The escalating use of dietary supplements in the United States over the past few years, with herbal products representing the most rapidly growing segment, has generated new concerns related to patient safety.

These supplements are consumed by 30–40 percent of Americans, and an estimated 15 million adults are taking herbal products concurrently with prescription medication.¹ As a result, there has been a dramatic increase in published reports on adverse consequences of herb-drug interactions, including loss of drug efficacy, physiologic disturbances, skewed laboratory results, and compromised perioperative care.

These concerns for patient safety are reflected in specific questions posed by the Joint Commission on Accreditation of Healthcare Organizations to hospitals seeking accreditation. They ask how patients who bring herbal products from home are handled, whether herbs are on the hospital formulary, and whether physicians are required to assess the use of herbals during the hospital stay.²

Herb Research Foundation

Two of the more popular herbal products, St. John's wort (above) and echinacea

Impact on Research

The effect of herbal and alternative supplement use by people participating in biomedical research protocols has been a concern of NIH’s.³

Recently, NIH investigators reported a significant reduction in the bioactivity of the protease inhibitor indinavir—up to a 75 percent decrease—in HIV-infected patients who were prescribed indinavir and were also taking St. John’s wort.^{4, 5} The studies also showed that low plasma concentrations of protease inhibitors are a cause of antiretroviral resistance, treatment failure, and cross-resistance among members of this class of compounds. Such findings demonstrate that in some contexts, herbal supplements may not be the harmless agents some health-care workers take them to be.

How prevalent is the use of these natural products by patients enrolled in NIH clinical trials? In surveys conducted at the Clinical Center (CC), 25–42 percent of patients reported taking herbal and other supplements.^{6, 7, 8, 9, 10}

Encouraging Patient Disclosure

A major theme in complementary and alternative medicine literature is the communication barrier between physicians and their patients.¹¹ Though slowly changing, health professionals still do not routinely question their patients about use of herbals and other kinds of alternative supplements.

Understanding why patients seek out and use these products can help physicians and investigators detect such practices and discuss them more openly. Patients may have accepted anecdotal evidence or slick marketing as sufficient information for use and they may be unaware of the potential effect of supplements on research results, not to mention potential complications or adverse effects on their own health.

Furthermore, patients eager to be selected for a clinical trial may be hesitant, even if asked, to disclose anything that may threaten their acceptance into a protocol. They may be less reluctant once a clinical trial is under way.

Assessment of herbals and other alternative supplements may be omitted in a biomedical research setting, where significant focus is on the clinical trial. For an investigator to venture into these uncharted areas is to have to consider many issues not addressed in protocol development nor routinely raised during the institutional review board (IRB) process. However, there is a trend beginning to include questions about patient use of these natural products in protocols.

It is incumbent upon health-care providers at the CC to provide a safe environment for disclosure and to understand the strong beliefs many patients have in the value of alternative approaches. Questions must be direct, open, and specific to avoid underreporting.¹² Furthermore, to maintain a trusting credible relationship with their patients, physicians need to become educated about herbal and dietary supplements.¹³ Only through a combination of patient disclosure and availability of reliable information can there be informed decisions.

Clinical Center Policy

Understanding the complexity of the issue and recognizing the need for guidelines, the CC moved forward in early 2000 with an initiative to construct a policy to guide hospital staff in the management of patient use of herbal and alternative supplements.

An interdisciplinary task force was formed by the CC Quality Committee to assess physician, nurse practitioner, and physician assistant understanding of this issue. Further goals were to examine and benchmark practice and policy in other hospitals, draft a policy based on findings, engage focus groups throughout the CC to assist in shaping the final form of the policy, and gather input on how to achieve successful implementation.

On May 15, 2001, the CC’s Medical Executive Committee approved a policy on the "Use of patient’s own dietary supplements and alternative consumable products brought into the Clinical Center." The policy took effect June 28, 2001.

The underlying basis of the policy was that "Patients shall use their own dietary supplements and alternative consumable products only upon authorizing orders by their CC physician." This would be accomplished by the following procedures:

Through the established admission assessment process, within 8 hours of admission the nurse will screen all inpatients for current use of dietary supplements and alternative consumable products.

Products currently being used by a patient will be promptly reported to the physician in order to determine whether inpatient use is allowed. If inpatient use is allowed, the physician will generate MIS orders to authorize use of each product by name. If the physician does not specifically authorize usage, the patient will not be allowed to take the product.

Patients will be responsible for the initial and ongoing supply of these products during the course of the hospital stay.

