GCP 5. SPONSOR
(T/F) Sponsor agreements made with investigators/institutions, and or with any other parties involved in the trial must be included in the protocol.
FALSE Agreements can be defined in separate documents. 5.1.4
(T/F) There must always be on-site monitoring before, during, and after the trial.
FALSE In exceptional circumstance, central monitoring in conjunction with procedures such as investigators' training and meetings and extensive written guidance can assure appropriate trial conduct. 5.18.3
(T/F) A sponsor must provide insurance/indemnity protection to subjects and investigators even if not required by applicable regulation.
FALSE Insurance/indemnity may be provided at the sponsor's discretion, if not required by regulations. 5.8.1
(T/F) Different regulations dictate what a CRO and sponsor can do in the course of a clinical trial.
FALSE The CRO is governed by the same regulations as the sponsor once the CRO assumes trial-related duties and functions. 5.2.4
(T/F) The IRB/IEC is responsible for verifying that written IC was obtained before each subject's participation in the trial.
FALSE The monitor is responsible. 5.18.4
(T/F) The monitor is responsible for reporting subject recruitment rates as well as providing all required reports, notifications, applications, and submissions.
FALSE The monitor must verify that the investigator is providing: Accurate reports, notifications, applications, and submissions. 5.18.4
(T/F) Once an agreement with a CRO has been finalized, all responsibilities transfer from the sponsor to the CRO.
FALSE The sponsor is still responsible for the quality and integrity of the trial data. 5.2.1
(T/F) The sponsor must only provide clinical/ study reports if a trial is completed.
FALSE The sponsor must provide reports regardless of whether the trial is completed or prematurely terminated. 5.22
(T/F) The sponsor can allocate duties and functions as the trial progresses.
FALSE The sponsor should allocate all duties and responsibilities prior to the onset of the trial. 5.7
(T/F) A sponsor must provide an audit certificate.
FALSE. The sponsor only needs to provide a certificate if applicable laws or regulations require it. 5.19.3
What standards must ADR reports comply with?
Reports must comply with the applicable regulatory requirements and ICH guidelines for Clinical Safety Data Management Definitions and Standards for Expedited Reporting. 5.17.2
(T/F) The monitor is responsible for verifying investigator's qualifications and resources and for ensuring that these remain adequate throughout the study.
TRUE 5.18.4
(T/F) The monitor is responsible for verifying that the investigator and his/her staff are adhering to the protocol and any other written agreements between the sponsor and the investigator/institution an have not delegated these functions to unauthorized individuals.
TRUE 5.18.4
(T/F) The monitor is responsible for verifying that the investigator and the investigator's trial staff are adequately informed about the trial.
TRUE 5.18.4
What is the purpose of the sponsor's SOPs?
The SOPs ensure that the trials are conducted and that the data are generated, documented and reported in compliance with the protocol, GCP, and applicable regulatory requirements. 5.1.1
What are the monitor's responsibilities regarding AEs?
The monitor must determine whether AEs are being appropriately reported within the time period mandated by GCP, the protocol, the IRB/IEC, the sponsor, regulatory requirements, and ICH reporting guidelines. 5.18.4
What pre-trial applications/ notifications/ submissions to regulatory authorities include?
~Applications ~authorizations and ~notifications All must be must be signed and dated and contain sufficient information to identify the protocol 5.10.
Who must be involved in agreements regarding financial aspects of the trial?
~Sponsor and ~investigator/institution must both be involved. 5.9
What documentation is required when an IDMC is used?
~written operating procedures and ~maintain written records of all meetings. 5.5.2
Who should document the review and follow-up of monitoring reports?
A sponsor's designated representative.
How is the agreement between the sponsor an investigator/institution finalized?
All parties should sign the protocol or an alternative document to confirm the agreement. 5.6.3
What is involved in trial design?
Clinical design involves all aspects of the trial from the initial conception through analysis and preparation of clinical trial.study report templates. 5.4.1
What must a sponsor maintain if the IRB/IEC requires modification to obtain approval/favorable opinion?
Copy of the modifications made and the date the IRB/IEC grans approval/ favorable opinion. 5.11.2
What subjects should handling and storage documentation address?
Documentation should address: ~adequate and safe receipt, ~dispensing, ~retrieval of unused product, and ~other acceptable means of disposal of unused product. 5.14.
When must the sponsor document responsibility for coordinating investigators and other participating investigators in a multi-center trial?
Documented prior to the start of the trial. 5.23.3
For how long must sponsor-specific essential documents be retained?
