Establishing a clinical trial site: A primer for aspiring principal investigators

Abstract

Establishing a private clinical trial site is an increasingly appealing but complex opportunity for physicians interested in becoming Principal Investigators (PIs) in FDA-regulated research. This article provides a comprehensive overview for aspiring PIs, detailing the critical requirements and best practices for launching and operating a successful site.

The topics covered include regulatory responsibilities, financial considerations, infrastructure needs, staffing roles, investigational product handling, standard operating procedures, IRB oversight, informed consent, and patient recruitment and retention strategies. Special emphasis is placed on compliance with FDA regulations and Good Clinical Practice (GCP) standards, ensuring data integrity and the protection of study participants.

The paper highlights the importance of robust infrastructure—from calibrated laboratory equipment and secure drug storage to electronic data capture systems—and the need for well-trained support staff, including clinical research coordinators and sub-investigators. The recruitment and retention of diverse participants is explored through ethical, patient-centered engagement strategies. Additionally, guidance is provided on navigating site feasibility assessments, sponsor negotiations, and the startup study process.

Drawing from the authors’ experience establishing clinical trial sites and contract research organizations, this guide offers strategic insights on building sponsor relationships, evaluating protocol feasibility, and enhancing site performance metrics. The evolving clinical trial landscape—driven by new therapeutic developments and digital technologies—demands that PIs not only meet regulatory standards but also demonstrate leadership, operational excellence, and a commitment to scientific integrity.

Highlights

• • •Setting up a clinical site requires funding, trained staff, SOPs, and proper equipment.
• • •A PI must ensure regulatory, ethical, and GCP compliance at the site.
• • •Recruitment and retention of diverse patients is crucial for site success.
• • •IRB approval and informed consent are mandatory before enrolling participants.
• • •Building sponsor trust via performance and professionalism ensures long-term viability.

Drug development is a complex process that engages many disciplines which work together to ultimately bring a compound to market and provide a significant advance in health care. In short, this process begins with drug discovery, followed by synthesis of any number of analogs, characterization of basic pharmacology profile as confirmed by in-vitro and in-vivo testing, animal toxicology, formulation, and stability testing. As daunting a task as it is to bring a compound to human trials, the trials themselves present a process that has become more complex in recent years [1]. Phase 1 trials are critical to determine the safety and tolerability of a new compound in man [2]. They also increasingly incorporate biomarker studies to confirm target engagement and optimize doses for later Phase 2 and 3 efficacy trials in patient populations [3]. These later studies also take years and crucially depend on well-designed and executed clinical trials by experienced investigators, ultimately culminating in a New Drug Application (NDA) to be reviewed by the FDA. The principal investigator plays a crucial role in drug development. Over the last two decades, the number of clinical trials has steadily increased, underscoring the need for new competent principal investigators [1,4].

A clinical trial site is more than just a physical location. It is a structured environment where investigational products are administered, data are generated, and patient safety is prioritized. Each site functions as a hub for protocol implementation, regulatory compliance, and patient engagement, and its effectiveness directly impacts trial quality and outcomes. At the center of this activity is the Principal Investigator (PI), who assumes overall responsibility for the conduct of the trial at the site. The PI ensures adherence to Good Clinical Practice (GCP), oversees the research team, manages participant recruitment and informed consent, and serves as the primary liaison with sponsors and regulatory authorities. In this capacity, the PI is both a scientific leader and a steward of ethical standards.

Principal Investigators in FDA-regulated drug trials bear the ultimate responsibility for the conduct of the study at their site. The rewards for a PI are not just monetary. It includes being on forefront of new treatments and playing an active role in bringing these treatments to market. Conducting clinical trials is not just a technical exercise, as evidenced by numerous trial failures throughout all phases of development. Even if a compound succeeds in Phases I and II it may still fail in Phase III. Trials require specialized expertise due to the complexities involved. A trial can fail for a myriad of reasons that are not necessarily related to the compound itself, from mistakes in protocol design to flawed execution of the protocol. The PI plays a critical role in helping shepherd a new treatment through trials successfully and requires a special level of expertise in cross disciplines, including knowledge of GCP, medical training, business acumen, and managerial skills. This paper provides an overview of the key US requirements and best practices for aspiring PIs based on current literature and US regulatory documents, as well as the authors’ experience in establishing three clinical trial sites and two large international Contract Research Organizations. Fig. 1 depicts an overview of the major activities essential for study start-up, beginning with a qualified investigator expressing interest in a protocol, and ultimately leading to enrollment of qualified patients.

