#10: Investigator Responsibilities – Protecting the Rights, Safety, & Welfare of Study Subjects

October 26, 2016

In October 2009, the FDA issued a guidance document regarding its expectations for investigators during the conduct of clinical investigations.The guidance, entitled Investigator Responsibilities—Protecting the Rights, Safety, and Welfare of Study Subjects, “provides an overview of the responsibilities of a person who conducts a clinical investigation of a drug, biological product, or medical device (an investigator as defined in 21 CFR 312.3(b) and 21 CFR 812.3(i)).”

This guidance is important because it helps clarify what the FDA is looking for and helps investigators to better “meet their responsibilities with respect to protecting human subjects and ensuring the integrity of the data from clinical investigations.”

Supervision of the Conduct of a Clinical Investigation

Throughout clinical trials, is common for investigators to delegate certain tasks to other people involved in the study.  However, the investigator must keep in mind that they are still responsible for supervising the individuals performing these tasks.  Accordingly, FDA states that any regulatory violations resulting from insufficient supervision falls back on the investigator in charge of the study.

To determine the adequacy of an investigator’s supervision, the FDA focuses on four major areas, which include:

  1. Whether individuals to whom tasks were delegated are qualified to perform such tasks
  2. Whether study staff received adequate training on how to conduct the delegated tasks and were provided with an adequate understanding of the study
  3. Whether there was adequate supervision and involvement in the ongoing conduct of the study
  4. Whether there was adequate supervision or oversight of any third parties involved in the conduct of a study to the extent such supervision or oversight was reasonably possible.

Appropriate Delegation of Study-Related Tasks

When delegating tasks, the investigator should ensure that the individual is qualified to perform the job.  In order to determine if the individual is qualified, the investigator should take into account his or her education, training, and experience.  If any special licensing or certification requirements exist, it is important that they are taken into account when considering the delegation of tasks as well.

The investigator is responsible for maintaining a list of the appropriately qualified people that have been assigned to complete significant trial-related tasks.  This list should include a description of the delegated task, identify the training that the individual assigned to perform the task has received, and identify the dates of involvement in the study.

Adequate Training

In its guidance document, FDA states that the investigator should ensure that staff:

  • “Are familiar with the purpose of the study and the protocol
  • Have an adequate understanding of the specific details of the protocol and attributes of the investigational product needed to perform their assigned tasks
  • Are aware of regulatory requirements and acceptable standards for the conduct of clinical trials and the protection of human subjects
  • Are competent to perform or have been trained to perform the tasks they are delegated
  • Are informed of any pertinent changes during the conduct of the trial and receive additional training as appropriate”

Adequate Supervision of the Conduct of an Ongoing Clinical Trial

Each study site should have a distinct individual who is identified as the investigator and who has supervisory responsibility for the site.  Some sites may also have a subinvestigator who reports directly to the investigator.  The primary supervisory responsibility for the site should not be delegated to the subinvestigator.

It is important that the investigator has enough time to properly conduct and supervise the clinical trial.  The supervision that is provided may vary from trial to trial, and should be appropriate to the staff, nature of the trial, and the subject population.  According to FDA, “the following factors may affect the ability of an investigator to provide adequate supervision of the conduct of an ongoing clinical trial at the investigator’s site:

  • Inexperienced study staff
  • Demanding workload for study staff
  • Complex clinical trials (e.g., many observations, large amounts of data collected)
  • Large number of subjects enrolled at a site
  • A subject population that is seriously ill
  • Conducting multiple studies concurrently
  • Conducting a study from a remote (e.g., off-site) location
  • Conducting a study at multiple sites under the oversight of a single investigator, particularly where those sites are not in close proximity”

The investigator should have a plan for the supervision and oversight of the study, which should apply to everyone involved in the trial – even the most highly qualified and experienced individuals.