Documents should be retained until at least two years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marking application in an ICH region. 5.5.11
Cite examples of additional studies required when a significant formulation change is made to an investigational or comparator product.
Examples of tests required to assess the impact on the PK profile include: ~stability ~dissolution rate ~bioavailability 5.13.5
What role does an Independent Data Monitoring Committee(IDMC) play in a clinical trial?
IDMC may be used to assess the progress of a clinical trial and recommend whether to continue, modify, or stop the study. 5.5.2
What coding requirements apply to blinded trials?
In blinded trials, coding should include a: mechanism that permits rapid identification of the product(s) in case of medical emergency BUT DOES NOT result in undetectable breaks of the blinding 5.13.4
What is required if study data are transformed during processing?
It must be possible to compare the original data and observations with the processed data. 5.5.4
With what must monitors be thoroughly familiar?
Monitors must be familiar with: ~IP ~Protocol ~ICF ~Sponsor's SOPs ~GCPs ~Applicable regulatory requirements and ~Any other written information provided to subjects. 5.18.2
What type of safety and efficacy data should be available during the planning stages of the trial?
Non-clinical data and/or other clinical trial to support human exposure by the route, dosage, for the duration and in the trial population. 5.12.1
What requirements must product labeling meet?
Products must be ~Coded and labeled to protect blinding ~comply with any applicable regulatory requirements. 5.13.2
What is the purpose of a sponsor's audit.
Purpose is to evaluate trial conduct and compliance with the: ~Protocol ~SOPs ~GCPs ~applicable regulatory requirements. 5.19.1
At what stage of data handling must the sponsor ensure the existence of quality controls?
Quality control must be applied at all stages of data handling, 5.1.3
What governs the retention of sponsor-specific essential documents?
Retention must be in conformance with the applicable regulatory requirement(s) of the country(ies) where the product is approved and/or where the sponsor intends to apply for approval. 5.5.7
Who is responsible for ongoing safety evaluation of the IP? Who should they notify?
Sponsor is responsible for safety evaluations and notifying all involved parties of any concerns. 5.16
Who is responsible for supplying the investigator(s)/institution(s) with the IP(s)?
Sponsor is responsible for supplying IP AND ensuring that IRB/IEC favorable opinion is obtained prior to a shipment. 5.14.1
What document dictates monitoring procedures?
Sponsor's SOPs and trial-specific procedure determine monitoring procedures (i.e., Monitoring Plan).
(T/F) Statistically controlled sampling may be used for selecting the data to be verified through monitoring.
TRUE 5.18.3
What information regarding record retention must sponsors provide to the investigators?
Sponsors must provide written notice of records retention requirements and when records are no longer needed. 5.5.12
How should monitors be selected?
Sponsors should appoint monitors who have the scientific and/or clinical knowledge needed to monitor the trial adequately. 5.18.2
How long should product samples ideally be kept?
Stability permitting, samples should be retained either until trial data analysis is complete or in accordance with the applicable regulatory requirements, whichever represents the longer time span. 5.14.5(b)
(T/F) The sponsor must ensure that the protocol or other agreements with the investigator/institution provides direct access to source data/documents for trial-related monitoring, audits, IRB/IEC review, and regulatory inspection?
TRUE 5.15.1
(T/F) Each subject must consent, in writing, to release of records for trial-related monitoring, audits, IRB/IEC review, and regulatory inspection.
TRUE 5.15.2
To whom are supplemental CRFs provided during the conduct of a multi-center trial?
Supplemental CRFs should be provided to any investigator who are collecting additional data that is beyond the scope of the primary CRF. 5.23
What records and systems should a sponsor maintain regarding delivery and retrieval of investigational drug(s) to and from an investigator?
Systems and documentation should be maintained for: ~timely delivery ~shipment, receipt, disposition, return, and destruction ~retrieval from investigational sites 5.14
(T/F) The sponsor should obtain dated documentation of any IRB/IEC re-approvals/reevaluations as well as any withdrawals or suspensions of approval/favorable opinion.
TRUE 5.11.3
What individual serves as the primary liaison between the sponsor and investigator?
The monitor is the main line of communication.
The sponsor's written procedures determine what aspect of an audit?
The document defines: ~what to audit ~how often to audit, and the ~form and content of the audit report. 5.19.3
What must be done when trial-related duties and functions are transferred to and assumed by a CRO?
The duties and functions must be specified in writing. The sponsor retains any duties and functions that are not specified in writing. 5.2.2
Who is responsible for verifying that the investigator enrolls only eligible subjects and verifying the presence and accuracy of source data?
