Interpreting drug company marketing (Proceedings)

Veterinarians in clinical practice use pharmaceutical products as critical components of patient care and well-being. Information about veterinary drugs, both new and old, is presented to practitioners on a daily basis. This information is vital to educated and rational use of drugs as clinical conditions change and new situations arise. However, like any competitive industry, veterinary pharmaceutical companies need to market their products in a manner that will influence consumers (the veterinarian) to use them. Federal agencies place restraints on the claims a company can make about its product, so only certain attributes can be advertised. Regardless, all marketing campaigns will attempt to place their product in the best possible light. Pharmaceutical marketing can come in many forms, be it ads in vet journals, brochures at conferences, or direct meetings with drug company reps. Like any knowledgeable consumer, a veterinarian must be able to look past the "sales pitch" and critically evaluate the product.

The central premise of this topic is illustrated in pharmacology lectures all across North America. Students are asked to learn intricate details about a plethora of drugs, some of which may be "obsolete" by the time they graduate! Many of the drugs they will be using 20 years from now haven't even been developed yet. But how will this veterinarian of the future know which new drug to use? Trial and error? Experienced clinicians face the same dilemma today. A better approach is to give veterinarians a solid understanding of basic pharmacology concepts that will still be relevant long after today's drugs are not! In this manner practitioners can critically analyze new medications and make appropriate choices.

A veterinarian must ask 3 related questions whenever presented with pharmaceutical information:

1. Is this data RELEVANT to the care of my patient?

2. Is this data CREDIBLE to others in the scientific community?

3. Is this treatment APPROPRIATE for this situation?

Relevance to patient care

There are numerous cases of pharmaceutical advertising where the data presented is not relevant to the context to which it is applied.

Efficacy data: When a marketing campaign touts the efficacy of a product, be sure to carefully examine what criteria are used to define efficacy. Sometimes these criteria may not be relevant for predicting CLINICAL success. For example, many antimicrobial drug trials use in vitro experiments as surrogate measures for clinical efficacy. However, there are many reasons why impressive in vitro results may not accurately predict clinical success. % kill in a petri dish is not the same as a clinical cure in a dynamic physiological system! Also be sure to note the conditions under which the experimental data was obtained, and ask yourself if these are realistic. For example, a new macrolide antimicrobial for bovine pneumonia was recently launched, touting its exceptional activity in the lung. This activity is based on a specific in vitro pH medium however, and the drug is much less effective in an acidic environment (possibly like a pneumonic lung?) This doesn't mean the drug will be ineffective for treating pneumonia, but the in vitro conditions were selected to optimize the drug's activity rather than reflect the pathology you are actually treating.

Comparisons to competitors: Many ads will tout the superiority of their product over others, often citing credible literature sources. However, the relevancy of these comparisons can be questionable. In some cases the competitors' products are compounds related or similar to the advertiser's product. For example, some ads will show the superiority of their fluoroquinolone over other fluoroquinolone products. These ads assume that the practitioner only has fluoroquinolones from which to choose an antimicrobial therapy! Another example is a comparison between only COX-2 selective NSAIDs. Could a nonselective COX inhibitor work as well in this case? Or the opposite situation may be presented, where one product is compared against others that are obviously unsuitable for the case presented. Ask yourself (or the drug rep!) why these particular products were chosen for comparison and not others. Remember, a comparison is only going to be made if it makes the advertiser's product look favorable.

