Creating drug monographs and drug class reviews in an evidence-based formulary system

April 25, 2008

P&T committees can create evidence-based formularies with a variety of tools and proven methods of evaluation

Creating drug monographs and drug class reviews in an evidence-based formulary system

Sheri A. Strite; Michael E. Stuart, MD; Shaun Urban, RPh

An evidence-based drug formulary is an important tool that provides high-quality information to aid decision making and to ensure the formulary inclusion of drugs demonstrated via validated research to have clinical usefulness. 1 Drug monographs and drug class reviews are the foundation of high-quality formulary systems. When monographs and class reviews are created using a rigorous evidence-based process, they can be used for formulary decision making, to guide clinical care decisions, and compare drug alternatives. This paper discusses the importance of an evidence-based formulary process and outlines the steps required for creating high-quality, evidence-based drug monographs and drug class reviews.

Clinical judgments should be made, by validated evidence whenever possible. Yet, the development of a high quality evidence-based formulary is jeopardized by lack of clinician training in critical appraisal of the evidence, and is compounded by the weekly publication of thousands of flawed and misleading studies and opinions, even in the best medical journals. Each week, approximately 12,000 articles are added to the National Library of Medicine. It is our estimate, having evaluated thousands of published studies, that =10% of published studies in the healthcare literature are both valid and clinically useful; others have estimated that this number is less than 5%. 2 In discussions concerning the state of scientific knowledge, the Institute of Medicine concluded that it was plausible that only 4% of interventions used in healthcare have strong evidence to support them. 3

Critical appraisal matters. Chalmers et al 4 demonstrated that a lack of concealment of allocation inflated the appearance of benefit, as did a lack of randomization. Studies that were randomized with concealment of the allocation sequence reported nonsignificant findings. As studies diminished in quality in these 2 dimensions, benefit was inflated as high as 10% in favor of the intervention. This translates into a number-needed-to-treat of 10, which would be highly clinically significant. Results of subsequently published studies have supported the conclusion that bias tends to favor the intervention, inflating benefits by up to a relative 40% to 50%. 5-9 These high rates of falsely inflated results have been demonstrated in studies in which methods, such as generation of the randomization sequence, concealment of allocation, blinding, and assessing outcomes through statistical modeling, are omitted or not done correctly. 5-9 Skilled formulary groups can help fill this quality information deficit by conducting rigorous critical appraisals of the medical literature for validity and usefulness of drugs being considered for formulary inclusion. An evidence-based approach is the only reliable way to know if the drug being evaluated is likely to be responsible for the reported outcomes in a study (i.e., the study is valid) or if the results are likely due to bias, confounding, or chance (i.e., the study is invalid). A good formulary system continuously evaluates new evidence, incorporating valid and useful information,.

BUILDING A DRUG MONOGRAPH OR DRUG CLASS REVIEW

There are 5 general steps for building a high quality drug monograph or drug class review: compile background information, identify the scientific evidence, critically appraise the evidence for validity and evaluate study results, summarize the evidence, and summarize the monograph or class review including a recommendation.

Identifying the evidence. The next step is to create a focused clinical question and then identify scientific evidence. An efficient way to find high-quality information is to obtain high quality systematic reviews, such as those listed in Table 1. The Database of Abstracts of Reviews of Effects (DARE) is particularly useful as it identifies systematic reviews, assesses them for methodological quality against a set of inclusion criteria, and summarizes the results. The National Library of Medicine, accessed through PubMed, can also be useful to find either primary or secondary references, including meta-analyses or randomized controlled trials (RCTs). It is advisable to use the drug's generic and proprietary name when searching PubMed. It is necessary to critically appraise all studies obtained from a PubMed search. Systematic reviews obtained from PubMed can be crosschecked with DARE. Editorials, comments, and related articles can provide additional information to aid in the critical appraisal process.

Although a study may be considered low quality overall, it may be sufficiently valid in one area, such as safety; therefore, it may be worthwhile to grade individual study conclusions rather than to assign a grade to the overall study.

Summarize the review and make recommendations. The final step in conducting the drug review is to create a summary. The summary should be very clear and transparent in distinguishing between evidence and conclusions or judgments. It should address the issues of efficacy and safety results, appropriate patient population, important clinical considerations, value assessment, comparison with therapeutic alternatives, implications for practice change, and recommendations. The summary should also describe limitations of the overall review and analysism

CONCLUSION

A well-written drug monograph or class review, prepared with attention to transparency, is a vital asset for a P and T committee's evidence-based decision making. Training sessions for P and T committee members describing evidence-based medicine and the important elements of critical appraisal provide efficient meetings and quality meeting decisions.

An evidence-based approach to informing formulary decisions is powerful because it provides a solid, scientific basis for making judgments about the validity and clinical usefulness of drugs. An evidence-based approach builds on appropriate study design, methodology, and execution. This evidence-based approach figures importantly into considerations of overall benefits, risks, and therapeutic alternatives,. Making these choices is a critical step for providing quality and value-based patient care.

REFERENCES

1. Strite SA, Stuart ME. Applying evidence-based pharmacotherapy to formulary decisions. In: Chiquette E, Posey LM. Evidence-based Pharmacotherapy. Washington, DC: American Pharmacists Association Publications; 2007:165-187.

2. Ebell MH. An introduction to information mastery. July 15, 1998. Michigan State University website. http://www.poems.msu.edu/infomastery/default.htm. Accessed March 21, 2008.

3. Field MJ, Lohr KN, eds. Guidelines for Clinical Practice: From Development to Use. Washington, DC: National Academies Press; 1992.

4. Chalmers TC, Celano P, Sacks HS, et al. Bias in treatment assignment in controlled clinical trials. N Engl J Med. 1983;309:1358-1361.

5. Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med. 2001;135:982-989.

6. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA.1995;273:408-412.

7. Moher D, Pham B, Jones A, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet. 1998;352:609-613.

8. Poolman RW, Struijs PA, Krips R, et al. Reporting of outcomes in orthopaedic randomized trials: Does blinding of outcome assessors matter? J Bone Joint Surg Am. 2007;89:550-558.

9. Lachin JM. Statistical considerations in the intent-to-treat principle. Control Clin Trials. 2000;21:167-189.

Ms Strite is principal and managing partner of Delfini Group, LLC, Portland, Oregon. Dr Stuart is president of Delfini Group, LLC, and clinical assistant professor at the University of Washington School of Medicine, Seattle. Mr Urban is president of Solara, Part of CommonHealth, Parsippany, New Jersey.

Disclosure Information: The authors report no financial disclosures as related to products discussed in this article.