Fig. 1.

A summary schedule of major site activities from Receipt of study protocols to study startup.

1. Regulatory responsibilities and training for principal investigators

A PI in an FDA-regulated trial must ensure the study is conducted according to the approved protocol and adheres to all applicable regulations [5]. Regulatory terms and topics from this section are defined in Table 1. Under title 21 of the Code of Federal Regulations (21 CFR) 312 (for drugs) and 812 (for devices), the PI is the accountable leader of the investigation at their site. By signing the FDA Form 1572 (for drug trials) or investigator agreement (for devices), the investigator commits to comply with FDA requirements – including personally overseeing all aspects of the trial, protecting subjects' rights and welfare, obtaining informed consent, and ensuring data integrity [6]. The PI must enroll eligible participants, and report required information including adverse events to sponsors, Institutional Review Boards (IRBs), and when necessary, regulatory bodies [7]. PIs should maintain a delegation of authority logs documenting who is performing key study tasks [8]. Ultimately, the PI's foremost duty is to protect the rights, safety, and welfare of human subjects, and ensure that patients are not exposed to unnecessary risk [7].

Table 1.

Regulatory terms relevant to a clinical trial site.

Term	Definition
21 CFR 312/812	Parts of the Code of Federal Regulations that govern FDA-regulated drug (312) and device (812) trials.
FDA Form 1572	A required document for drug trials in which the PI commits to FDA regulations and trial responsibilities.
Investigator Agreement	A signed agreement for device trials where the PI commits to FDA regulations and investigator responsibilities.
Informed Consent	A process through which participants are informed about the trial and voluntarily agree to participate.
Adverse Events	Unintended medical occurrences in participants that must be reported to sponsors, IRBs, and regulatory agencies.
Delegation of Authority Log	A document showing which study staff are delegated specific responsibilities by the PI.
Good Clinical Practice (GCP)	A set of internationally recognized ethical and scientific quality standards for designing, conducting, and reporting clinical trials.
International Council for Harmonisation (ICH)	A global body that develops GCP guidelines like ICH E6 (R2) to ensure trial quality and participant protection.
ICH E6 (R2)	A section of the ICH GCP guideline outlining responsibilities of investigators during clinical trials.
FDA Form 483	A document issued by the FDA listing significant inspection findings or protocol violations; requires written response from the PI.
Protocol Deviation	A departure from the approved study protocol, which must be documented and discussed with the sponsor.
Investigator Brochure	A document providing detailed information about the investigational product to the PI.
TransCelerate	A collaborative organization promoting standardized GCP training and clinical trial efficiency.
CITI Program/NIH Training Modules	Widely used platforms for training in GCP and human subject protection.
Human Subjects Protection	Ethical and regulatory practices ensuring the rights, safety, and welfare of trial participants.

PIs must follow Good Clinical Practice (GCP) as outlined by the International Council for Harmonisation (ICH) [9]. ICH E6 (R2) GCP Section 4 [9]. It is important that the PI avoid any violations of these regulations, which can result in the investigator receiving FDA form 483 following an FDA inspection. Form 483 lists any significant protocol violations, and the PI must promptly address in writing any such issues. The PI should carefully review any new protocol to ensure that their site can fully execute all protocol measures, particularly those which must be executed within specific time limits. PIs should document deviations from protocol by discussing them with the sponsor and putting such conversations in writing for future reference. A PI should thoroughly review the protocol before the study starts and discuss with the sponsor issues that could result in deviations, allowing a plus/minus window to be agreed upon.