The monitor is responsible. 5.18.4
Who is responsible for verifying that the investigator follows the approved protocol and all approved amendments(if any)?
The monitor is responsible. 5.18.4
What must the investigator/institution agree to do when conducing the study?
The investigator/institution must agree to: ~comply with GCP, applicable regulatory requirements and protocol ~Adhere to data recording/ reporting procedures ~permit monitoring, auditing, and inspection ~retain essential documents until notified they are no longer needed. 5.6.3
What governs subject compensation?
The method and manner of compensation should comply with applicable regulatory requirements. 5.8.3
What must the monitor do to ensure that investigators can properly conduct the trial and comply with all applicable regulatory requirements?
The monitor must ensure that the investigator receives: ~the current IB, ~all documents, and ~all trial supplies needed to conduct the trial in compliance with the requirements. 5.18.4
Who must the monitor inform of CRF entry errors, omissions, or illegibility?
The monitor must inform the investigator and ensure that corrections, additions, or deletions are made, dated, explained (if necessary) and initialed by an authorized staff person. 5.18.4
What is the monitor's role if there are deviations from the protocol, SOPs, GCPs, or applicable regulatory requirements?
The monitor must inform the investigator and take action designed to prevent recurrence of the detected deviations. 5.18.4
After any site visit or trial-related communication the monitor must take the following steps?
The monitor must submit a written report to the sponsor.
What should the monitor be checking when reviewing CRF entries, source data, and other trial-related records?
The monitor must verify records documenting: ~Presence and accuracy of protocol required data and consistency with source documents ~Any dose/ treatment changes ~any AE, concomitant medications, and inter-current illnesses ~any missed visits, tests, or examinations ~all withdrawals and dropouts ~maintenance of essential documents. 5.18
What must the monitor verify in terms of the IP(s)?
The monitor must verify: ~storage times and conditions, ~sufficiency of supplies ~eligibility of subjects to receive the products(s) ~adequacy of instructions to subjects, ~control of receipt/use/return of product(s) and ~disposition of unused IP(s). 5.18.4
How should IP be packaged?
The product should be packaged to prevent: ~contamination and ~unexpected deterioration during transport and storage. 5.13.3
What must the monitor's written report to the sponsor include? (After any site visit or trial-related communication)
The report should include: ~date ~site ~monitor name ~name of the contacted individual ~a summary of the findings, deficiencies ~actions required to secure compliance. 5.18.6
Who bears the responsibility for ensuring that communication among investigators in a multi-center trial is facilitated?
The sponsor 5.23.5
Who is responsible for securing agreement from all involved parties to ensure direct access to trial-related sites, source data/documents, and reports to facilitate monitoring and auditing?
The sponsor is responsible for these arrangements. 5.1.2
What are the sponsor's responsibilities in terms of product stability and supply of product to the trial site?
The sponsor must maintain ~stability, ~provide a sufficient quantity of product(s) in the trails to reconfirm specifications, if needed, and ~maintain batch sample analysis and characteristic records. 5.14.4
What is required if the sponsor discontinues the clinical development of an IP?
The sponsor must maintain all sponsor specific essential documents for at least 2 YEARS after all discontinuations and must notify all trial investigators/ institutions and the appropriate regulatory authorities. 5.5.8
To whom must the sponsor report transfer of data ownership?
The sponsor must notify the regulatory authorities, as required by applicable regulations of any transfer of data ownership. 5.5
What must the sponsor obtain from the investigator/institution to confirm IRB/IEC review?
The sponsor must obtain: ~Name and address of the Investigator/institutions' IRB/IEC ~statement from the IRB/IEC that it uses GCP and adheres to applicable laws and regulations ~documented IRB/IEC approval/ favorable opinion ~copies of the IRB/IEC reviewed documents 5.11.1
What safety/related documents must the sponsor submit to regulatory authorities?
The sponsor must submit all safety updates and periodic reports, as required by applicable regulatory requirements. 5.17.3
What information must the sponsor provide before entering into an agreement with an investigator/institution to conduct a trial?
The sponsor must supply the protocol and an up-to-date Investigator/institution sufficient time to review the material. 5.6.2
What precautions are needed when using electronic/remote data systems?
The sponsor must: ~Verify compliance with requirements ~Maintain SOPs for system usage ~Ensure tracking of changes ~maintain system security ~control system authorization ~~backup the system ~safeguard blinding, iff applicable 5.5.3
Who and what must be notified if a trial is suspended or terminated prematurely?
