Df/Hcc Biomedical Protocol Template Log
DF/HCC BIOMEDICAL PROTOCOL TEMPLATE LOG
Date ofRevision / Section / Approx
Page / Description
8.10.2018 / 12.2 / 60 / Clarified language to be used for data and safety monitoring of CTEP protocols.
10.02.2017 / 12.2 / 60 / Replaced, “The committee is composed of clinical specialists with experience in oncology and who have no direct relationship with the study” with “The committee is composed of medical oncologists, research nurses, pharmacists and biostatisticians with direct experience in cancer clinical research.”
10.02.2017 / 12.1 / 58 / Replaced, “non CTEP protocols” with “protocols where CTRIO develops case report forms only.” This change was made throughout the section.
10.02.2017 / 7 / 39 / Added a new section 7.9.1: “In the event of an unanticipated problem or life-threatening complications treating investigators must immediately notify the Overall PI.”
10.02.2017 / 5.8 / 26 / Added, “In addition, the study team will ensure Off Treatment/Off Study information is updated in OnCore in accordance with DF/HCC policy REGIST-101.”
Removed, For Centralized Subject Registrations, the research team submits a completed Off Treatment/Off Study form to ODQ when a participant comes off study. This form can be found on the ODQ website or obtained from the ODQ registration staff.
For Decentralized Subject Registrations, the research team updates the relevant Off Treatment/Off Study information in OnCore.
10.02.2017 / 5.6 / 25 / Removed, “In the event of unusual or life-threatening complications, treating investigators must immediately notify the Overall PI, [Name] at [telephone # or pager”as this is sufficiently covered in the AE reporting section.
10.02.2017 / 4.4 / 17 / Replaced, “research nurse of data manager” with “participating site” throughout this section.
10.02.2017 / 4.3 / 17 / Replaced, “If a participant does not receive protocol therapy following registration, the participant’s registration on the study must be canceled. The Study Coordinator should be notified of cancellations as soon as possible.”
With, “If the subject does not receive protocol therapy following registration, the subject must be taken off-study in the CTMS (OnCore) with an appropriate date and reason entered.
10.02.2017 / 4.1 / 17 / Added the following to the randomization language:
Randomization can only occur during ODQ business hours (8:30am - 5pm Eastern Time, Monday through Friday excluding holidays).
10.02.2017 / 4.1 / 16 / Revised references to “protocol therapy” to read, “protocol-specific therapy or intervention.”
10.02.2017 / 3.2 / 14 / Added, “Please ensure exclusion criteria are clearly worded to describe participants who will not be eligible.”
10.02.2017 / 1.2 / 9 / Added language about primary objective.
Whenever possible, a single primary objective is preferable.
Each objective should include the specific measurement and a description of the metric that will be used. For example, “safety,” “tolerability,” and “feasibility” measures must include the specific metric that will be used to make the assessment (e.g., number of participants experiencing adverse events). “What” and “How” the outcome will be measured needs to be clearly stated.
DF/HCC recommends careful wording of objectives to facilitate ClinicalTrials.gov registration and reporting requirements. For more information, see Outcome Measures:
10.02.2017 / I / 8 / Added language for “no phase” trials without a drug or biologic. Replaced “Pilot Preliminary Study” with language explaining Early Phase I: Exploratory studies to be consistent with the phases recognized by the FDA.
10.02.2017 / Title Page / 1 / Under “Coordinating Center” replaced “multi institution” with “Multi-Center.” This change was made throughout the template.
03/22/2017 / 4 / 15 / Added randomization language.
“Remove the following paragraph if the trial is not randomized.
The eligibility checklist(s) and all pages of the consent form(s) will be faxed to the ODQ at 617-632-2295.”
“Remove the following paragraph if the trial is not randomized.
The ODQ Registrar will (a) review the eligibility checklist, (b) register the participant on the protocol, and (c) randomize the participant.”
“Remove the following paragraph if the trial is not randomized.
