The clinical trial readiness checklist is a tool which can help new and experienced researchers prepare for upcoming clinical studies. It is designed to be a quick reference to ensure that you have the basic requirements for conducting clinical studies, however does not replace the sponsor protocol requirements, Health Canada/FDA regulations or Research Ethics Board considerations. HOW IT WORKS: REQUIRED: The items listed under the REQUIRED category are the basic items needed for the conduct of any clinical study. Sites should ensure that they have required staff, space and equipment, training and resources to successfully conduct the study. RECOMMENDED/OPTIONAL: The items listed under the RECOMMENDED/OPTIONAL category are protocol and site specific. Not all items will be necessary for you to conduct a clinical study, so simply check off the ones that you have and make a note to speak to the sponsor about additional items required for the protocol. PROCESS OVERVIEW: This section provides a glimpse into the documents, activities and considerations required in the process of conducting a clinical study. FUTURE WORK: This toolkit should be reviewed and updated annually, or at least, as guidance documents, federal regulations and ethical considerations are updated. This is meant to be a dynamic document which can be tailored for different clinical trials related to different therapeutic areas. the needs of disease-specific clinical study requirements. It will be updated as required. Page 1
Staffing Resources Required Principal Investigator, MD (Medical Degree is protocol dependent) Optimal to have experience in clinical trials, as s/he ultimately must take personal responsibility for all aspects of study and the delegation of tasks. Optimal to be on-site whenever study subjects are being assessed. Study Coordinator This is usually a clinically trained individual with specific training in the conduct of clinical trials. It is most often a nurse. This person is often involved in all aspects of the study including ethics submission, all prestudy set up (lab draws, ECG, pharmacy, etc.) as well as actual study related activities which may include blood draw, ECGs and some of the rating scales (including cognitive testing), therefore experience is required. An understanding and appreciation of the unique challenges in dealing with HD is important. Recommended/Optional Co-Investigator or Back up Investigator This individual must understand the protocol, and should be available to fill in for the PI when s/he is away on leave, vacation or becomes ill and cannot continue the PI role. Research Manager This applies to sites that are likely to have many active studies. This individual will provide project management and oversee the conduct of the research program. Experience in clinical trial design and conduct are an asset. Manager will oversee start-up of projects, negotiation of contracts, ethics committee submissions, protocol compliance, interaction with the monitor, and other activities throughout the course of the study and closeout. Independent Rater Some studies require an independent rater blinded for study procedures. This person can be a physician, however this varies according with the protocol and what is being rated. Research Assistants/Associate Research assistants/associates assist with the setup of a research visits, may help with lab samples with spinning blood and shipping to labs, as well as data entry. Research assistants/associates may be trained in post-graduate specialized programs focusing on clinical trials but are usually not nurses or other allied health professionals. Phlebotomist /ECG Technician Ability to draw, prepare and ship blood and other biological specimen samples the needs of disease-specific clinical study requirements. It will be updated as required. Page 2
Space and Equipment Required Physical facility to conduct studies including sufficient space to assess patients, as per protocol Room for coordinator/monitor to work Secure controlled area with limited access and locked for investigational new drug (IND) or investigational product (IP), with appropriate air temperature and humidity conditions that require daily monitoring and documentation. Internet access with appropriate security measures. Ability to provide access to EMR or clinical records for visits and sponsor monitors Ability to store study related material for the required 25-year period (either on site or via third party) The equipment needed is protocol specific and may be on-site or within close proximity Freezer (-20 C) Freezer (-70 C) Fridge (2-8 C) Centrifuge Annual calibration of specific equipment ECG Ultrasound or MRI X-ray if required Internet (wireless) access IVRS experience EDC experience Experience with electronic patient diaries the needs of disease-specific clinical study requirements. It will be updated as required. Page 3
Training Required Good Clinical Practice (GCP) Recommended IATA Certification Provides certification and ability to ship dangerous goods with courier company access to site. Tri-Council Policy Statement (TCPS) Tutorial Standard Operating Procedures (SOPs) for the conduct of clinical trials (These could be purchased and customized, or generated by the site. They should be review and updated annually and available for monitor review). Links: GCP: Training can be provided by the sponsor at no charge. Reading material at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/ich/efficac/e6-eng.php TCPS: http://www.pre.ethics.gc.ca/eng/education/tutorial-didacticiel/ IATA: http://www.mayomedicallaboratories.com/education/online/dangerousgoods/ the needs of disease-specific clinical study requirements. It will be updated as required. Page 4
Additional Considerations Required Recommended Optional Sufficient number of patients to reasonably be able to recruit into trials Diverse patient population Participation in database studies such that you can identify candidates for clinical trial recruitment. i.e. ENROLL HD Ability to reimburse patients for travelling expenses (as per study budget) and to manage financial reporting of expenses. Database of patients and clinical characteristics. the needs of disease-specific clinical study requirements. It will be updated as required. Page 5