Investigator’s Responsibilities for Oversight of Other Parties Involved in the Conduct of a Clinical Trial

“Staff involved directly in the conduct of a clinical investigation may include individuals who are not in the direct employ of the investigator.”  Although these individuals are not directly employed by the investigator, the investigator is still responsible for supervising the tasks performed by these individuals.

Sometimes, there are certain aspects of a study that are performed by parties not directly involved in patient care or contact and not under the direct control of the investigator.  In these circumstances, the FDA states that “the sponsor is responsible for ensuring that these parties are competent to fulfill and are fulfilling their responsibilities to the study.”

There are also a number of situations in which field clinical engineers (device sponsor employees) have been involved in certain investigational device procedures by providing technical assistance to the medical device investigator.  According to the guidance document, “the field clinical engineer should be supervised by the investigator because the field clinical engineer’s presence or activities may have the potential to bias the outcome of studies, may affect the quality of research data, and/or may compromise the rights and welfare of human subjects.”

Protecting the Rights, Safety & Welfare of Study Subjects

It is the investigator’s responsibility to protect the rights, safety, and welfare of subjects during a clinical trial.  This includes:

  • “Providing reasonable medical care for study subjects for medical problems arising during participation in the trial that are, or could be, related to the study intervention
  • Providing reasonable access to needed medical care, either by the investigator or by another identified, qualified individual (e.g., when the investigator is unavailable, when specialized care is needed)
  • Adhering to the protocol so that study subjects are not exposed to unreasonable risks”

Reasonable Medical Care Necessitated by Participation in a Clinical Trial

During a subject’s participation in a clinical trial, it is the investigator’s responsibility to ensure that reasonable medical care is provided for any adverse events related to the subject’s participation in the trial.  If the investigator does not personally possess the expertise necessary to provide appropriate medical care, it is their responsibility to make sure that the subject is able to obtain the necessary care from a qualified practitioner.

In addition, “the investigator should also inform a subject when medical care is needed for conditions or illnesses unrelated to the study intervention or the disease or condition under study when such condition or illness is readily apparent or identified through the screening procedures and eligibility criteria for the study.”

Reasonable Access to Medical Care

The investigator should be easily accessible to subjects throughout the trial for medical care related to participation in the trial.  This is especially important when the trial involves exposure to a drug that has significant toxicity or abuse potential.  “During any period of unavailability, the investigator should delegate responsibility for medical care of study subjects to a specific qualified physician who will be readily available to subjects during that time (in the manner a physician would delegate responsibility for care in clinical practice).”  Furthermore, if the investigator is not a physician, there should be adequate provisions in place for any necessary medical care that the investigator is not qualified to provide.

Protocol Violations that Present Unreasonable Risks

In certain circumstances, failure to comply with the study’s protocol could be considered a failure to protect the rights, safety, and welfare of subjects because the non-compliance exposes subjects to unreasonable risks.  FDA recommends that investigators should do everything they can to minimize such risks, which can be done by adhering closely to the study protocol.

Clinical trials can take a number of twists and turns and it is not uncommon for the unexpected to occur.  For this reason, ensuring and maintaining compliance with all of FDA’s regulations can be difficult.  That is why where are here to help.  We have a proven track record of helping our clients comply with all relevant requirements and we can do the same for you.  To learn more about our clinical quality and GCP services, contact us today.


Post-COVID Challenges with Investigation Backlog: Are You Ready for the Inevitable?

In early 2020, while COVID-19 was wreaking havoc on public health and safety, the FDA took the unprecedented step of postponing domestic and foreign inspections. The FDA’s risk-based inspection...

Project Management and a Successful Reduction in Investigations Backlog: The Beauty and the Beast

Many of us have been faced with this beast that needs taming: a regulatory agency has conducted an inspection of your facility. Their observation is that the backlog of investigations at your site is...

September 30, 2015

FDA Releases Draft Guidance Regarding the Use of Investigational Tobacco Products

Currently, there are no regulations specifically regarding investigational tobacco products. As such, at this time they are not exempt from requirements stated in the FD&C Act. Last week, FDA...