An email confirmation of the registration and/or randomization will be sent to the Overall PI, study coordinator(s) from the Lead Site, treating investigator and registering person immediately following the registration and/or randomization.”
09/23/2016 / Instructions / Updated the template version date: “Version Date: September 23, 2016 [ Replaces version date: January 8, 20156]”
09/23/2016 / Instructions / 2 / Replaced QACT contact information with the correct link within the DF/HCC Clinical Research Support website.
09/23/2016 / 3 / 11 / Removed the text, “and, unless otherwise specified, will be used by the DF/HCC Quality Assurance Office for Clinical Trials (QACT) in confirming eligibility.”
09/23/2016 / 5.6 / 24 / Replaced QACT contact information with the correct link within the DF/HCC Clinical Research Support website.
09/23/2016 / 12 / 56, 57 / Replaced QACT with ODQ.
01/08/2016 / Instructions / Updated the template version date: “Version Date: January 8, 2016 [ Replaces version date: July 17, 2015]”
01/08/2016 / 5.8 / 25 / Replaced, “A QACT Treatment Ended/Off Study Form will be filled out when a participant comes off study. This form can be found on the QACT website or obtained from the QACT registration staff” with “For Centralized Subject Registrations, the research team submits a completed Off Treatment/Off Study form to ODQwhen a participant comes off study. This form can be found on the ODQ website or obtained from the ODQ registration staff.
For Decentralized Subject Registrations, the research team updates the relevant Off Treatment/Off Study information in OnCore.”
01/08/2016 / 10 / 47 / Added “Note: for IND/IDE trials, follow up visits or other contact are required in order to identify SAEs during the 30 days following the end of study treatment.” to footnote c of the study calendar.
07/17/2015 / Instructions / Updated the template version date: “Version Date: July 17, 2015 [ Replaces version date: June 30, 2014]”
07/17/2015 / Instructions / Added: “All protocols submitted to the Office for Human Research Studies (OHRS) must be submitted using the most current template version. Any protocols drafted after this date must be submitted on this current template or at a minimum include all relevant changes found in “Biomedical Protocol Template Log” posted on the OHRS website. Review of your protocol may be delayed if it is not submitted on the correct DF/HCC protocol template.”
07/17/2015 / Instructions / Footer / Added a QR code in the bottom left hand footer of the protocol template instructions referencing the DF/HCC template version date. Do not remove or change this QR code. Removed “DF/HCC Biomedical Protocol Template Version 6/30/2014”
07/17/2015 / Title Page / 1 / Added: [YY-###]after DF/HCC Protocol #.
07/17/2015 / Title Page / 1 / Removed “DF/HCC Biomedical Protocol Template: June 30, 2014”. Template version date was added as a new QR code.
07/17/2015 / Summary of Changes and Title Page / i and 1 / Added a QR code in the bottom left hand footer of the protocol title page referencing the DF/HCC template version date. Do not remove or change this QR code on the Title Page.
07/17/2015 / 4.1 / 15 / Removed “and DF/PCC” from the section title. Deleted “QACT” and Replaced “with the DF/HCC Quality Assurance Office for Clinical Trials (QACT) central registration system.” With “in the Clinical Trials Management System (CTMS) OnCore.”
07/17/2015 / 4.2 / 16 / Removed “and DF/PCC” from the section title. Replaced the entire section with the following language: “DF/HCC Standard Operating Procedure for Human Subject Research Titled Subject Protocol Registration (SOP #: REGIST-101) must be followed.”
07/17/2015 / 4.4 / 16 / Added the following language as indicated in blue: “To complete the registration process, the Coordinator will follow DF/HCC Standard Operating Procedure for Human Subject Research Title Subject Protocol Registration (SOP #: REGIST-101) andregister the participant on the protocol. The coordinator will fax or email the participant study number, and if applicable the dose treatment level, to the participating site. The coordinator will also call the research nurse or data manager at the participating site and verbally confirm registration.”