Most importantly, a PI must have a high ethical standard, conduct clinical trials in concordance with the protocol, and never take shortcuts, fabricate data, or falsify data.

The PI must be a physician or otherwise appropriately qualified professional by education, training, and experience. If the PI is not a physician, then a physician must perform any medical-related protocol procedures. GCP also requires PIs to have thorough knowledge of the investigational product as detailed in the Investigator Brochure and the protocol. Most pharmaceutical sponsors require PIs and assisting research staff to complete certified GCP training and maintain it via periodic refresher courses. In fact, ICH GCP and TransCelerate guidelines promote standardized GCP training to ensure investigators are up to date on best practices [10]. Many sites use the CITI Program or NIH training modules for GCP and Human Subjects Protection [11].

The benefits of being a successful PI are many, including generous monetary compensation and working on novel potential treatments that are at the forefront of medicine. Being a successful PI requires a great deal of dedication and attention to their work. They will have to create all the infrastructure and support mechanisms necessary for a competent clinical trial site.

2. Financial considerations

An aspiring PI must face the financial realities inherent in starting up a clinical trial site which is independent of a larger institution, such as an academic center. There are considerable monetary investments that need to be made for equipment and staff. Basic equipment such as centrifuge and refrigeration storage can cost $15,000-$30,000, while equipping a full site could cost several hundred thousand dollars. An investigator might start by taking on small studies as part of their medical practice and gradually convert to full-time clinical research if they have accrued sufficient funds to take the necessary first steps. As clinical trials increase, it will be difficult for the investigator to devote adequate time to the demands of medical practice and those of clinical trials, and ethical decisions will often come up. For example, the practitioner can face a dilemma of whether to take a patient off medication on which their disease or condition is stable and enroll them in a trial where they might receive a placebo.

Running a private clinical site is also a business. Cash flow can be a problem given that sponsors often pay quarterly or after milestones, and startup costs occur up front. If a study is canceled or a site under-enrolls, revenue might not cover expenses. Robust and fair budgets must be negotiated at the outset and every allowable reimbursable cost (like extra procedures, screen failures, etc.) should be invoiced. Repeat business from sponsors who trust the site provides financial stability. A dedicated clinical trials site will be completely dependent upon study grants from pharmaceutical companies (or pass-through from CROs). Typically for Phase 2 and 3 trials, pharma will likely have a proposed budget which they present to the PI. These budgets often have ranges which consider regional differences across the country. An experienced investigator with a proven track record for the desired patient population can negotiate with the study sponsor. One also must take into consideration the costs for screening to obtain the agreed upon patient numbers to enroll, especially if a special or rare population is involved. Sometimes the sponsor will put a limit on the number of patients to be screened in relation to those enrolled. This is often a 2 to 1 ratio. The sponsor will typically pay for invoiced study procedures and tests on a pre-defined basis, for example, the site may be able to invoice the sponsor when the first quarter of patients have been completed, with subsequent invoices at pre-defined endpoints. When the site starts taking on multiple studies, the PI will want to have an accountant keep track of budgets.

3. Clinical trial site infrastructure and equipment

Creating a functional clinical trial site requires adequate infrastructure, facilities, and equipment to safely conduct study visits and manage data. Ideally, the PI should secure a suite which can be expanded later as the site grows. A location that has good access, parking and proximity to bus lines, near a hospital or ER, as well as a location that is not close to any potentially competing clinical sites. Key facility requirements are detailed in Table 2.

Table 2.

Key facility requirements for a functional clinical trial site.