In the focus groups held prior to policy approval, medical staff strongly voiced their need for resources to support decision-making in clinical practice—the tools to learn about these products and easy access to existing scientific evidence on risk. In response, the CC secured a site license for an online database of herbal monographs. The selection of the Natural Medicines Comprehensive Database was based on its scientific integrity, completeness, ease of navigation, timely updating of existing data, and ongoing addition of new products as they become popular.¹⁴ The database became available on desktops throughout the CC on August 1, 2001.

Policy Implementation

The standards of practice for nurses were changed to incorporate use of herbal and alternative supplements as a mandatory area of inquiry during the admission assessment process, and computerized nursing documentation screens were modified accordingly. A new set of physician order screens was also constructed to document approval of continued use by a patient of his or her own supply of such a supplement during hospitalization.

It was also decided that the same process would be applied in the outpatient setting: Outpatient nurses would use the same standard of practice and documentation pathway, ascertaining whether patients on protocol were using herbal or other supplemental products and then alerting the physician to the findings. The physician would then determine whether the patient should continue use—and, ideally, engage in open dialogue with the patient about the issues that informed that decision.

Around the Corner

The implementation of the Herbal and Alternative Supplement Policy will inevitably lead to other necessary steps within the CC to help raise awareness and to ensure compliance. IRBs might contemplate including a section on patient use of herbal and alternative supplement products in all protocols; expectations that patients will disclose and discuss such use with their physician might be included in the written informed consent.

The challenge to clinical investigators and biomedical research facilities is to create policies and follow practices that respect the choices of individuals participating in clinical trials while ensuring patient safety and preserving the scientific integrity of the study.

References

1. D. Eisenberg, R.B. Davis, S.L. Ettner, S Appel, S. Wilkey, M. Rompay, and R.I. Kerssler. "Trends in alternative medicine use in the United States, 1990–1997: Results of a follow-up national survey." JAMA 280: 1569–1575 (1998).

2. Joint Commission on Accreditation of Healthcare Organizations, 2000 Hospital Accreditation Standards. TX.3.3, 113 (JCAHO, Oakbrook Terrace, IL, 2000).

3. A. Sparber, W. Jonas, J. White, E. Derenzo, E. Johnson, and S. Bergerson. "Cancer clinical trials and subject utilization of dietary supplements: A case study." Cancer Invest. 5:436–439 (2000).

4. C.A. Roby, G.D. Anderson, E. Kantor, D.A. Dryer, and A.H. Burstein. "St John’s wort: effect on CYP3A4 activity." Clin. Pharmacol. Ther. 67:451–457 (2000).

5. S. Piscitelli, A. Burstein, D. Chaitt, R. Alfaro, and J. Falloon. "Indinavir concentrations and St John’s wort." Lancet, 355: 547–548 (2000).

6. A. Sparber, L. Bauer, G. Curt, D. Eisenberg, T. Levin, S. Parks, S. Steinberg, and J. Wootton. "Use of complementary medicine by adult patients participating in cancer clinical trials." J. Altern. Complement. Med. 27: 623–630 (2000).

7. A. Sparber, J. Wootton, L. Bauer, G. Curt, D. Eisenberg, T. Levin, and S. Steinberg. "Use of complementary medicine by adult patients participating in HIV/AIDS clinical trials." Oncol. Nurs.Forum 6: 415–422 (2000).

8. E. Johnson, J. Wootton, R. Kimzey, L. McCullagh, D. Byrd, K. Singh, D. Rubino, and F. Pucino. "Use of herbal therapies in an ambulatory care research setting: An exploratory study." J. Altern. Complement. Med. 6: 429–435. (2000).

9. D.S. Shrader, B. Bacon, K. Lindsay, D. La Brecque, T. Morgan, E. Wright, A. Farooq, J. Hoofnagle, and L. Seefi. "Use of complementary and alternative medicines among patients with liver disease." Paper presented at the CAM and Chronic Liver Disease Conference sponsored by the NIDDK/NCCAM in Bethesda, Maryland (August 1999).

10. A. Kim, R. Davey, and S. Piscitelli. "Use of complementary medicine and dietary supplements in HIV-infected patients." Poster presented at annual NIH summer student poster day (July 2001).

11. J. Wootton and A. Sparber A. "Surveys of complementary and alternative medicine: Part I. general trends and demographic groups." J. of Altern. Complement. Med. 7: 195–208 (2000).

12. D.D. Silverstein and A.D. Spiegal. "Are physicians aware of the risks of alternative medicine?" J. Community Health 26: 159–174 (2001).

13. D. Hensrud, D. Engle, and S. Scheitel. "Underreporting the use of dietary supplements and nonprescription medications among patients undergoing a periodic health examination." Mayo Clin. Proc. 74: 443–447 (1999).

14. Book review: The Natural Medicines Comprehensive Database. JAMA 283: 2992 (2000).

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