Companion Diagnostics: Challenges in the development of pharmacist-based point-of-care tests

Patients are expecting to receive these home-approved tests and screens in the community pharmacy. Home-use tests and Clinical Laboratory Improvement Amendment (CLIA)-waived tests are not synonymous², but both have been considered point-of-care tests (POC) by various authors³. For the purposes of this article, POC is defined as: performing a test outside of a traditional laboratory that produces a reliable result rapidly to aid in disease screening, diagnosis and/or patient monitoring⁴. Unlike tests approved for ‘home use’, CLIAwaived tests are intended to be used by individuals trained in properly conducting and interpreting the tests despite their classification as ‘simple to use’.

In an industry of discovery and development, federal regulation from a variety of United States’ (US) departments and agencies is expected. Innovators in health care products and companion diagnostic tests expect a degree of regulatory oversight, but rarely expect that every state and jurisdiction may manage that oversight differently. Product regulation is most often a task assigned to the federal government, because these products enter into interstate commerce. The regulation of people, in this case health care providers, is reserved to the states and jurisdictions under the 10th Amendment to the US Constitution. Navigating the pharmacist regulations for all 50 states and additional jurisdictions can seem nearly impossible. This article will review the commonalities of professional regulation amongst all states and jurisdictions, as well as offer areas of difference to be considered by drug and point-of-care testing developers and manufacturers. Projected changes in regulation and opportunities for industry collaboration will be highlighted.

Each state and jurisdiction (Washington DC and US Territories) will have a definition of the practice of pharmacy called a ‘scope of practice’ and codified by state law. Each scope of practice will list those professional tasks and functions requiring licensure as a pharmacist. Most states have a process whereby any professional act not expressly listed in the law will require a ruling by a governing body – a Board of Pharmacy, a Board of Public Health, a Department of Professional Licensing, etc. In a few states, the law is absolute and any task not specifically listed in law is disallowed.

Pharmacists’ responsibilities vary

All pharmacists, regardless of state and jurisdiction, have the professional ability to dispense drugs, to counsel patients, and to provide comprehensive care with regard to pharmacotherapy. Likewise, pharmacists in each state are allowed to administer vaccines, but limitations on this service vary greatly. By way of example, in Nebraska, pharmacists are allowed to administer all vaccines to patients of any age; in New York pharmacists are prohibited from vaccinating children. There are similar variances among the state regulations that allow for pharmacists to conduct POC in community pharmacies. Many states’ laws and regulations are moot regarding pharmacist-based POC; others are progressive on the issue, writing into the pharmacists’ scope of practice legislation the authority to order and conduct lab tests and to make pharmacotherapy decisions based on the results.⁵ Kansas not only recognises this process as a pharmacist’s professional function, but has declared it to be unprofessional conduct to order or run unnecessary tests⁶.

A final element to the functionality of companion diagnostics in community pharmacies, where the pharmacist or technician will conduct the test and the pharmacist will professionally act upon the result, is the necessity for the result to be actionable. It is the professional action taken by the pharmacist that is regulated differently in nearly every state and jurisdiction. This action, the seamless use of the test results, is accomplished in a variety of ways depending upon the state or jurisdiction. In some states, the pharmacist will work under protocol or collaborative agreement with a single diagnostician or prescriber. In others, there will need to be collaboration with multiple diagnosticians or prescribers. Advanced practice pharmacists in yet other states will be able to make these decisions independently⁷.

If a true ‘companion’ diagnostic is developed, pharmacists will receive a single prescription that includes both the diagnostic test and the drug. This combination will by-pass the collaboration requirements in many states. There will likely be pharmacotherapeutic agents where a test will be required prior to dispensing a refill. Examples in practice today include a pregnancy test for an isotretinoin product or a white blood cell analysis for clozapine-containing drugs. Currently, patients cannot undergo these tests in a community pharmacy. Adherence to prescribed therapy could be improved if CLIA-waived tests, appropriate for this monitoring, were available. Pharmacists are currently testing for and treating influenza and Group A Streptococcus^{8, 9, 10}. For many years, they have tested international normalised ratio and adjusted anticoagulant doses, tested haemoglobin A1c and adjusted hypoglycaemics and insulin doses^11,12,13. The pharmacies offering these services have an existing CLIA certificate of waiver. Over 1,350 pharmacist and pharmacist interns have completed a certificate-training program in Community Pharmacy Based Point of Care Testing¹⁴, indicating that community pharmacy is well positioned to participate in this process for an expanding number of companion diagnostics.

