Opinion: Approaches to Set Up Principal Investigators for Success

Molly Downhour, Clinical Research Strategy Executive, Medix

Clinical Researcher—June 2018 (Volume 32, Issue 6)

PEER REVIEWED

Molly Downhour, MHA, BSN, NEA-BC, OCN, CCRC

[DOI: 10.14524/CR-18-0002]

 

Show of hands—how many people believe that principal investigators (PIs) are not currently set up for success? Odds are that not many hands would go up with confidence after that question.

As the perception of this role in the drug and device development industry currently stands, it is not surprising that the number of active PIs continues to decline.{1} This can gut enthusiasm for opportunities in the field, which is a shame, because being a clinical research investigator used to be a coveted role. What happened, and how can we turn the tide to encourage young clinicians to seek out opportunities to lead clinical research?

What is the Problem?

The problem is the lack of PI oversight and engagement in clinical research. Over the last decade, the number one cause of Form FDA 483s (Inspection Observations) leading to Warning Letters from the U.S. Food and Drug Administration to PIs was protocol compliance issues, such that “an investigation was not conducted in accordance with the signed statement of the investigator.”{2}

By signing Form FDA 1572, PIs agree to take on full oversight of the clinical trial, including the investigator agreement, adherence to the protocol and investigational plan, and ensuring the rights, safety, and welfare of all clinical trial participants. This is a daunting task, considering most PIs are not directly responsible for the hiring, training, and allocation of available resources for the research team members within their oversight who are delegated to complete various clinical research tasks.

The conundrum is the incongruence between the government regulations requiring full responsibility of oversight to be owned by the PI, versus the operational practice most often owned by a healthcare administrator. To be honest, I prefer the PI to be the scientific and medical expert on the clinical trial and leave administrative functions to the professionals with expertise in that area.

Let’s not forget that the list of additional stressors on the economic healthcare landscape contributing to the decline in investigator oversight and engagement includes:

  • Decreased National Institutes of Health grant funding available to support academic careers.{3}
  • Increased regulatory requirements regarding adherence to International Council for Harmonization guidelines, the U.S. Health Insurance Portability and Accountability Act mandates, and U.S. government Meaningful Use standards for using electronic health records.{4}
  • Study budgets have remained static, despite trends of greater study complexity and requirements, including exponential increases in terms of electronic data capture systems each requiring lengthy training and unique logins.{4}
  • Lack of adequate supporting research staff.{5}
  • Lack of dedicated time for research activities.{6}
  • Lack of financial incentives and/or recognitions.{6}
  • Lack of PI orientation or training for the responsibilities for clinical research, despite those in this role having the most responsibility for complete oversight of the clinical trial activities per the 1572.{6}

In summary, as an investigator, you’re faced with less funding, less time available, fewer resources, lack of training on clinical trials operations, and 100% responsibility of oversight on a team you with many members whom you neither hired nor trained. Sign me up!

However, there are obviously sites full of professionals that conduct clinical trials very well, indeed. These sites have institutional support to ensure the above issues are addressed in their organizational infrastructure.

With severe limitations in the availability of grant funds, site administrators have the difficult job of balancing their clinical trial portfolios amongst industry-sponsored, grant-funded, investigator-initiated, and cooperative group trials, all while meeting the community needs for innovative treatment options. These site administrators dig deep to find their true costs of running trials, and justify the amounts in their study budgets.

Truly thoughtful administrators will turn down trials with inverse expense to revenue ratio if the trial provides no other value to their sites. These site leaders understand the need to operate like a business; not accepting revenue losses simply because it is research. The culture and expectation at these sites is that adequate investigator time and resources are given for research and, in return, the sites meet research and accreditation standards. Standout sites include Duke Clinical Research Institute, clinical trials units at such other academic medical centers as the ones based out of Northwestern University and Baylor University, the Sarah Cannon Research Institute, and the HonorHealth system in Arizona.

How to Make the PI Role Attractive Again

Sharing Success Stories

The first thing I would do is highlight successful investigators in a variety of therapeutic areas and share their success stories. What are the common denominators that they share? My educated guess is that these PIs have been influenced by great mentors, have dedicated time for clinical research activities, and are part of a site that invests in the infrastructure required to execute clinical trials well, instead of demanding to financially break even on day one.

All of the above-mentioned qualities allow exceptional PIs to focus on their research and practice responsibilities, instead of on the types of administrative duties that can be handled by non-physicians on site. Further, both new and ongoing PIs who want to reach and remain on the leading edge of trials will seek out other successful investigators and network with them at industry events or other opportune moments.

An example of a defined and successful mentoring program is HonorHealth’s Drug Development Scholar program. This program recruits young oncologists and hematologists with a passion for drug development. The one- to two-year program focuses on early-phase clinical trial development, patient recruitment and follow up, statistical analysis, bioinformatics and regulatory affairs.

The scholar functions as a specialist physician, performing duties involving direct care of patients with advanced malignancies and those receiving treatment on clinical trials, evaluating new patients, and formulating treatment plan under supervision of the assigned faculty member.{7} The Drug Development Scholars are fully immersed in the program, with interaction with all of the research staff.

