Submission of an Acceptable Protocol (AP)

Once Takeda informs an investigator that their New Protocol is acceptable, the investigator must complete the Acceptable Protocol (AP) screen on the Takeda II-SR website. A completed IRS-W9 form will be required for those studies involving funding.

Funding negotiations, if required, are conducted with the External Research staff. A final negotiated budget must be reached between the External Research staff and an investigator prior to a Study Agreement being generated.

Documentation required for submission of an Acceptable Protocol to Takeda:

• Completed AP screens on Takeda website
• Final protocol
• Final Resource Request Template(s)
• Completed IRS Form W9 (if applicable)

Study Agreement

Once Takeda receives an Acceptable Protocol and all required supporting documentation, Takeda's Legal Department will prepare a draft of the Study Agreement.

The Study Agreement may be between Takeda and the investigator, or between Takeda and the institution with which the investigator is affiliated. If the Study Agreement is between Takeda and an institution, the investigator, in most instances, will be asked to agree to and sign acknowledgement of the Study Agreement as well.

In general, the Study Agreement sets forth the obligations of the Institution, Investigator and Takeda in relation to the study. The specific contents of the Study Agreement will vary depending upon the particular study; however, most Study Agreements contain language pertaining to the following topics:

• Study conduct;
• Safety requirements;
• Inventions;
• Publications and presentations;
• Confidentiality;
• Term and termination;
• Drug: amount and disbursement schedule (if applicable);
• Funding: amount and payment schedule (if applicable);
• Liability;
• Debarment;
• Patient privacy (if applicable);
• Dispute resolution; and
• Compliance with the law.

Once Takeda's Legal Department has prepared a draft of the Study Agreement, it is forwarded to the investigator and/or the investigator's institution for review. Once all parties agree on a final version of the Study Agreement, Takeda will send two (2) copies to the institution for signature. Once the institution and/or the investigator sign the Study Agreement, one fully-executed copy must be returned to Takeda.

PLEASE NOTE: All Study Agreements for II-SR projects must be fully executed within three (3) months of notification from Takeda that a NP may proceed to the Acceptable New Protocol step. If not, Takeda reserves the right to defer the study in the event this deadline is not reached.

 

Regulations

Takeda requires investigators to comply with all applicable federal/state regulations and local ordinances for clinical and/or non-clinical research. An investigator may be required (according to federal regulations) to file an Investigator IND with respect to his or her particular study.

For those studies that require IRB/IACUC approval and/or an Investigator IND, the investigator enters the date of IRB/IACUC approval and/or the date of the FDA's acknowledgement of the IND into the Takeda website.

Below please find a list of some regulations that may apply to an investigator's II-SR study:

• Title 21, Code of Federal Regulations (CFR), Part 312: Investigational New Drug Application (IND) (Subpart D: Responsibilities of Sponsors and Investigators)
• Title 21 CFR, Part 50: Protection of Human Subjects (Subpart B: Informed Consent of Human Subjects)
• Title 21 CFR, Part 54: Financial Disclosure by Clinical Investigators
• Title 21 CFR, Part 56: Institutional Review Board
• Title 45 CFR, Part 46 or 21
• International Conference on Harmonization, Harmonization Tripartite Guidelines for Good Clinical Practice (ICH) - E6 Guideline for Good Clinical Practice.
• Title 21 CFR, Part 58: Good Laboratory Practice (GLP) for Non-clinical Laboratory Studies

 

Generation of the IND:

Not all II-SR protocols require an IND. More information on filing an IND may be found at:

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/ucm071098.htm
http://www.access.gpo.gov/nara/cfr/waisidx_08/21cfr312_08.html

Additional information regarding the responsibilities of a Sponsor, an Investigator, IRB and Informed Consent requirements, and other regulatory requirements for clinical research may be found at:

http://www.access.gpo.gov/nara/cfr/waisidx_08/21cfr312_08.html
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/default.htm

PLEASE NOTE: All IRB/IACUC approvals must be received within four (4) months of notification from Takeda that a NP may precede to the Acceptable Protocol step. If not, Takeda reserves the right to defer the study in the event this deadline is not reached.