Pharmacokinetic and Pharmacodynamic (PK/PD) parameters: Some marketing campaigns describe the PK parameters of their product, such as plasma or tissue drug concentrations (Cp/t), volume of distribution (Vd), elimination half-life (T½elim), or bioavailability (F). These parameters have NO RELAVENCE without a proper physiological context! For example, some ads tout their product's high volume of distribution. Vd is simply a ratio of the drug concentration in the plasma compared to the original dose. There are different categories of Vd, and without a clinical context a high Vd is neither good nor bad. Likewise, some products describe their longer elimination half-life as a benefit. For certain medications in specific circumstances, this may be true. For other products, like concentration-dependent antimicrobials or drugs with narrow therapeutic indices, a long half-life may not be desirable or relevant to predicting clinical efficacy. High drug concentrations in specific tissues may also be presented as beneficial. However, the relative merit of high plasma versus tissue concentrations is still an area of debate among pharmacologists, so don't take plasma or tissue concentrations as an absolute. For example, bacteria in urinary tract infections may be located strictly in the urine or invade the bladder epithelium, as in uropathogenic E. coli. It is likely that both urine and bladder tissue drug concentrations are relevant. Finally, a note about minimum inhibitory concentrations (MICs) of antimicrobials for a particular bacterial species. MIC data by itself is not relevant! An antimicrobial with a lower MIC is not necessarily more efficacious than another antimicrobial with a higher MIC. Predictions of efficacy (and they are just that, predictions!) require knowledge of drug pharmacokinetic properties in relation to the MIC, such as Time > MIC, Cmax/MIC or AUC/MIC. A drug with a lower MIC may also have PK characteristics that make treatment success unlikely.

Credibility of data

Not all information in pharmaceutical advertising is of the same quality! Be sure to examine the sources of the data provided.

Properly performed clinical trials: One of the reasons that pharmaceutical companies rely on in vitro or non-clinical experiments is that properly designed, implemented, and analyzed clinical trials are very difficult to perform. In fact, complete clinical trial analysis is probably beyond the time constraints of most busy veterinarians. However, there are a few quick criteria to check in any clinical trial:

     • Were the samples randomized?

     • Is a control group (placebo or comparison product) used?

     • Were the investigators/clients blinded during the study?

Supporting evidence: Is there any other data in the literature to support the claims of the product? Is all the information presented "company data" or have independent trials been performed? Other trials may provide supporting data that was obtained under different circumstances, or may refute the company's claims. As well, other trials may describe a different indication or dose of a particular compound, or document adverse effects not seen elsewhere. A quick PubMed or VIN search is an efficient way to look for the latest data, and many veterinary/pharmaceutical journals are available online, sometimes for free!

Statistics: This can sometimes be difficult to analyze, but is often essential for determining the credibility of a study's conclusions. Are the results statistically significant? If so, are they clinically significant? (These are NOT the same!) Was an appropriate sample size used? Is there substantial inter- or intra- animal variability in drug concentrations or clinical success? Often the "mean" value is reported in ads, but a wide variability can result in many patients are not receiving optimal drug management.

Appropriateness of treatment

Just because a pharmaceutical advertisement says we CAN treat a condition with a certain drug doesn't necessarily mean we SHOULD treat it that way.

Antimicrobial resistance (AMR): If a marketing campaign is promoting a certain antimicrobial for a specific condition, what do you think are the long-term consequences of this usage in terms of AMR? Some newer antimicrobials are promoting first-line use to reduce chances of "treatment failures", and insinuating damage to the veterinarian's professional image if treatment failure occurs with older antimicrobial usage. This is not a rational method of selecting a proper antimicrobial, and certainly does not consider the importance of AMR!

Cost/benefit analysis: Some products may be advertised as supplemental or accessory medication to along with pre-existing treatment regimens. Is there a therapeutic benefit to be gained by this? If 80% of patients respond favorably to the standard treatment, is it worth adding another medication to increase that number to 90%? Are there increased risks of adverse effects with more drugs, and will client compliance decrease with increased drugs used?

Summary

Several considerations and techniques are discussed for properly evaluating veterinary drug information. Specifically, the relevance, credibility, and appropriateness of the information must be analyzed.

References

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McKellar QA, Sanchez Bruni SF, Jones DG. Pharmacokinetic/pharmacodynamic relationships of antimicrobial drugs used in veterinary medicine. Journal of Veterinary Pharmacology and Therapeutics 2004; 27:503-514.

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