07/17/2015 / 4.4 / 16 / Removed: “NOTE: Registration and randomization with the QACT can only be conducted during the business hours of 8:00 AM and 5:00 PM Eastern Standard Time Monday through Friday. Same day treatment registrations will only be accepted with prior notice and discussion with the DF/HCC Lead Institution.”
07/17/2015 / 7.9.3 / 37 / Removed references to “DF/PCC” and Changed “SAE” to “AE”
07/17/205 / 7.9.3 / 37 / Changed “24 business hours” to “1 business day” in the footnote of the table. Replaced all references to SAE with AE.
06/30/2014 / Title Page / 2 / Added “DF/HCC Biomedical Protocol Template: June 30, 2014”
06/30/2014 / Instructions / Changed the font color of instructional language from black italics to blue italics.
06/30/2014 / Header / Defined the specific protocol number information to ask for the “NCI Protocol #” and “DF/HCC Protocol #” and added “Protocol” to“Version Date” in the header.
06/30/2014 / Instructions / Changed the instructions to direct protocol format issues to the Office for Human Research Studies (OHRS) by email ().
10/7/2013 / Instructions / Added to item 9 “Contact your Disease Program Leader if questions arise in the creation of the protocol. Seek guidance from Biostatistics, Pharmacy, Nursing, etc. as appropriate. Direct protocol format issues to the Clinical Trials Education Office (CTEO) by email ().”
10/7/2013 / Summary of Changes / Replaced “shall” with “should” in the instructions.
10/7/2013 / Title Page / 2 / Added “if applicable” for Research Nurse and Data Manager.
10/7/2013 / Table of Contents / 5-6 / Updated subheadings to reflect changes within sections 5,7,8,12, and 13.
10/7/2013 / 2.3 / 10 / Added “If the specific doses and schedule of other agent(s) given as part of a standard treatment for the disease are not important in determining the objectives of the study, this should be clearly stated (e.g. CHOP as per institutional standards). However, this should only be done when the dose and schedule, including modifications, are not important in determining one or more objectives.”
10/7/2013 / 3.1.4 / 12 / Removed suggested text “Because no dosing or adverse event data are currently available on the use of [x] in participants < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.”
10/7/2013 / 3.2.9 / 15 / Added “For example, participant must be able to swallow pills.”
10/7/2013 / 4 / 15 / Paragraph 1 inserted “Dana-Farber/Partners Cancer Care” prior to “DF/HCC institution.” Within section replaced “treatment” with “therapy” or “protocol therapy.”
10/7/2013 / 5.1 / 17 / Replaced “Regimen” with “Treatment Regimen.”
10/7/2013 / 5.3 / 22 / Added “Caregiver Precautions – Describe in detail the need for caregivers to follow any specific precautions (e.g. should not be dispensed by a pregnant woman, wear gloves, use caution when cleaning up vomited matter.)”
10/7/2013 / 5.6 / 24 / Replaced subheading “Duration of Therapy” with “Criteria for Taking a Participant Off Protocol Therapy.” Added new paragraphs 3-5 “Participants will be removed from the protocol therapy when any of these criteria apply…In the event of unusual or life-threatening complications, treating investigators must immediately notify the Overall PI, [name] at [telephone #or pager].”
10/7/2013 / 5.8 / 24-25 / Replaced subheading “Criteria for Removal from Study” with “Criteria for Taking a Participant Off Study.” Updated suggested text to “Participants will be removed from study when any of the following criteria apply: lost to follow-up; withdrawal of consent for data submission; or death. The reason for taking a participant off study, and the date the participant was removed, must be documented in the case report form (CRF). A QACT Treatment/Off Study Form will be filled out when a participant comes off study. This form can be found on the QACT website or obtained from the QACT registration staff.”
10/7/2013 / 7.7-7.9, 7.14 / 36-39 / Inserted “For non-CTEP protocols only:” prior to subheading.
10/7/2013 / 7.13 / 39 / Added instruction “Include this section and text for all studies (i.e., CTEP protocols and non-CTEP protocols).”
