based on the NIDA data. This requirement is university-specific and is not necessary for data uses such as teaching resources

• To acknowledge the NIDA database and the specific trials accessed in all oral and written presentations and publications resulting from analyses of the received data. NIDA data should be cited as follows: “The information reported here results from secondary analyses of data from clinical trials conducted by the National Institute on Drug Abuse (NIDA). Specifically, data from CTN-<XXXX> were included. NIDA databases and information are available at.”

• To maintain security and privacy of the received data for as long as necessary per local and federal requirements.

• That the NIDA or its affiliates may contact you concerning publications or other issues regarding use of the data.”

https://sharing.nih.gov/faqs#/data-management-and-sharing-policy.htm https://sharing.nih.gov/faqs#/data-management-and-sharing-policy.htm

C. Protections for privacy, rights, and confidentiality of human research participants:

If generating scientific data derived from humans, describe how the privacy, rights, and confidentiality of human research participants will be protected (e.g., through de-identification, Certificates of Confidentiality, and other protective measures).

“Privacy and confidentiality protections consistent with applicable federal, Tribal, state, and local laws, regulations, and policies will be followed. CTN-<XXXX> has a Certificate of Confidentiality that further protects the privacy of human research participants. Prior to sharing, data will be de-identified by programmatically removing or modifying all 18 HIPAA identifiers, as well as transforming all patient IDs to factless key values bearing no relationship to the collected study data. The full scope of de-identification processes will be outlined in the Data De-Identification Notes document for this study.”

Element 6: Oversight of Data Management and Sharing:

Describe how compliance with this Plan will be monitored and managed, frequency of oversight, and by whom at your institution (e.g., titles, roles).

“The project’s Lead Investigator is responsible for monitoring and complying with this Data Management and Sharing Plan. The plan will be implemented and managed by professional staff working under the direction of the PI.

NIDA’s external contractors will manage and monitor the transfer, de-identification, and posting of CTN data to the NIDA Data Share Website.”