In addition to the scope of practice laws and differences in authority, via collaboration or independent authority, there will be a state agency or department charged with the regulation of the CLIA and certificates of waiver. Research by Sallach shows that these agencies and departments are also varied¹⁵. In the vast majority of states reporting, the community pharmacy needs only to follow the federal law governing CLIA and certificates of waiver. Four (8%) of the reporting states and jurisdictions (51/57) note having state laws in addition to federal requirements: California reported more stringent state requirements, Maine reported expanded requirements, Nevada reported having additional personnel restrictions, New York expressly limits those people who may perform CLIA-waived tests and currently excludes pharmacists. Most US Territory’s laboratory regulations are managed by state agencies: American Samoa uses the Hawaii State Agency; Guam and Saipan use the regional office in San Francisco, California; and the Virgin Islands use the New York regional office. Interestingly, the Boards of Pharmacy do not always agree with the information provided by the state or jurisdiction laboratory division. With this confusion, it is often difficult for the innovators and developers of POC to know when to approach community pharmacists as collaborators.

The decision to develop tests and companion diagnostics appropriate for use in a community pharmacy will be based on several variables¹⁶:

1. Is the patient likely to be receiving the prescription or over-the-counter drug being monitored at a community pharmacy? If the drug is used only during surgery, for instance, the community pharmacist will not be a reasonable resource. If, however, the drug being monitored treats a chronic condition, the patient is likely getting those prescriptions filled in the community pharmacy.
2. What is the analyte for the test and what is the volume? Many states and jurisdictions require separate licensure or credentialing as a phlebotomist, therefore large volume blood draws, even for a CLIA-waived tests, will not be possible in the pharmacy. There are some samples that cannot be easily collected in the community pharmacy – faecal testing would be difficult, for instance. There are CLIA-waived tests that can be performed on patient self-collected samples, but the collection has to be easy and straightforward.
3. The test has to meet the standard of rapid; meaning results in less than 60 minutes. Results in 10 minutes would be optimal.
4. The test and any machinery needed to read the test must have a small footprint and not require specialised storage conditions. In community pharmacies, professional space is limited. The optimal ‘reader’ would read multiple tests and be safe to leave in the patient counseling space unattended while running. This means the patient cannot interfere with the test and cannot be exposed to the analyte nor the reagent used.
5. If there is no mechanical assistance with reading a test, the results must be visible and accurate for a length of time to allow the pharmacist or technician to walk away from the test without a need to return at exactly the right moment for an accurate reading.

There will be instances where a CLIA-waived test is not available. Considering the community pharmacist may still be an option. Today, pharmacies are screening for Hepatitis C and HIV infections^{17, 18}. These are not diagnostic tests, but the pharmacists are serving to get the patients with reactive tests into the health care system. Community pharmacies are also reasonable sample collection sites. Rebecca Chater, RPh, MPH, FAPhA, an executive healthcare strategist at Ateb Inc, notes that pharmacogenomic testing services offer an opportunity for community pharmacies to improve patient care and avoid drug problems when genomic variances could compromise a drug’s efficacy and/or safety¹⁹.

Transitioning times

The laws and regulations around pharmacist-led POC are changing rapidly. This is due to: patients demanding accessible and convenient care; an expanding shortage of primary care providers^{20, 21}; and the training necessary for pharmacists to order, conduct and evaluate tests becoming a mandatory skill in colleges and schools of Pharmacy in the US²². Many of today’s frustrations with variations in regulation will start to resolve as the regulators embrace this professional service provided by pharmacists. This transition is very similar to the changes in regulation seen when pharmacists became vaccinators, however the recognition of POC is moving even more quickly²³.

The creating of companion diagnostics suitable for CLIA-waived POC will hasten this transition and will improve patient convenience and ultimately patient adherence to pharmacotherapy. Moving required monitoring tests and pre-dose tests to the pharmacy will enable the patient to receive needed pharmacotherapy in a much more timely fashion. The American Pharmacists Association, the national US association representing all pharmacists, will consider new policy on POC during their annual meeting in March 2016²⁴. This, too, will increase the recognition that pharmacists can serve a pivotal role in patient care using companion diagnostics. Laws and regulations will mirror this recognition.

It is essential that the pharmaceutical industry considers POC early in the drug development and safety monitoring processes. When companion diagnostics and new drugs are presented to federal regulators as a ‘package deal’, the recognition will expand from state regulation of professionals to the federal government regulation of product, where this industry has much more experience and comfort. States and Territories will still have the ultimate authority to regulate their professionals, but they are unlikely to craft or maintain laws and regulations that will decrease patient access to care or patient convenience. Working with community pharmacists on the front line of drug dispensing and the recognised pharmacotherapy experts on the health care team makes sense for all involved.