10/7/2013 / 8.1-8.4 / 39-43 / Replaced subheadings “CTEP and/or Imaging IND Agent(s), Other Investigational Agent(s), and Commercial Agent(s)” with “IND Agent #1, IND Agent #2, Other Agent #1, and Other Agent #2.”
10/7/2013 / 11.1.3 / 51 / Added “MIBG (meta-iodbenzylguanidine)” guidelines.
10/7/2013 / 11.1.4 / 52 / Added instruction “Replace this section with other response scales when applicable.”
10/7/2013 / 12.1.2 / 56 / Added new suggested language “For non-CDUS/CMTS submissions: Investigative sites within DF/HCC or DF/PCC are responsible for submitting data and/or data forms to the QACT according to the schedule set by the QACT.” Inserted “For CDUS and CMTS submissions:” prior to existing suggested language.
10/7/2013 / 12.3 / 58 / Clarified which language to use for all multicenter trials verses CTEP multicenter trials.
10/7/2013 / 13 / 60 / Within section replaced “unevaluable” with “inevaluable.”
10/7/2013 / 13.2 / 63 / Replaced subheading “Sample Size/Accrual Rate” with “Sample Size, Accrual Rate and Study Duration.” Reworded paragraph 1 sentence 1 to “Please specify the planned sample size, justify the accrual rate (e.g., participants/year) and state the follow-up after termination of accrual if applicable.
10/7/2013 / 13.4-13.7 / 64-65 / Inserted 2 new subheadings of “Interim Monitoring Plan” and “Analysis of Primary Endpoints” between Stratification Factors and Analysis of Secondary Endpoints and renumbered the sections.
10/7/2013 / 13.6 / 65 / Reworded paragraph 1 last sentence to “If the analysis is inferential and not descriptive, the power for each endpoint to be analyzed should be discussed.” Paragraph 3 added “Instruments should be age appropriate.” Added new final paragraph “Some secondary aims are exploratory, and it may not be necessary to provide details on power and effect sizes.
10/7/2013 / 13.7.2 / 65-66 / Changed “Evaluation of Response” to “Evaluation of the Primary Efficacy Endpoint.” Reworded paragraph 1 to “Analyses should be intent-to-treat unless justification can be provided for not doing so. Specifically, all eligible participants included in the study must be assessed for response/outcome to therapy, even if there are major protocol therapy deviations.” Removed paragraph 2 “All of the participants who met the eligibility criteria…Precise definitions for categories 4-9, and sometimes category 3, will be protocol specific.” Paragraph 3 removed sentence 1 “All conclusions should be based on all eligible participants.” Reworded last sentence to “If applicable to the endpoint, the 95% confidence intervals should also beprovided.”
10/7/2013 / 14 / 65-66 / Reworded suggested text to “The results should be made public within 24 months of reaching the end of the study. The end of the study is the time point at which the last data items are to be reported, or after the outcome data are sufficiently mature for analysis, as defined in the section on Sample Size, Accrual Rate and Study Duration. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. A full report of the outcomes should be made public no later than three (3) years after the end of the study.”
10/7/2013 / Appendix BMulticenter Guidelines / 68-70 / Revised instructions to “If this is a non-CTEP multi-institution study (i.e. includes research sites external to DF/HCC or DF/PCC institutions), insert the protocol-specific DF/HCC Multi-center Data and Safety Monitoring Plan. If this is a CTEP multi-institution study, include the CTEP Multicenter Guidelines and insert the protocol-specific DF/HCC Multi-center Data and Safety Monitoring Plan.”
10/7/2013 / Appendix C Information on Possible Drug Interactions / 70-73 / Added instruction “As applicable, please include this information sheet in CTEP protocols. The information sheet should be modified to fit the protocol.”
