Supplement-Applying Evidence-Based Medicine to Dietary Supplements

By Patrick J. Bryant, PharmD

Decisions made strictly on personal experience, instead of evidence from well-controlled, randomized trials with adequate sample size, often overestimate the efficacy and underestimate the safety risks associated with drugs.1 In order to more accurately estimate safety and efficacy, evidence-based medicine (EBM) is experiencing increased use in conventional medicine practice. It is our intent to bring to you this same rigorous critical evaluation of the dietary supplement literature through this publication.

By applying only information supported with sound evidence in the literature, we ensure that the knowledge we act on and pass onto our patients/customers, in addition to other health care practitioners, is valid and accurate. EBM concepts are especially important in the study of dietary supplement information since, unlike prescription medications, dietary supplements are not required to undergo review and approval by the FDA. The studies conducted on the safety and efficacy of dietary supplements are never critically evaluated by FDA reviewers and scientific experts on the FDA Advisory Panel. With an EBM review of the available information on a specific dietary supplement, you can at least be assured that some critical evaluation regarding efficacy and safety has occurred.

The EBM Process

Various processes exist to conduct an EBM review. We will use a process originally described by Cook and Guyett2 that we have modified to simplify application to clinical practice. This process involves the following steps.

Step 1: Identify, retrieve and, if necessary, translate into English the body of scientific literature associated with a particular dietary supplement.

Step 2: Perform a standardized, disciplined, and rigorous critical evaluation of those clinical studies that have the best design and largest sample sizes. This evaluation is performed in an identical manner for each EBM review using a standardized checklist of characteristics required for a scientifically sound study.

Step 3: Identify the major limitations of each trial from the critical evaluation. The key considerations may be major strengths or limitations, and include: dosage, length of study, power, sample size, inclusion criteria, blinding, randomization, evaluation measurements, ap-propriate statistical tests, and conclusions.

Step 4: Assign a Level of Evidence rating to each trial based on the critical evaluation and identified limitations. (See Figure 1.) The term "clinical impact," as used in the rating, takes into account not only the statistical power of the trial, but the sample size and the amount of patient exposure for the disease state. For example, a trial of a treatment for common cold symptoms that includes 100 patients may meet statistical power and be considered to have a fair sample size, yet has low clinical impact because 100 patients is a small percentage of the millions of patients who suffer common cold symptoms each year. Conversely, a trial in 50 patients with a disease that occurs in only 5,000 patients per year might be a high clinical impact study. There are no hard-and-fast rules about the numbers for determination of clinical impact; much depends on professional judgment.

Step 5: In situations where very little published scientific literature exists on a dietary supplement, a Benefit-Risk Assessment will be conducted. This assessment process is identical to that used when this issue exists with prescription drugs. The available data first will be reviewed to assess safety. Any known or possible benefits to the patient will then be weighed against the known or possible risks determined from the safety evaluation.

Product safety information to be considered in this situation will include purity, formulation standardization, known pharmacological effects, and known or theorized adverse events. Patient considerations also factor into this assessment, such as the severity, duration, or self-limiting nature of the disease or condition for which the product is to be used, origin of diagnosis (by health care practitioner or self-diagnosis), concomitant disease states, and concomitant prescription or OTC medications. In addition, the likelihood of harm if treatment with the supplement does not aid the condition, masks another condition, or prevents the patient from seeing a health care practitioner will be considered.

Step 6: Develop recommendation for use of the particular dietary supplement and assign a Grade of Recommendation based on the Level of Evidence which helps the reader determine the strength of the conclusion based on the available evidence in the literature.

The Goal of EBM

The goal of this EBM evaluation is to provide an objective assessment of the efficacy and safety of a dietary supplement, taking into account the strength of the evidence used. From this assessment, a recommendation will be developed taking into consideration the use of the dietary supplement in the clinical setting.

How to Use EBM Reviews

There is a tremendous amount of information available on the more commonly used dietary supplements. The primary problem is that much of that information is anecdotal or has little to no scientific support. Utilizing that information to make clinical decisions on therapeutic plans, educate or consult health care practitioners, and counsel patients/customers is difficult, if not impossible. Use of an EBM review allows all health care practitioners to begin the decision-making process at the same level of knowledge. From there, other factors to the decision-making process depend on what is to be accomplished. It is important to add a clinical perspective to the formula as well as to understand the needs and beliefs of the consumer, especially if the goal is to incorporate this knowledge into an acceptable plan for an individual patient.

Key to all this is the understanding that, unlike prescription medications, the pharmacist and physician are not the "gatekeepers" in providing dietary supplements to the consumer; the consumer is the "gatekeeper." The physician is usually even further removed from the situation than the pharmacist. In some situations, the pharmacist is at least present at the point of sale and can influence the consumer's purchase of the dietary supplement. The pharmacist must handle this responsibility much the same way as with OTC medications and therefore must be knowledgeable about the objective scientific evidence that exists for various dietary supplements. It is our hope and goal that the EBM reviews in this newsletter will assist pharmacists and other health care providers in acquiring that necessary knowledge.

References

1. Guyatt GH, et al. Grades of recommendation for antithrombotic agents. Chest 1998; 114(5 suppl): 441S-444S.

2. Guyatt GH, et al. Rules of evidence and clinical recommendations on the use of antithrombotic agents. Chest 1992;102(4 suppl):305S-311S.