Expectations for the Conduct of a Clinical Trial Process Overview Before the Clinical Trial Commences: Rule #1 If it is not documented, it did not happen. Document and file everything. Site feasibility questionnaires and possible pre-selection visit Investigator Meeting attendance Preparation and submission of regulatory and ethics documents Create REGULATORY BINDER where copies or originals of all documents are collected Negotiation of Clinical Trial Agreement (CTA) and study budget Curriculum vitae and/or other relevant documents evidencing qualifications of investigator(s) and sub-investigator(s) Information given to potential study participants, ONLY UPON REB APPROVAL: Most up to date, REB Approved, Informed Consent Form (including all applicable translations) REB Approved Advertisement for subject recruitment (if applicable) Insurance statement (where required) Signed agreement between involved parties, e.g.: Investigator/institution and sponsor Investigator/institution and CRO Sponsor and CRO Investigator/institution and authority(ies) (where required) Dated, documented approval/favourable opinion of REB of the following: Protocol and any amendments CRF (if applicable) Informed consent form(s) Any other written information to be provided to the subjects Advertisement for subject recruitment (if used) Subject compensation (if any) Any other documentation given approval/favourable opinion REB committee composition and REB attestation (form or clause) in Canada Regulatory authority(ies) authorization/approval/notification of protocol (where required) Up to date version of the study Protocol. Keep all versions in regulatory binder. All staff must be trained on the protocol. Up to date version of the Investigator Brochure. Keep all versions in regulatory binder. Normal value(s)/ranges for medical/laboratory/technical procedures and/or tests included in the protocol Medical/ laboratory/technical procedures/tests (where required) Certification or Accreditation or Established quality control and/or external quality assessment or Other validation (where required) Instructions for handling of investigational product(s) and trial-related materials (if not included in IB) Decoding procedures for blinded trials All sponsor communication and reports the needs of disease-specific clinical study requirements. It will be updated as required. Page 1
During the Clinical Conduct of the Trial Management of patient selection, screening and study visit conduct. (create a participant master list, enrolment and screening list) Any revisions the following documents should be reviewed and filed in the regulatory binder: Investigator Brochure Protocol/amendment(s) and CRF Informed consent form Any other written information provided to subjects Advertisement for subject recruitment (if used) Dated, documented approval/favourable opinion of the REB of the following: Protocol amendment(s) Revision(s) of: o Informed consent form o Any other written information to be provided to the subjects o Advertisement for subject recruitment (if used) Any other documentation given approval/favourable opinion Continuing review of trial (where required) Regulatory authority(ies) authorization/approval/notification where required for: Protocol amendment(s) and other documents Updated Curriculum vitae and medical license for new investigator(s) and/or sub-investigator(s) Updates to normal value(s)/ranges for medical/laboratory/technical procedures and/or tests included in the protocol Updates of medical/ laboratory/technical procedures/tests Certification or Accreditation or Established quality control and/or external quality assessment or Other validation (where required) Documentation of investigational product(s) and trial-related materials shipment Relevant communications, including monitoring visits Letters /newsletters, Meeting notes, Notes of telephone calls Signed informed consent forms. Kept in participant binder/folder or regulatory binder Source documents. Kept in participant binder/folder. Site will develop and utilize source documents specific for each study Copies of signed, dated and completed CRFs Copies of documentation of CRF corrections Notification of originating investigator to sponsor of serious adverse events and related reports Notification by sponsor and/or investigator, where applicable, to regulatory authority(ies) and REBs of unexpected serious adverse drug reactions and of other safety information Notification by sponsor to investigators of safety information Interim or annual reports to REB authority(ies) Updated participant screening log Updated participant identification code list Updated participant enrolment log Investigational products accountability at the site Signature sheet (of all persons authorized to make entries and/or corrections on CRFs) the needs of disease-specific clinical study requirements. It will be updated as required. Page 2
Record of retained body fluids/tissue samples (if any) After Completion or Termination of the Trial Reconcile Investigational product(s) accountability at the site Documentation of Investigational product destruction Completed subject identification code list Final report by investigator to REB where required, and where applicable, to the regulatory authority(ies) Clinical study report (if applicable) Measurement of Success a. Reasonable time to start up of study including ethics approvals and contract negotiation. b. Protocol deviations should be held to a minimum. c. Few screening failures, recruited subjects meeting all inclusion/exclusion criteria. d. Reporting to Ethics Committee and sponsor within timelines identified. e. Meeting targets for recruitment. f. Quality data including data entry and source record validation. g. Excellent retention of subjects within study. h. Site protection of subject confidentiality. the needs of disease-specific clinical study requirements. It will be updated as required. Page 3