Developing clinical research in a clinical hepatology practice

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Abbreviations

CRO

contract research organization

IRB

institutional review board

Academic medicine, encompassing excellence in teaching, research, and clinical activity, is no longer isolated to the traditional university medical center.1 Many clinical hepatologists have successfully incorporated clinical research into their practice. Although not without its significant challenges, it is possible to develop a clinical research program in your practice with the right planning and support.

Clinical research in the clinical practice environment has become increasingly common in liver disease therapeutic development. An explosion in therapeutic advances and available therapies for patients with liver disease has led to parallel growth in clinical trials along with the need for sponsoring pharmaceutical companies to rapidly and efficiently enroll subjects.2, 3 Clinical practices often have an advantage in start‐up time and subject enrollment when compared with traditional university medical centers.4 There is frequently a short window to be competitive for site selection, and factors such as lack of access to a central institutional review board (IRB) and a more prolonged contract and budget negotiation process in a university setting often place them at a disadvantage compared with nonuniversity clinical practices. Therefore, a private practice or smaller nonuniversity‐based environment may have several advantages in the arena of industry‐sponsored clinical trials (Table 1). Furthermore, a clinical research program can bring recognition to a practice and increase referrals by offering treatments not otherwise available in the community.3, 4 Clinical research can serve as an additional source of revenue for a practice. Meaningful participation in research can be intellectually rewarding, add variety to a practice, and provide networking opportunities at investigator meetings or national conferences. With increased experience as a principal investigator, opportunities for research and the reputation of one's institution can increase in a virtuous cycle.3

Table 1.

Benefits of Clinical Research in a Clinical Hepatology Practice

Competitive for site selection relative to university setting because of potential for high subject enrollment and short start‐up time

Bring recognition and referrals to your practice

Serve the community and offers treatments not otherwise available to patients

Additional source of revenue

Intellectually rewarding

Before you embark on the process of developing a clinical research program, you need to determine whether you have the right target population and sufficient resources, including time, equipment, space, and supportive colleagues and staff. A substantial amount of effort and cost are involved in the start‐up process. Each institution has a feasibility process that includes IRB charges, identification of potential subjects, time and travel to investigator meetings, and collection of regulatory documents. There are fixed costs to doing a study, including institutional overhead, coordinator salary, and laboratory and facility fees. Make sure that your budget reflects the appropriate amount of work relative value units required for both an initial screening visit (corresponding to approximately an initial level 3‐4 visit) and for follow‐up visits (usually an established patient level 2‐3 visit) that would correlate with the amount of detail required in the physical examination and review of adverse events. It is critical to have an experienced research manager who understands the costs of doing research at your institution.

In addition to experienced staff, to be successful, it is essential to have the support of your colleagues, to help identify potential research subjects and participate as subinvestigators. You will need to determine how to incentivize them to attend investigator meetings when you are unavailable, and help with study visits and adverse event reporting when you are out of town or on call. You also need the support of your clinic staff, who need to understand that checking in and rooming research patients is as important as it is for routine clinic patients.

The process of starting up a study site usually begins by completing a confidentiality disclosure agreement. You then review the trial synopsis and determine whether the study is a good fit for your site. Sponsors require completion of a feasibility survey, which provides details of your research site and patient population to confirm your site's ability to conduct the study. The importance of a patient database cannot by overemphasized. Knowing the characteristics of your patient population will allow you to complete the feasibility survey quickly and accurately. Screening and enrollment targets need to be realistic; sponsors will quickly recognize if they are inaccurate or discordant from other experienced investigators.

Once you confirm your interest in the study, the sponsor or contract research organization (CRO) conducts a site qualification visit to verify the research infrastructure and meet the study team and pharmacy staff. This visit provides an important opportunity to engage the sponsor and demonstrate you have the system in place to see research subjects, process laboratory samples, and maintain a rigorous chain of custody and temperature‐controlled storage for investigational products.

If your site is selected by the sponsor, the next steps are to develop an IRB application tailored to your institution and begin the process of negotiating the contract or grant. This requires familiarity with financial and legal language. Ask yourself three important questions (Table 2) and if the answer to any of these questions is no, decline the trial.

Table 2.

Important Questions to Ask When Developing a Clinical Trial Budget

1. Are the scientific value and ethical quality of the study acceptable?

2. Do I have an adequate pool of potential subjects?

3. Does the proposed budget support the work described in the protocol?

The next step is developing the clinical trial budget by identifying your costs. Costs can be broken down into categories: start‐up, study level, per‐subject, administrative, and other costs (Table 3). Consider the sponsor's initial budget offer to be a starting point. If you are dealing with a CRO, remember that it is contracted by the sponsor to keep costs at a minimum; therefore, you should call the sponsor to discuss if costs seem unreasonably low. At the same time, avoid padding the budget as sponsors will readily see through this tactic.

Table 3.

Costs to Consider When Developing a Clinical Trial Budget

Start‐up Costs

Protocol review by investigator/study coordinator

Determining potential number of eligible subjects

Site selection visit

Site initiation visit

Off‐site meetings (investigator's meeting)

Detailed budget development

Regulatory document preparation

IRB fees for submission, copies, and amendments

Advertising and patient recruitment

Pharmacy protocol review/setup costs

Study Level Costs

Screening logs

Screen failures

Electronic data management training

Recruitment

IRB fees

Fees for pharmacy setup

Storage

Other study visits

Additional regulatory submissions (amendments, serious adverse events)

Monitoring visits

Study initiation (all‐inclusive)

Per‐Subject Costs

Initial enrollment costs

Subject screening (medical history, physical examination, informed consent, laboratory work, X‐rays, etc.)

Screen failures (How many will study allow?)

Physical examinations and medical assessments

Office visits

Laboratory work, radiology, cardiology, and other medical procedures (professional fees)

Pharmacy dispensing and drug administration

Room charges and hospital bed

Medical supplies

Film duplication

Study drug storage facilities (locked cabinet/refrigerator)

Telephone contact

Patient instructions

Administrative Costs

Data collection, management, and analysis

Site visit preparation, study monitoring, and study queries

Office supplies

Shipping/dry ice

Off‐site storage

Telephone charges

Other Costs

Investigator fee

Study coordinator fee

Subject stipend

Institutions may be willing to subsidize a study with a modest budget if it is an early‐phase study, one that is likely to have a high impact, will lead to an important publication, or will bring favorable recognition to your institution in the media or other outlets. Consider approaching your institution for assistance in these circumstances.

Once you have developed your budget, compare it with the sponsor's budget. Are the per‐subject costs equivalent? Is overhead accurately represented? Are costs at the study level comparable? Negotiate with the study sponsor, but be sure to provide flexibility for renegotiation. Ultimately, studies should be revenue‐neutral regardless of enrollment. Establish payment terms and determine what payments can be invoiced and when.

Before subject recruitment can begin, there is usually a site initiation visit. Study personnel then attend an investigator meeting, which may be in‐person or web‐based. Research supplies and investigational drugs are sent to your site. Once IRB approval and a clinical trial agreement are finalized, you are ready to recruit subjects. Once again, a patient database is helpful by including patients who have expressed interest in participating in clinical trials.

In summary, incorporating a research program into a clinical practice is feasible and can be intellectually and financially rewarding. A successful research program can diversify your practice, serve patients in your community, and bring more enjoyment to your daily work.