8/14/2013 / Document / all / Reformatted to meet requirements for electronic submission to NCI. Reorganized sections from “Schema; Objectives; Background; Participant Selection; Registration Procedures; Treatment Plan; Expected Toxicities and Dosing Delays/Dose Modifications; Drug Formulation and Administration; Correlative/Special Studies; Study Calendar; Measurement of Effect; Adverse Event Reporting Requirements; Data and Safety Monitoring; Regulatory Considerations; Statistical Considerations; Publication Plan; References; and Appendices” to “Summary of Changes; Schema; Objectives; Background; Participant Selection; Registration Procedures; Treatment and/or Imaging PlaDosing Delays/Dose Modifications; Adverse Events: List and Reporting Requirements; Pharmaceutical and/or Imaging Agent Information; Biomarker, Correlative, and Special Studies; Study Calendar; Measurement of Effect; Data Reporting/Regulatory Requirements; Statistical Considerations; Publication Plan; References; Appendix A – Performance Status; Appendix B – Multicenter Guidelines; Appendix C – Information on Possible Drug Interactions; and Appendix D – Bioassay Templates.” Replacedreferences to “patients or subjects” with “participants.” Updated new section names and reference codes.
8/14/2013 / Instructions / Rewrote entire instruction section to include language and requirements for electronic submission to NCI.
8/14/2013 / Summary of Changes / i / Added new section called “Summary of Changes.”
8/14/2013 / Title Page / 1-3 / Inserted language regarding NCI investigator registration. Updated requirements for identifying the Statistician, Study Coordinator, Research Nurse and Data Manager. Inserted new language to describe IND or IDE status.
8/14/2013 / Schema / 4 / Expanded instructions to includeadvanced imaging. Removed example schematic for non-randomized trial.
8/14/2013 / Index / 5-7 / Updated headings and subheadings for consistency with new format.
8/14/2013 / 1 / 9 / Updated URL under Phase III: Comparative Study.
8/14/2013 / 1.1-1.3 / 9 / Added language and examples to facilitate ClinicalTrials.gov registration and reporting requirements.
8/14/2013 / 2 / 10 / Replaced “Study Agent(s)” with “IND Agent(s)” and “OtherAgent(s) and expanded the instructions.” Rearranged order to “Study Disease(s), IND Agent(s), Other Agent(s), Rationale, Correlative Studies Background. “
8/14/2013 / 3 / 11 / Under non-BMT section, replaced “prior to study entry” with “prior to the date of registration.” Replaced “Other non-laboratory tests” with “Diagnostic tests, such as MRIs and CTscans.” Replaced “within 30 days of study entry” with “within 30days of the date of registration.”
8/14/2013 / 3.1 / 11 / Removed introductory sentence “Participants must meet …”
8/14/2013 / 3.1.4 / 12 / Replaced “Age [x] years” with “Age 18 years.”
8/14/2013 / 3.1.4-3.1.5 / 12 / Reversed the order for Life expectancy and ECOG performance status.
8/14/2013 / 3.1.9 / 13 / Added sample language specific to men treated or enrolled on the protocol.
8/14/2013 / 3.2 / 13 / Removed introductory sentence “Participants who exhibit any …”
8/14/2013 / 3.2.5 / 14 / Expanded sample language specific to CYP450 inhibitors or inducers.
8/14/2013 / 3.2.6-3.2.9 / 14-15 / Reshuffled the order for consistency with NCI requirements.
8/14/2013 / 3.3 / 15 / Changed heading from “Inclusion of Women, Minorities and Other Underrepresented Populations” to “Inclusion of Womenand Minorities.” Added suggested text of “Both men and womenofall races and ethnic groups are eligible for this trial.” Updated instructions to reflect current NCI thinking.
8/14/2013 / 4.1 / 15 / Paragraph 2 replaced “A member of the study team will confirm eligibility criteria and the protocol-specific eligibility checklist.” With “An investigator will confirm eligibility criteria and a member of the study team will complete the QACT protocol-specific eligibility checklist.” Paragraph 3 sentence 3 replaced “protocolstatus must be changed” with “registration on the study may becanceled.” Paragraph 3 last sentence replaced “participant statuschange” to “registration cancellations.”