What Evidence Supports These Remarkable Claims?
The Brennan paper aspired to be a professionalism manifesto, a social-signaling mission document, for academic medical centers. The authors claimed that physicians’ relationships with medical product companies created financial conflicts of interest which “.occur when physicians are tempted to deviate or do deviate from their professional obligations for economic or other personal gain.” Especially toxic was the drug rep practice of reminder-item gifting because it insidiously triggered a powerful but underappreciated psychological impulse to reweigh information and choices in light of the gift.
Gift-exchange theorists make an empirical argument for unconscious reciprocity. They say that getting a recipient to accept small gifts (a pen) is easy because small gift offers trigger nearly hard-wired, reflexive gift acceptance. The icebreaker makes the recipient more willing to accept gifts of increasing value—free travel and expense-paid reimbursement to a product promotion seminar, tuition-free accredited CME, and, ultimately, accepting honoraria for peer-to-peer speaking and well- paid consulting gigs. Imperceptibly, liking, and ever stronger dependency on the gift-giver results. Ultimately, the recipient is “hooked,” and her independent medical judgment is destroyed. Brainwashed by kindness/flattery, the once evidencedemanding, skeptical physician becomes a Manchurian Candidate, not merely for the interests of one pharmaceutical company, but for the industry as a whole (“industry favorable”). Brennan et al. claimed that gifting “often” caused physicians to have positive attitudes toward the reps. They further claimed on Wazana's authority for having found, much more ominously “...an overwhelming majority of interactions had negative results on clinical care.”
What Wazana reported was: “Although some positive outcomes were identified (improved ability to identify the treatment for complicated illnesses), most studies found negative outcomes associated with the interaction. These included an impact on knowledge (inability to identify wrong claims about medication), attitude (positive attitude toward pharmaceutical representatives; awareness, preference, and rapid prescription of a new drug), and behavior (making formulary requests for medications that rarely held important advantages over existing ones; non-rational prescribing behavior; increasing prescription rate; prescribing fewer generic but more expensive, newer medications at no demonstrated advantage.).No study used patient outcome measures” (Wazana 2000: 378, my emphases).
Inability to identify wrong claims about medication reasonably counts as “a negative outcome.” Finding an association between that troubling inability and drug rep exposure cannot rule out that the inability may have been present prior to drug rep exposure. Without more, it cannot be attributed to the drug rep's influence (e.g., gifting reminder items, handing out reprints), even if the inability overlaps with the products in the rep's bag. The inability might (or might not) extend to discern many incorrect medication claims. For example, an early study (Haayer 1982) found that rational prescribing by physicians overall (as judged by an expert panel composed mostly of pharmacologists and pharmacists) occurred less than 50% of the time, irrespective of where their information came from. Indeed, none of the standard professional sources of information seemed to have a great impact on physician prescribing quality.
Developing a positive attitude toward (“liking”) drug reps is not in itself a negative outcome. Here's a plausible justification for it. Suppose physicians appreciated having an increased ability to identify the (correct) treatment of complicated dis- eases—a positive outcome Wazana found associated with rep exposure but not mentioned by Brennan et al. Suppose those physicians attributed (at least some of) that ability to drug rep exposure and were grateful. Their attribution might (or might not) be correct. Their reactive attitude, liking, may (or may not) be well-placed. A study suggesting additional good reasons for positive attitudes toward drug reps will be outlined below.
Awareness and rapid prescribing of a new drug is not necessarily a negative outcome and, to the contrary, is often a positive outcome. Intentionally imposing delay, as has been proposed (Psaty and Burke 2006), denies patients the promised benefits associated with FDA marketing approval (“safe and effective”), which was based on the best-available evidence. How is it rational to withhold use of a newly approved, first-in-class drug that has no alternative (besides doing nothing)? There are risks to doing nothing, also to delay and to too-rapid prescribing of new products. Standing pat with familiar therapeutic options indulges status quo bias (Sunstein 2005) and risks “clinical inertia”—knowing better but not doing better (Phillips et al. 2002).
Status quo deserves no privilege per se. A recent study reviewed original articles published in a high-impact journal over a decade. It found 146 medical practice reversals. The authors concluded that reversal of medical practice is common and occurs across all classes of medical practice (Prasad et al. 2013). A “survival analysis” of clinical practice guidelines found that more than % of the AHRQ guidelines needed updating. It recommended that guidelines should be reassessed for validity every 3 years (Shekelle et al. 2001). A survival analysis of systematic reviews directly relevant to clinical practice found that signals for updating occurred frequently and within a very short time (Shojania et al. 2007).
Newer medications may be better overall than older ones—safer and more effective with more convenient dosing and fewer, less severe side effects. Relationships with industry facilitate the development of these products and the dissemination of information regarding their use (Lichtenberg 2006). A rule of thumb “never be first to adopt nor last” may not pass muster-review with medical “mindfulness”(Epstein 1999) and ill-serve one’s patient. Therapeutic progress requires that somebody go first.
Increased prescription rate may also be questioned as a negative outcome. A review of harm caused by omissions concluded that more harm likely results from omission than commission and our inattentiveness to nonevents blinds us to the risk (Hayward et al. 2005).
A prescribing bias for generic medications may (or may not) be justified. According to FDA, more than 80% of scripts are filled by generics currently. They tend to be less costly than branded “equivalents.” Seventy-eight percent of prescriptions cost patients $10 or less (IMS Health 2014). However, generic sales generate profits for the makers of generics. Generic sales provide larger profit margins for pharmacy companies and pharmacy benefit management companies (PBMs) than branded products. Both pharmacies and PBMs profit from a default rule that presumes equivalence between “in-class” products (generic and branded alike) until proof shows otherwise. Having an interest in setting and applying the standard of proof may have incentive effects. Thus promoters of generics, including “counter- detailers,” promote the interests of companies that make generics, the interests of pharmacies whose profits are larger on generic products and PBMs that negotiate contracts on behalf of employers and patient groups. A Federal Trade Commission analysis of 95 drugs reported that a pharmacy’s gross profits per prescription increase when a first-to-file generic wins 180 days of market exclusivity under an Abbreviated New Drug Application (ANDA). But, a pharmacy’s gross profits per prescription are even higher when an authorized generic (AG) competes with the successful, first-to-file ANDA during the 180 day period. In 2006, Merck decided to sell Zocor to major managed care companies as an AG but to be priced lower that the versions marketed by Teva and Ranbaxy under their FDA-awarded 180 days of exclusivity under first-to-file ANDA. Market price of Simvastatin declined more quickly than it would have without AG. AG competition cost these generic makers millions in revenue, prompting the Generic Pharmaceutical Association to lobby for prohibiting the marketing of AGs.
Prior-authorization and automatic generic substitution rules that defeat “dispense as written” prescriptions also promote the interests of big companies such as CVS Caremark. But those rules also tend to delay discovery of marginal benefit and marginal risk associated with newly approved, branded products. No data say that foregone marginal benefit and delayed risk discovery are opportunity-costs worth paying. Demanding high-quality cost-effectiveness studies, comparing “presumed equivalent” generics, with newly approved drugs and devices serves the financial interests of all those who benefit from status quo bias.