Requirement	Function
Exam rooms	•Participant visits and procedures
Laboratory processing room	•For biological specimens •Equipped with a centrifuge (refrigerated)
Lockable drug storage cabinets and a locked refrigerator	•Store investigational products and biological specimens within the temperature range specified by the sponsor. •A minus 70- or 80-degree freezer is required for many specimens. •Area must be access-controlled, restricted only to authorized personnel. •Calibrated pharmaceutical grade refrigerator with continuous temperature monitoring and alarm systems, plus backup power or contingency plans for outages is highly desirable. •Controlled substances require even tighter security: per 21 CFR 312.69, investigational drugs must be stored in a securely locked and well-constructed cabinet with limited access.
Reliable utilities for climate control and secure internet/phone connectivity	•Many modern trials use cloud-based EDC and eSource, so sites must have secure networks and up-to-date browsers to interface with these systems. •Infrastructure for data management should comply with 21 CFR Part 11 and privacy laws, ensuring secure handling of electronic records. •Sites also typically utilize a Clinical Trial Management System (CTMS) or at least spreadsheets to track visits, enrollment, and billing and payment milestones.
Calibration records	•Sites should keep calibration records and perform routine checks on instruments used for study measurements
Supplies for sample shipping	•International Air Transport Association (IATA)-compliant packaging, dry ice if needed for frozen samples
Personal protective equipment (PPE)	•Protection for staff processing biohazards.
Basic emergency supplies	• As a clinical trials site is also a medical office, basic emergency supplies should be stocked and expiration dates checked regularly. • A suggested list includes: o Basic Airway and Breathing Support: Bag-valve mask; oxygen tank with regulator o Circulatory Support: Automated external defibrillator; pulse oximeter; glucose monitor o Emergency Medications: Epi-pen; Benadryl (PO and IM); dextrose 50 % syringe; albuterol inhaler

4. Investigational drug storage and handling requirements

Proper handling of investigational drugs (and devices) is a fundamental part of running a competent clinical trial site. According to ICH GCP 4.6, the investigator (often via a pharmacist or designated staff) should maintain logs tracking delivery, inventory, use by each subject, and disposal or return of unused stock to the sponsor.

Daily temperature checks are expected, and any out-of-range temperature deviation must be reported and addressed according to directions given by the sponsor. Investigational drugs should also be stored separately from standard clinic medications to prevent mix-ups, with labels indicating “For Investigational Use Only.” If patients take doses at home (as in outpatient trials), the site should educate them on proper storage and may use tools like drug diaries or medication counts to verify adherence. At the study end or when a participant's participation ends, the site either returns unused IP to the sponsor or destroys it per sponsor instruction.

5. Staffing roles and qualifications at a trial site

Conducting clinical trials is a team effort that requires several specialized roles to assist the PI. Often staff are recruited from other sites for various reasons, including reduced commute, higher pay, and new opportunities for advancement. An experienced and reliable clinical research coordinator (CRC) performs crucial day-to-day study operations at the site as well as a myriad of other activities essential to study conduct and should be among the first staff employed. Additional key staff members are summarized in Table 3.

Table 3.

Key staff members at a clinical trial site.

Staff	Function
Principal Investigator (PI)	•The accountable leader of a clinical trial at their site, responsible for ensuring the study follows the protocol and regulatory requirements.
Sub-Investigator (Sub-I)	•Key professionals (i.e., psychometricians for rating scales or physicians who are board certified in specialties essential for study conduct) on the research team who perform important trial procedures or evaluations under the PI's supervision. •Listed on Form FDA 1572 as “sub-investigators”, though the PI retains primary responsibility. •Can be a co-investigator specializing in a certain aspect of the study. •Must also have appropriate qualifications and GCP training.
Clinical Research Coordinator (CRC)	•Performs crucial day-to-day study operations at the site. •Manages logistics and data collection for the trial. •Acts as a link between PI and trial participants. •Duties include screening and recruiting participants, explaining the study and obtaining informed consent (delegated by the PI), scheduling study visits, and ensuring each visit's procedures are completed according to the study protocol. •Maintains study documentation – keeps the regulatory binders, source documents, and case report forms up to date. •Performs data entry into EDC systems and responds to data queries. •Handles investigational product dispensing, accountability and shipping lab specimens. •Most CRCs have a healthcare or science background (nursing, biology, etc.) with a minimum of a bachelor's degree. •Must be well-versed in GCP and often obtain or are working towards certification (e.g. Association of Clinical Research Professionals (ACRP) or Society of Clinical Research Associates (SOCRA) certification for research coordinators).
Clinical Research Associate (CRA)	•Monitor from sponsor or Contract Research Organization (CRO) assigned to oversee the site.
Regulatory Coordinator/Document Specialist	•Many sites have dedicated regulatory coordinators who manage regulatory binder and correspondence with IRBs and sponsors. •Oversees IRB approvals, protocol amendments, training logs, delegation logs, CVs/licenses, and FDA forms.
Additional Roles	•Depending on trial complexity, site may employ or contract a Research Pharmacist, Laboratory Technician, and Recruitment Specialist. •Data managers or quality assurance (QA) personnel might also be involved in reviewing ongoing entered data for errors and to ensure readiness for FDA audits.

