Clinical trials take place all over the world, in hospitals, universities, doctors' offices, and community health clinics. They can take years to plan and execute, and, as we have mentioned in past articles, many organizations and individuals come into play along the way. The study sponsor is the party funding the research, so research can generally be divided into 2 groups, according to the type of sponsor. Trials sponsored by pharmaceutical biotech or medical device companies are called industry-sponsored trials. In an investigator-sponsored trial (IST), the sponsor is not a commercial entity, but rather a clinical investigator, or, in the case of retinal clinical studies, a retinal specialist. These trials provide pivotal contributions to clinical research and development and to advancing medical and scientific knowledge.

Who is an investigator sponsor?

A study sponsor is “a person who takes responsibility for and initiates a clinical investigation.”1 In an IST, the sponsor is “an individual who both initiates and conducts an investigation and under whose immediate direction the investigational drug is administered or dispensed.”1 The criterion is that the investigator-sponsor plans, designs, and conducts the investigation and must comply with the requirements of both the investigator and the sponsor. Investigator-sponsors are in a unique position to participate in protocol development and receive the satisfaction of being a part of cutting-edge research.2

ISTs

Clinical trials proposed upon the initiative of a retinal specialist without a company taking the role of a sponsor are called ISTs. These trials are also known as investigatorinitiated trials or investigator-initiated studies.

Clinical trials conducted during investigational new drug (IND) phase (ie, pre-US Food and Drug Administration [FDA] approval) are intended to support the approval of a new product and, as a result, do not determine all the potential uses for a medication. Generally, IND clinical studies are very strict with respect to the patient population included, so subgroups or outliers are typically not included. Also, these studies typically use a single active control or placebo control, so comparisons to alternative treatments are not included. Although these IND clinical trials may help to prove a drug's efficacy and provide data to obtain marketing approval,2 a real picture of how the drug is used in a real-world setting is obtained once the drug is used more globally and in a wider population of patients. Studies performed by retina specialists on their own accord can help to create a more complete understanding of a drug's full range of capabilities. ISTs provide an opportunity to expand product knowledge, often identifying new ways of using existing treatments.2 The uses of these trials include exploring use of a marketed drug for new indications, in new populations, or with new dosage regiments; evaluating biomarkers for potential use in diagnostic tests or treatment management; clarifying safety and/or effectiveness information; observational studies; independent research on disease states; and fostering scientific exchange and collaboration. Scientific rationale, quality of the study design, endpoints, need for the study (unmet medical needs), formulation, statistics, and budget are all valid criteria for study approval.

Although pharmaceutical or commercial entities may not sponsor ISTs from the regulatory perspective, they can provide support in the form of test articles, grants, consultation for strategic input, and other services. These studies may still be of use to the commercial entity, so they may find the study worthy of support. The data may add to a company's safety profile for the product and/or lend academic credibility to the product research. Additionally, greater weight may be attached to nonindustry sources of data,2 and support of ISTs demonstrates a company's good faith and belief in its product. Many companies have websites dedicated to ISTs and provide information pertaining to support by way of funding and/or supplying a drug, depending on the type of research. Investigators can contact the industry entity to request use of the product in the study and/or to ask for funding in the form of research grants. ISTs can also be funded by academic institutions or the government.2 It is important to keep in mind, however, that the trial must be initiated by the retinal specialist and not by the company.2 This means that the retina specialist generates the research proposal independent from commercial entities.

ISTs often benefit from retinal specialists' expertise and experience. Still, these trials are held to the same standards and regulations as industry-sponsored trials, so they can be large undertakings. It is important that the investigator-sponsor initiating the study is prepared to take on the multiple responsibilities that might normally be divided up among other investigators.

RESPONSIBILITIES OF THE INVESTIGATOR-SPONSOR

Should the research proposal by an investigator be accepted, the investigator then serves as both the study sponsor and the investigator and assumes responsibility for initiating and conducting the study, directing the administration of study drug when applicable, ensuring compliance with local laws and regulatory requirements, and the analysis and communication of the study results, including manuscript publication. In particular, the investigator-sponsor is held accountable for ensuring that all pertinent regulations and guidelines are adhered to. These include both the FDA's Code of Federal Regulations and the International Conference on Harmonization's Guideline for Good Clinical Practice.3 Although normally the industry-sponsor or a contract research organization would take on the responsibilities of creating a well-designed, ethical protocol and designing case report forms, in an IST these tasks lie in the hands of the investigator-sponsor.3 Investigator-sponsors also need to select qualified investigators, sites, and monitors, and ensure that the study sites obtain the appropriate institutional review board approval, in addition to ensuring that the study is conducted according to protocol and good clinical practice. Product accountability will also fall under the investigator-sponsors' duties, so he or she must ensure that the study drug or device is located in a safe place with limited access, as in any clinical trial.

CONCLUSIONS

Improved patient-oriented research in the form of ISTs is monumental in broadening the understanding of the potential uses of a medication. Utilizing innovative clinical trials beyond those that are industry sponsored allows expanded product knowledge and the ability to identify new ways to use existing treatments.

Aron Shapiro is Vice President of Retina at Ora Inc., in Andover, MA.

  1. CFR - Code of Federal Regulations Title 21, Volume 5, Section 312.3. http://www. accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.3. Accessed November 20, 2013.
  2. Suvarna V. Investigator initiated trials (IITs). Perspect Clin Res. 2012;3(4):119-121.
  3. Society of Clinical Research Associates: Monitoring Investigator-Initiated Trials: The Role of the Institution. http://www.socra.org/pdf/2008FebSoCRASource.pdf. Accessed November 20, 2013.