References

1. Overview of Companion Diagnostics in the Pharmaceutical Industry; Stephen Naylor and Toby Cole; Drug Discovery World; Spring 2010
2. Title 42 CFR Chapter IV Subchapter G Part 493; Public Health, Laboratory Requirements
3. CLIA Waived Tests; CDC; https://wwwn.cdc.gov/clia/Resources/WaivedTests/; accessed 20 October 2015
4. Gubbins PO, et al. Point-of-care testing for infectious diseases: Opportunities, barriers, and considerations in community pharmacy J Am Pharm Assn. 2014;54:163-71
5. 2012 Minnesota Statutes 1501.01 Subdivision 27
6. 2006 Kansas Code – 65 – 1626 (hh)(10)
7. 2015 California Statue: Section 4016.5
8. Klepser D, et al. Time and motion study of influenza diagnostic testing in a community pharmacy. Innovations in Pharmacy. 2014;5:1-8
9. Klepser DG, et al. Health Care Resource Utilization and Cost for Influenza-like Illness Among Midwestern Health Plan Members. J Manag Care Spec Pharm. 2015;21(7):568-73
10. Collins S. Point-of-Care testing: Emergency market, opportunity for pharmacists; Pharmacy Today; APhA; https://www.pharmacist.com/point-care-testing-emerging-market-opportunity-pharmacists; accessed October 2015
11. Witt DM, et al. Effect of a Centralized Clinical Pharmacy Anticoagulation Service on the Outcomes of Anticoagulation Therapy; 2005;127(5):1515-1522 doi:10.1378/chest.127.5.1515
12. Developing Trends in Delivery and Reimbursement of Pharmacist Services; Avalere Health LLC; November 2015; pp 3
13. Bunting BA. Training Pharmacists for Disease Management Roles; Pharmacy Times; 1 October, 2007 (online)
14. Sara Roszak, Director of Research programs, National Association of Chain Drug Stores Foundation; personal correspondence; October 2015
15. Rory Sallach Ruma, PhD, PharmD. Point-of-Care in Community Pharmacies; podium presentation; Asheville, NC; January 2015
16. Kenneth Hohmeier. University of Tennessee; Preliminary research data; November 2015
17. Darin KM, et al. Pharmacist-provided rapid HIV testing in two community pharmacies. J Am Pharm Assn. 2014:e7-e14. doi:10.1331/JAPhA.2015.14070
18. Heath D, et al. Screening for human immunodeficiency virus and hepatitis C virus in communities: an emerging opportunity. Michigan Pharmacist. 2012;50:40-3
19. Hesselgrave B. Pharmacogenomics: Right med, right dose, every time; Drug Topics; October 2015; vol 159; No 10: pp22
20. Projecting the Supply and Demand for Primary Care Practitioners Through 2020; http://bhpr.hrsa.gov/healthworkforce/supplydemand/usworkforce/primarycare/; accessed September 2015
21. Prognosis E-New; Wayne State University School of Medicine; Michigan Academy of Family Physicians elects residency director Pierre Morris, MD, to leadership role; 20 August 2014
22. Accreditation Council for Pharmacy Education Accreditation Standards and Guidelines for 2016
23. Higginbotham S, Stewart A, Pfalzgraf A. Impact of a pharmacist immunizer on adult immunization rates; J Am Pharm Assoc (2003) 2012;52:367-371. doi:10.1331/JAPhA.2012.10083
24. Theresa Tolle, BSPharm, FAPhA; Speaker of the APhA House of Delegates 2015-2016; personal correspondence; July 2015

Biographies

Dr. Ally Dering-Anderson, Clinical Assistant Professor at the Department of Pharmacy Practice, University of Nebraska College of Pharmacy, is a community pharmacist. Ally was the 2015 College of Pharmacy Teacher of the Year. She has spoken nationally and internationally on community pharmacy topics. Her interests include point-of-care testing, excellence in education, medical marijuana and public health policy. Her correspondence details are: Dr. Ally Dering-Anderson; University of Nebraska College of Pharmacy; 986045 Medical Center; Omaha, NE 68198-6045

Meagan Doyle is a senior-level pharmacy student at the University of Nebraska College of Pharmacy. She is the past-president of the Student Alliance for Global Health at UNMC and a coordinator for the Bridge to Care mentoring program which she presented at the Global Health Conference Midwest 2015. Her career interests include cardiology.