6. Standard operating procedures (SOPs)

SOPs should be in place for all important activities of the clinical site, and sponsors will often ask to review certain SOPs to make sure that the site is compliant with best practices. SOPs can be created and modified from existing standards in the field as well as through input and refinement by consultants that have written these routinely. While not a comprehensive list, recommended SOPs are listed in Table 4.

Table 4.

Recommended SOPs for important clinical site activities.

Study documents/source documents
IRB submission
Procedure for obtaining written informed consent
Handling of investigational medication
Health Insurance Portability and Accountability Act (HIPPA) compliance
Use of electronic signatures
Emergency medical procedures
Equipment calibration
QA audits
Regulatory inspections
Corrective actions
Protocol deviations
Staff training
Job descriptions

7. IRB oversight and informed consent procedures

Any FDA-regulated trial involving human subjects must be reviewed and approved by an IRB (or Ethics Committee). The PI is responsible for obtaining IRB approval of the research protocol, informed consent form, and recruitment materials prior to initiating the study or enrolling any participants. Additionally, the PI must ensure that continuing review is conducted at least annually (or as stipulated) and that no changes to the protocol are implemented without prior IRB approval, except when necessary to eliminate immediate hazards to subjects, per 21 CFR 56. Protocol amendments, consent form revisions, and any new advertising must be submitted to the IRB for approval. Many trials now use central IRBs to streamline the process, and this typically results in faster study start up. The PI must promptly report any unanticipated problems or serious adverse events to the IRB, as well as any protocol deviations that might affect safety or rights.

Before any study-specific procedures are conducted, each participant (or their legally authorized representative) must give informed consent. The PI or a delegated qualified person (often the CRC or Sub-I) should conduct a consent discussion in the language the subject can understand, covering the nature of the research, duration, required procedures, potential risks and benefits, any compensation, protection of confidentiality, and the subject's rights, including the right to withdraw at any time, per 21 CFR 50.25. The subject should have ample time to read the consent form and ask questions. The process must use a translator or translated consent form if the participant is not fluent in English and include an impartial witness for consent if the participant is illiterate. Any new information that arises during the trial (for instance, new risks or changes in the protocol) must be communicated to participants, often via a revised consent form.

All protocol deviations should be documented and reported to the IRB (immediately if it affects safety, or in summary at continuing review if minor). If the study involves any Certificates of Confidentiality or specific privacy provisions (like HIPAA authorizations in the US) these need to be handled alongside consent. By ensuring rigorous IRB oversight and a thorough informed consent process, the PI builds public trust in research.

8. Patient recruitment strategies and retention in trials

Enrolling and retaining participants is often one of the biggest challenges in clinical research. In one analysis from a sponsor's database, it was found that approximately 80 % of participant recruitment was accomplished by 20 % of sites [12]. Thus, a site that can effectively enroll and retain study subjects becomes an asset for the sponsor. Study participants must be commended for their willingness to take part in investigational studies, but the motivation to do so is not always driven by an altruistic drive to help humanity. In a review of literature by Knapp et al. (2025) [13], the most common reasons that facilitate patient participation were altruism, personal benefit, and trust.

Successful sites develop recruitment plans at study outset, which may include strategies such as.

