Sponsor Obligations and Quality Management

Part of Good Clinical Practice (GCP) — ICH E6(R3): Roles and Responsibilities in Clinical Trials.

About 7 minutes. Free, in your language, no account needed.

Why this matters

Site staff often treat sponsor obligations as somebody else's problem. The sponsor decides which protocol deviations count as important, sets the quality approach the site works inside, and oversees every service provider that reaches your site. When you know what the sponsor owes you, you can ask for it.

Who the sponsor is

The ICH E6(R3) Glossary defines the sponsor as "An individual, company, institution or organization that takes responsibility for the initiation, management and arrangement of the financing of a clinical trial." A trial may have one or several sponsors. Where a documented agreement does not say which sponsor holds a given responsibility, that responsibility lies with all sponsors.

A sponsor-investigator is one person who both initiates and conducts a trial. That person holds both sets of obligations.

Allocation, agreements and transferred activities

Before trial activities begin, the sponsor determines the roles and allocates trial-related activities. The sponsor must use appropriately qualified individuals, for example biostatisticians, physicians, data scientists, auditors and monitors, and must have medical personnel readily available to advise on trial-related medical questions.

Agreements with investigators, institutions, service providers and committees must be documented before the activities begin, and updated when the transferred activities change significantly. E6(R3) then states the rule that decides most disputes:

"The sponsor's trial-related activities that are not specifically transferred to and assumed by a service provider are retained by the sponsor."

And, on responsibility rather than activity:

"A sponsor may transfer any or all of the sponsor's trial-related activities to a service provider in accordance with applicable regulatory requirements; however, the ultimate responsibility for the sponsor's trial-related activities, including protection of participants' rights, safety and well-being and reliability of the trial data, resides with the sponsor."

E6(R3) adds two practical duties. Any service provider used must implement appropriate quality management and must report to the sponsor any incident that might affect participant safety or trial results. Where the sponsor identifies a service provider to support an activity that belongs to the investigator, the responsibility for that activity still remains with the investigator.

Sponsor oversight

Section 3.9 sets out what oversight means in practice.

• The sponsor ensures the design, the conduct, the processes and the data are of sufficient quality for reliable results, participant safety and appropriate decision making.
• Oversight is proportionate. "The range and extent of oversight measures should be fit for purpose and tailored to the complexity of and risks associated with the trial. The selection and oversight of investigators and service providers are fundamental features of the oversight process."
• The sponsor ensures appropriate and timely escalation and follow-up of issues.
• The sponsor may establish an independent data monitoring committee (IDMC) to assess progress, safety and efficacy endpoints at intervals, and to recommend whether to continue, modify or stop the trial.
• Where an endpoint adjudication committee is used, it should typically be blinded to treatment assignment "regardless of whether the trial itself is conducted in a blinded manner".
• Any committee that could affect participant safety or the reliability of results needs relevant expertise, managed conflicts of interest, written operating procedures such as charters, and documented decisions.

Important protocol deviations

This is a term of art and the sponsor owns it. E6(R3) section 3.9.3 states that the sponsor "should determine necessary trial-specific criteria for classifying protocol deviations as important", and defines them as:

"a subset of protocol deviations that may significantly impact the completeness, accuracy and/or reliability of the trial data or that may significantly affect a participant's rights, safety or well-being."

At the site, the investigator documents all protocol deviations. For those deemed important, the investigator explains them and implements measures to prevent recurrence. The classification criteria should be in the protocol or monitoring plan. If your site cannot find them, ask the sponsor.

Quality management and quality by design

Section 3.10 is the headline change from the previous revision. The sponsor implements a system to manage quality "throughout all stages of the trial process". The sponsor adopts "a proportionate and risk-based approach to quality management, which involves incorporating quality into the design of the clinical trial (i.e., quality by design) and identifying those factors that are likely to have a meaningful impact on participants' rights, safety and well-being and the reliability of the results (i.e., critical to quality factors as described in ICH E8(R1))."

The sponsor must describe the quality management approach in the clinical trial report.

Quality management is not the same as quality assurance and quality control, which sit in section 3.11. Quality assurance includes risk-based strategies to identify potential or actual causes of serious noncompliance so that corrective and preventive actions can follow. Quality control is applied using a risk-based approach at each stage of data handling. E6(R3) states plainly that "monitoring and data management processes are the main quality control activities."

Quality by design is also written into trial design. Section 3.1 requires sponsors to incorporate quality into the design by identifying critical to quality factors and managing risks to them, to consider input from interested parties such as healthcare professionals and patients, and to avoid unnecessary complexity. The sponsor "should not place unnecessary burden on participants and investigators."

In practice

Description. ABC Pharmaceuticals transfers central laboratory services and courier logistics to a service provider. Samples from Dr. Sarah's site arrive at the laboratory outside the required temperature range three times in six weeks. The service provider re-runs what it can and does not tell the sponsor, because its contract measures it on turnaround time.

Ethical dilemma. The affected results support a safety assessment. If nobody reports the excursions, the sponsor cannot judge the impact on participant safety or on data reliability, and the site is blamed for missing results.

Resolution. Under E6(R3), the service provider must implement appropriate quality management and report to the sponsor incidents that might affect participant safety or trial results. Transferring the activity did not transfer the responsibility: it resides with ABC Pharmaceuticals. The sponsor escalates, assesses whether the affected results are reliable, decides whether the excursions meet its criteria for important protocol deviations, and revises the courier arrangement. Dr. Sarah's site documents the excursions in its own records.

A transferred activity is still the sponsor's responsibility.

Key takeaways

• Transfer moves the activity, not the responsibility: any sponsor activity not specifically transferred to and assumed by a service provider is retained by the sponsor.
• The sponsor defines the trial-specific criteria for classifying a protocol deviation as important, and important deviations are those that may significantly affect data reliability or participant rights, safety or well-being.
• Sponsor oversight must be fit for purpose and tailored to the complexity and risks of the trial, and the selection and oversight of investigators and service providers are fundamental to it.
• Quality management under E6(R3) means designing quality in, using a proportionate risk-based approach and identifying critical to quality factors as described in ICH E8(R1).
• The sponsor must describe the quality management approach in the clinical trial report.
• Monitoring and data management are the main quality control activities, and they are distinct from quality assurance, which targets the causes of serious noncompliance.