 

Clinical Registry

Certain studies are subject to the Food and Drug Administration Amendments Act of 2007 (US Public Law 110-85, HR 3580). According to the Act, certain controlled clinical trials of drugs, biologics or devices (excluding Phase I trials) must be registered by the trial's sponsor on clinicaltrials.gov and their results posted on the clinicaltrials.gov data bank (http://www.clinicaltrials.gov/). Additional details can be obtained within the Act.

To comply with federal law and ensure the ability to publish study results, investigators must register clinical trial protocol information onto the ClinicalTrials.gov website before enrolling the first patient.

Section 113 of the FDA Modernization Act of 1997 requires investigators to register protocol information related to clinical trials for serious or life-threatening diseases and conditions on the ClinicalTrials.gov website. The link below may be helpful to investigators in providing additional information on this requirement: (press the CONTROL key while clicking on the link): http://prsinfo.clinicaltrials.gov/fdama-113.html

The International Committee of Medical Journal Editors (ICMJE) issued editorials stating that the ICMJE will consider a trial for publication only if the trial has been registered before the enrollment of the first patient. To view the ICMJE editorials related to this topic, press the CONTROL key while clicking on the following link: http://prsinfo.clinicaltrials.gov/icmje.html

Investigators who are new to the ClinicalTrials.gov website must go to http://prsinfo.clinicaltrials.gov to set up an account and obtain a password prior to registering any study information.

All information registered on ClinicalTrials.gov website must be kept current at all times. Investigators are responsible for ensuring that all entries on the site are 1) updated when any changes are made to the study and 2) are reviewed at a minimum of every six (6) months. Takeda should not be listed as a Sponsor of any II-SR trial as Takeda is considered a supporter of II-SR studies. Takeda should be listed under the category of Collaborator.

 

Clinical/Drug Supplies

Investigators may request that Takeda provide drug for use in conducting an II-SR study. Once a Study Agreement has been fully executed, requests for commercial Takeda product requires a minimal lead time of five (5) business days. Takeda's ER staff will work with the investigator to supply the requested drug.

The packaging vendor includes a packing list with each shipment. The bottom half of this packing list serves as an "Acknowledgement of Receipt," which is completed and the original maintained by the investigative site. A copy must be faxed to Takeda's ER Staff at 224-554-7916 by the Investigator.

It is the responsibility of the principal investigator to maintain the clinical supplies in the appropriate conditions, track receipt, usage, and destruction and/or return. Investigators should refer to their Study Agreement for details on where to return clinical supplies.

 

Subject Safety

The Study Agreement sets forth the obligations of the Institution, Investigator and Takeda in relation to serious adverse event reporting for the study.

Whether the serious adverse event is considered a clinical or post-marketing event, Takeda requires that all information be communicated to Takeda's Pharmacovigilance Department at takedasafety@tgrd.com, Fax Number 1-224-554-1052 or Phone Number 1-866-723-9473. The investigator is also required to indicate the SAE in the monthly updates on the II-SR website.

Additional information on Reporting SAEs to the FDA may be found at: http://www.fda.gov/medwatch/REPORT/mfg.htm

 

Publications

Takeda expects investigators to publish the results of their II-SR studies in the form of abstracts and/or posters at scientific congresses or as manuscripts in peer-reviewed journals.

Each congress and journal has individual requirements (e.g., types of research papers accepted, preferred format, maximum word count, etc.). Investigators should consult the requirements that can be found under "Instructions for Authors" or "Call for Abstracts" links on the respective journal or congress website.

Investigators may contact the II-SR Call Center with any further questions at 1-877-Takeda7 extension 2 or by e-mail at iisr@tpna.com.

Many journals including JAMA, The New England Journal of Medicine, and The Lancet adhere to the International Committee of Medical Journal Editor's (ICMJE) requirements respecting manuscript format and publication ethics. Investigators should comply with the current version of The Uniform Requirements for Manuscripts Submitted to Biomedical Journals established by ICMJE as well as the other generally recognized standards concerning publication and authorship.

The ICMJE issues updates to its requirements on a regular basis. Investigators may view the current version of ICMJE requirements online at www.icmje.org.

The investigator must provide a copy of any publication to Takeda for review at least 30 days prior to submitting it for publication.