The American Association for Cancer Research and the American Society of Clinical Oncology also support an annual educational workshop on “Methods in Clinical Cancer Research.” The  July 2018 event is described as an “intensive workshop in the essentials of effective clinical trial designs of therapeutic interventions in the treatment of cancer for clinical fellow and junior faculty clinical researchers in all oncology subspecialties, including radiation and surgical oncology and radiology.”{8}

Encouraging Nurse Practitioner Participation

My second recommendation is to encourage experienced nurse practitioners (NPs) to participate in clinical research as principal and sub-investigators. NPs are currently underutilized in clinical research, despite many of them having followed research curricula in advanced degree programs.

There is no regulation that requires PIs to be physicians. Per the Code of Federal Regulations in CFR 312.53 and 812.43, sponsors of clinical investigations are required to select investigators who are qualified by education and experience as appropriate experts to investigate the test article, whether investigational product or device.{9} Not only does the inclusion of NPs as PIs and sub-investigators increase the pool of investigators to execute trials (thus helping more patients and advancing science), it also may raise the bar on the quality of the execution of clinical trials due to their holistic training.{10}

Major pharmaceutical companies such as Celgene, Eli Lilly, Aveo, Nektar, and AbbVie have all sponsored studies run by NP PIs. Central institutional review boards such as Western IRB have and will approve qualified NPs to be PIs on industry-sponsored trials. While physician PIs are far more common than NP PIs, there is an established precedent to build upon.

Emphasizing Training

Regardless the educational background and professional licensure of investigators, they all need adequate training on the responsibilities of being a clinical investigator. Do they understand the requirements on Form FDA 1572 and the consequences of not fulfilling the relevant duties?

Clinical investigator training programs are offered by the Association of Clinical Research Professionals, the National Institutes of Health, the Collaborative Institutional Training Initiative, and academic and private organizations. Site leaders can take the training further and pay for their investigators to become certified as PIs; this demonstrates to sponsors their dedication to the role.

Sites also need a thorough investigator orientation process and competency checklist. The site orientation helps investigators understand how the site operations support their responsibilities in clinical trials oversight. An orientation should lead to routine meetings with the research staff to review and discuss research participants and documentation, and to provide guidance on reporting adverse events, updates on performance status, clinical significance of assessments, and standard operating procedures on training for new protocols and amendments.

Conversely, when taking a role at an institution, physicians and NPs should be turning the tables to ask what resources are available to be successful in the investigator role. Does the site have adequate staffing (including a low turnover rate on staff), a positive reputation in the industry, and administrators who understand the unique needs of running clinical trials? Are financial payments designed to incentivize or de-incentivize participation in clinical trials? Investigators are obviously going to have better engagement and oversight when they choose to work at sites where the leadership understands the requirements and value of conducting clinical research.

Conclusion

Without a team effort, we will continue to see the number of investigators decline. Sites need to seek sustainability, conduct high-quality training and mentoring for new PIs, and explore expanding the talent pool with experienced NPs. Site leaders need to ensure sites are set up for success for all employees—including investigators.

References

  1. Corneli A, Pierre C, Hinkley T, Lin L, Fordyce C, Hamre G, Roe M. 2017. One and done: reasons principal investigators conduct only one FDA-regulated drug trial. Contemp Clin Trials Comms 31–8. https://www.sciencedirect.com/science/article/pii/S245186541630093X
  2. U.S. Food and Drug Administration. 2018. Inspection Observations. https://www.fda.gov/ICECI/Inspections/ucm250720.htm
  3. Lauer M. 2016. National Institutes of Health/Office of Extramural Research. https://nexus.od.nih.gov/all/2016/05/31/how-many-researchers/#
  4. Morgan C. 2017. Is clinical trial design complexity behind the high tunover rate for principal investigators? MedCity News. http://medcitynews.com/2017/04/high-turnover-rate-for-principal-investigators/
  5. Jacobs SR, Weiner BJ, Reeve BB, Weinberger MM, Good MJ. 2014. Organizational and physician factors associated with patient enrollment in cancer clinical trials. Clin Trials, 565–75.
  6. Rahman S, Azim MA, Shaban SF, Rahman N, Ahmed M, Bin Abdulrahman K, D’Souza UJ. 2011. Physician participation in clinical research and trials: issues and approaches. Advances Med Ed Pract, 85–93.
  7. HonorHealth. 2018. https://www.linkedin.com/jobs/view/physician-drug-development-scholar-at-honorhealth-544505968/
  8. AACR/ASCO. 2018. Methods in Clinical Cancer Research. http://vailworkshop.org/Pages/AboutWorkshop.aspx
  9. U. S. Food and Drug Administration. 2018. Title 21 Food and Drugs. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.53
  10. Hersher R. 2012. Nurses on trial. Nature Med, 1165–7.

Molly Downhour, MHA, BSN, NEA-BC, OCN, CCRC, (mdownhour@medixteam.com) is a Clinical Research Strategy Executive at Medix.