Dissemination and Adoption of Comparative Effectiveness Research Findings When Findings Challenge Current Practices. Conclusions

01/01/2013

Our case study of the CATIE trial highlighted the role of pharmaceutical manufacturers in shaping and reinforcing beliefs about the relative superiority of second-generation antipsychotics, both directly (through marketing and detailing) and indirectly (through key thought leaders), well in advance of the conduct of a CER study. By the time the CATIE results were released, these efforts had succeeded in cementing beliefs about the different classes of antipsychotics, and practice patterns do not appear to have changed in the five years since. Professional societies did not strongly advocate for practice changes based on CATIE’s results (except through an eventual change to guidelines, which appears to have had limited impact). Performance measures were not updated to reflect the trial’s findings and may have continued to reinforce existing prescribing patterns. Professional societies and advocacy organizations challenged the results of the trial in an effort to protect provider autonomy and preserve access to medications, respectively. Public payers were initially unwilling to enact policies that might limit the treatment options of patients with schizophrenia given the relative lack of access to care for this population and the potential backlash from advocacy organizations.

A number of strategies might be used to promote the uptake of results of CER studies similar to CATIE into clinical practice. Methodological choices (such as the exclusion of patients with tardive dyskinesia from the perphenazine group) may limit the perceived generalizability of findings and cause physicians to distrust results. In the case of tardive dyskinesia, providers had strong prior negative experiences involving adverse outcomes. Failure to design a trial to test one of the main beliefs driving use of a treatment meant that an issue important to prescribing providers might be perceived as being inadequately addressed.

Interpretation and formalization of CATIE’s results faced formidable but predictable difficulties given the strength of established beliefs about the efficacy and safety of second-generation antipsychotics. Indeed, it proved very difficult to change the deeply ingrained belief system founded on industry-funded studies. Interestingly, critiques of the study methodology that did not address harms may not have significantly influenced prescribing practices. Likewise, it should be borne in mind that professional societies can be expected to generate guidelines reflecting their professional interests if study results enable such an interpretation by failing to have a clear winner. Timely updates to quality measures that reflect the new CER evidence may prove critical to motivating early changes in practice.

Dissemination and implementation strategies should be vigorous and multiple. Academic detailing within closed systems eventually proved effective in the case of CATIE, but early efforts were constrained by doubts about its value and even a clinical decision support prompt faced initial resistance. Presenting physicians with their actual practice data, which often showed how far they diverged from the ideal, was key to success. Finally, future adverse-event surveillance systems (or registries) may help to resolve lingering questions about relative side-effect risks among patients taking alternative antipsychotics.

Key findings from the CATIE case study are summarized in Table 2.2.

Table 2.2

Key Findings from the CATIE Case Study

Phase

Key Findings

Generation

• The trial design downplayed the risk of tardive dyskinesia (a severe harm) in patients taking the first-generation drug.

• Follow-up may have been too short to capture true side-effect incidence.

• There was a perception that medication dosages did not reflect typical practice.

 

Interpretation

• Prior experience with tardive dyskinesia from first-generation drugs biased practitioners against the CER results.

• Critiques of the study design (later mostly debunked) may have obscured the primary CER result but may not have affected prescriber decisions.

• Widespread belief in the superiority of second-generation drugs (driven by uniformly positive messaging from the pharmaceutical industry) enhanced skepticism of CER results.

• Labeling of drugs as “second-generation” promoted belief in their superiority.

 

Formalization

• Professional society guidelines were driven by a desire to maintain practitioner decisionmaking autonomy.

• Guidelines reflected a concern that payers would limit access to more-expensive medications if the drugs were judged either interchangeable or ineffective.

• Quality measures continued to favor the use of second-generation medications.

 

Dissemination

• Changes in professional-society guidelines (stating that treatments were equivalent) appear to have not significantly affected practice.

• Academic detailing was forestalled by a belief that prescribing patterns were already too entrenched.

• Regulatory and administrative restrictions on industry marketing may have favorably altered prescribing patterns.

 

Implementation

• Advocacy groups and the pharmaceutical industry vigorously opposed any prescribing guidelines interpreted as step-therapy policies.

• Payers nevertheless have increasingly instituted step-therapy guidelines promoting initial treatment with equivalent but less-expensive drugs.

• Medicaid budget cuts may be accelerating a move toward initially prescribing equivalent generic (mostly first-generation) drugs.

• Buy-in usually follows when physicians are presented with actual practice data, which often demonstrate wide divergence from ideal practice.

• The CER results demonstrated the need for practitioners to weigh alternative side effects (e.g., quality of life versus longevity).

 

 

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