The sponsor should cite the basis for the action when notify the: ~investigator/institution ~regulatory authority ~IRB/IEC 5.21
What should the sponsor consider when conducting a QA audit?
The sponsor should consider the: ~Purpose of the Audit ~Selection/ qualification of auditors ~Auditing procedures 5.19
What storage requirements must the sponsor communicate to monitors, investigators, pharmacists, and other involved personnel?
The sponsor should determine acceptable: ~Storage temperature ~storage conditions ~storage times ~reconstitution fluids and procedures ~devices for product infusion, if any. 5.13.2
What factors guide the sponsor's audit plan and procedures for trial audit?
The sponsor should determine: ~the importance of the trial to the submission, ~the number of subjects in the trial, ~the type and complexity of the trial, ~the risk level to the trial subjects and ~the unresolved problems. (5.19.3)
Who responsibilities does the sponsor have regarding manufacturing of IP?
The sponsor should ensure that the product is: ~characterized as appropriate to the stage of development of the product ~manufactured in accordance with applicable GMPs ~labeled in a way that protects the blinding 5.13.1
Who should be notified in the case of serious and unexpected ADRs?
The sponsor should expedite notification to all concerned investigator/institutions, the IRB/IECs where required and the regulatory authority(ies). 15.17
What must the sponsor obtain from the investigator/ institution to confirm IRB/IEC review?
The sponsor should obtain the name and address of the investigator/institution's IRB/IEC, a statement from the IRB/IEC that it uses GCP and adheres to applicable laws and regulations, a documented IRB/IEC approval/favorable opinion, and copies of the IRB/IEC reviewed documents, if requested. 5.11.1
What actions should the sponsor take in cases of noncompliance with the protocol, SOPs, GCPs, or other regulatory requirements?
The sponsor should remedy problems, but if they persist should terminate the investigator/institution's participation in the trial and notify the regulatory authority. 5.20
What selection criteria should the sponsor use when appointing auitors?
The sponsor should select auditors who are: ~independendent of the clinical trial/ data collection system(s) ~are qualified by training and experience. 5.19.2
Who is responsible for updating the IB?
The sponsor should update the IB as significant new information becomes available. 5.12.2
How should data be linked to the subject?
The sponsor should use an unambiguous subject identification code that links the data to the subject. 5.5.5
Who should the sponsor entrust with trial supervision, data handling and verification, statistical analysis, and preparation of the trial reports?
The sponsor should use appropriately qualified individuals. 5.5.1
A sponsor determines the appropriate extent and nature of monitoring by taking into account what aspect of the trial?
The sponsor takes into account the trial: ~objective ~purpose ~design ~complexity ~blinding ~size and ~endpoints 5.18.3
Who is responsible for selection of the investigators, including their qualifications, and coordinating committee/coordinating Investigator?
These are sponsor responsibilities. 5.6.1
When may regulatory authorities request audit reports?
They may seek audit reports on a case-by-case basis, when evidence of serious GCP noncompliance exists, or in the course of legal proceedings or investigations. 5.19.3
Under what terms must investigators in multi-center trials conduct the trial?
They must conduct the trial in compliance with the protocol and any stipulations of the IRB/IEC that grants approval/ favorable opinion. 5.23.1
What standards must the clinical trial/study reports meet in marketing applications?
They must meet the standards of the ICH GUIDELINES FOR STRUCTURE AND CONTENT OF CSRs. 5.22
What instructions should be given to the investigators involved in multi-center trials?
They should be given instructions on: ~following the protocol ~complying with a uniform set of standards for assessing findings ~completing the CRFs 5.23.4
Who is responsible for implementing and maintaining quality assurance and quality control systems with the written SOPs to ensure proper conduct of clinical trial?
This is a responsibility of the sponsor. 5.1.1
What is the purpose of trial monitoring?
Trial monitoring is designed to ensure: ~protection of subject rights and well-being ~accuracy and completeness of data ~proper trial conduct 5.18.1
(T/F) The sponsor should not supply an investigator/institution with the IP until the sponsor obtains all required documentation.
True 5.14.2
Must a sponsor's audit observations and findings be documented?
Yes, the observations and findings must be documented. 5.19.3
Do the sponsor's policies and procedures have to address the cost of treatment of subject who suffer a trail -related injury?
Yes, the sponsor's policies and procedures must address these costs in accordance with the applicable regulatory requirements. 5.8.2
Can outside consultants be designated to advise a sponsor on trial-related medical questions or problems?
Yes. Any appropriate qualified medical personnel, including outside consultants can be used in this capacity 5.3