• -Creating IRB-approved advertisements (flyers, newspaper ads, radio spots, social media posts). Digital strategies have recently become prevalent including targeted social media campaigns. For large, multisite studies, sponsors may provide advertising on a regional or national level via a website or online advertisements, 1–800 numbers, TV commercials or other media for recruiting purposes which would funnel respondents to the nearest clinical site to evaluate whether they qualify for the study. Outreach can be conducted by a contracted third party or preferably, the site staff.
• -Community outreach - e.g. giving informational talks at community centers, patient advocacy groups, or health fairs. The site might partner with local physicians for referrals. However, we have found this strategy to be of limited value, since physicians also value their patients and might be reluctant to lose track of them.
• -For PIs concurrently running a private practice, clinical trial recruitment can occur from direct interaction between the PI/staff and a potential participant.

During prescreening calls or visits, a CRC assesses whether the person is likely to meet protocol inclusion/exclusion criteria before scheduling an official screening visit. Throughout, it is important that no coercion is used – participation must be voluntary, and unrealistic expectations should not be given. Setting proper expectations from the start (about time commitment, possible placebo, etc.) aids retention later.

Sponsors usually allocate a target number of participants for each site. A high-performing site will aim not only to hit the numeric target but also to enroll a population that reflects diversity goals (e.g. diversity in age, sex, race as appropriate for the disease). Sites are encouraged to have a plan for enrolling diverse participants, which could involve outreach to different communities or addressing barriers like transportation and language.

Successful sites adopt a patient-centered approach, treating participants with respect, providing clear instructions, and minimizing inconvenience [14]. Common retention techniques include regular follow-up calls or messages to remind participants of upcoming visits, sending appointment reminders (phone calls, texts) and being somewhat flexible in scheduling when possible [15]. Many trials reimburse participants for travel or provide stipends for time; ensuring that these reimbursements are handled smoothly can improve satisfaction. Some sites equip their waiting rooms with amenities (refreshments, Wi-Fi, television, etc.) to make visits more comfortable.

It is also vitally important to maintain contact with participants between visits. Educating participants on the importance of their role and the contribution they are making to medical research can bolster their commitment. Having a consistent coordinator or point of contact who knows the participant by name and checks on their well-being fosters the patient-site relationship.

Despite the best efforts, some participants will consider withdrawing from a study. The site should identify and address concerns early. If scheduling is a problem, it may be possible to offer flexible visit options or use home health nurses for certain visits. By prioritizing the participant experience, sites not only meet enrollment numbers but also ensure the data collected is complete and meaningful, as dropouts can undermine study validity.

9. Site feasibility and study startup process

Beginning a study can be challenging. Not all the above elements of a competent clinical trial site are likely to be fully in place when the aspiring PI begins to take on a first trial. Site equipment will be at the minimum necessary for the anticipated first study, and the few staff on hand will serve multiple roles until more studies arrive and finances allow expansion. The first study may come from pharmaceutical contacts that the PI had established during their training, career or from contacts at professional meetings. The PI can also indicate interest in taking on new studies by registering on the websites of CROs, which increasingly screen and select clinical sites [16].

When a sponsor or CRO is considering a site for a trial, they typically begin with a site feasibility questionnaire. The PI should answer any inquiries thoroughly and honestly – emphasizing strengths but also acknowledging any limitations. If the initial feasibility looks promising, the sponsor will set up a pre-study visit, tour the facility to check for adequate space and equipment, interview the PI and staff about their plans to recruit and conduct the trial, and review regulatory binders or SOPs [17]. This is the site's chance to impress the sponsor with their preparedness. A novice investigator might be wise to build a track record by first taking on studies that are relatively easy to enroll, such as vaccine studies or Phase 4 marketing studies.

Early in this process, the site will sign a Confidential Disclosure Agreement before receiving the full protocol. Two key documents must be agreed upon: the Clinical Trial Agreement (CTA) and the budget. The CTA is the legal contract between the site and the sponsor (or CRO) that outlines responsibilities, indemnification, publication rights, and payment terms. Sites should carefully review the sponsor's proposed per-patient budget and the schedule of payments and negotiate if necessary.

Per ICH GCP, there is a list of documents to gather before trial start, which will be filed in the site's Investigator Site File. These include.

• -Investigator qualifications: an updated CV for the PI, medical license verification, proof of GCP training certification, and any other required training (e.g. IATA certification if shipping hazardous samples).
• -Form FDA 1572: signed by the PI, listing the IRB, sub-investigators, site address, lab, and pharmacy. Similarly, financial disclosure forms (FDA Form 3455) need to be completed by the PI and any sub-Is per 21 CFR Part 54.
• -A copy of the IRB approval letter for the protocol and consent, and any recruitment materials.
• -If a local laboratory will be used for any study labs, the lab's Clinical Laboratory Improvement Amendments (CLIA) certification.

Gathering and submitting these documents can be labor-intensive. Many sponsors now use electronic systems or secure portals to exchange regulatory documents, and e-signatures are widely accepted. Utilizing an eRegulatory system can help track which documents are completed and which are outstanding.

Once the above are completed, the sponsor will schedule a Site Initiation Visit (SIV), typically conducted by a CRA. This can be on-site or remote. During the SIV, the CRA will review the protocol in detail with the site team, ensure all training is complete, verify that all essential documents are in order, confirm investigational product has been shipped and stored correctly, and verify lab kits and equipment are on hand. The PI, sub-Is, CRCs, and other key staff should attend the SIV to demonstrate they understand the protocol. After a successful SIV, the sponsor will issue an activation notice confirming the site may begin recruiting.

From the site's perspective, study startup is completed when the first patient is enrolled (sometimes called First Patient In, FPI). An electronic system to control access [EDC, Interactive Web Response System (IWRS) randomization system, central lab portal, etc.] must be set up for relevant staff. A common goal is to go from site selection to initiation in a couple of months. As a site grows, it is important to collect and evaluate common performance and risk metrics [18,19]. At a minimum these should include metrics related to recruitment, the number of screened to enrolled subjects, percentage of enrolled who complete the study, and number of protocol deviations [20].

10. Concluding remarks

This is a very exciting time for launching a clinical trials site. There will be continued and accelerated new drug discoveries, driven by investor capital, market demand and artificial intelligence, creating an environment in which successful PIs and sites will flourish.

Beyond the many technical aspects of starting and running a competent clinical trial site, demonstrating scientific and medical expertise, as well as establishing credibility, remain core tenants for success. Recruiting a team of expert trialists with deep pedigrees that engage sponsors early with advice and guidance helps foster relationships that eventually lead to new business. A thoughtful review of protocol design and eligibility criteria can often reveal meaningful comments to share with the sponsor and display the PI's proficiency. Further recognition by the pharma industry can result from presenting posters or papers at major medical meetings, publishing study results (or anonymized aspects of a given study if results are not made public), and writing review articles and white papers on diseases and treatment topics to demonstrate a depth of knowledge. Such measures do not have immediate payback but reap future rewards as the reputation of the investigator grows within the industry.

Being a successful Principal Investigator and running a thriving clinical trial site requires a blend of scientific expertise, leadership, regulatory diligence, operational acumen, and patient-centric focus. PIs must navigate FDA regulations and GCP responsibilities, ensuring they and their teams are always well-trained and compliant. The important differentiator for PIs is execution: effective recruitment and retention of participants, smooth study startup, and agile problem-solving when challenges arise. Clinical research is a demanding field, but with the right preparation, a Principal Investigator can become a valuable contributor to drug development – advancing medicine and science while safeguarding participants, which is the ultimate goal of every FDA-regulated trial.

CRediT authorship contribution statement

John J. Sramek: Writing – review & editing, Writing – original draft, Conceptualization. Modesto S. Carrillo: Writing – review & editing, Writing – original draft, Conceptualization. Neal R. Cutler: Writing – review & editing, Writing – original draft, Conceptualization.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

No data was used for the research described in the article.