They were persuaded

In other pharmaceutical news this week, the evidence review committee for NICE (the National Institute for Health and Clinical Excellence) issued a final appraisal determination on the diet drug Acomplia (rimonabant) that surprised the world. It reversed its December draft technology appraisal recommending against the diet drug.

Yesterday, NICE recommended the diet drug become part of UK’s nationalized health coverage and clinical guidelines, going against not only its own earlier decision, but expert reviews and rulings by regulatory agencies from the United States to Europe. While this appraisal determination is not its final formal decision, that’s expected to be released soon.

In its just-released guidance report, Final Appraisal Determination, NICE recommends Acomplia, writing:

Rimonabant, within its licensed indications, is recommended as an adjunct to diet and exercise for adults who are obese or overweight and who have had an inadequate response to, are intolerant of or are contraindicated to orlistat and sibutramine. Rimonabant treatment should be continued beyond 6 months only if the person has lost at least 5% of their initial body weight since starting rimonabant treatment...

The Committee was persuaded to reverse it earlier decision in response to information presented to it by the manufacturer, Sanofi-Aventis, and the testimonies of representatives from various stakeholders, listed at the end of its report.*** NICE said: “The Committee heard from consultees, clinical specialists and patient experts that rimonabant was an important innovation and offered an additional line of treatment.”

Its earlier ruling had concurred with the European Medicines Agency and the Food and Drug Administration Advisory Committee, whose experts were concerned about the drug’s safety and efficacy. The FDA Advisory Committee recently recommended against approval after growing reports of adverse psychiatric reactions. A recent German panel also decided against coverage in that country. Similarly, the earlier NICE draft had not recommended the drug be approved in the UK and had called for more information on its efficacy and safety, as well as its cost effectiveness.

Yet, nowhere in the 28-page report was NICE presented with any new clinical or financial evidence that might support its reversal. In fact, each conclusion it reached, by its own acknowledgement, was the opposite of the data. As the NICE evidence reviewer group wrote:

The manufacturer’s evaluation of the effectiveness of rimonabant focused primarily on the results of four randomised controlled trials. The RCTs showed that rimonabant, as an adjunct to diet and exercise, was associated with a statistically significant greater weight loss than placebo with diet and exercise at 1 and 2 years… After rimonabant treatment was stopped at 1 year, there was a gradual increase in weight until there was no statistically significant difference from placebo at 2 years….

[An extensive review of those clinical trials and the lack of evidence for effectiveness, and the safety issues, is here.]

The NICE committee went on to say it was persuaded that rimonabant, with diet and exercise, was more effective in achieving weight loss than diet and exercise alone, and that “participation in lifestyle and diet and exercise programmes was essential in order to achieve long-term weight loss.” The committee admitted that the evidence from clinical trials showed weight loss was not maintained and that short term weight loss may not have long-term benefits. Yet, the committee was persuaded to approve the drug, saying that “the impact of rimonabant on weight loss and biochemical markers for cardiovascular risk, including those relating to diabetes, was likely to be sustained in the long term.”

The committee specifically discussed the adverse effects of Acomplia, especially related to psychiatric symptoms, and the safety concerns of clinical specialists with the FDA and European Medicines Agency. NICE said these issues were a “significant concern,” but agreed with the representatives who spoke to its committee that screening and monitoring for psychiatric illness and depression could be accomplished through a short questionnaire and tools to identifying pre-existing depression.

NICE, which also assesses the cost-effectiveness of treatments in the UK’s National Health Service, found the manufacturer “significantly underestimated the real costs to the NHS” in its costs estimates, “particularly relating to the long-term effect on cardiovascular disease and diabetes and the costs and quality of life associated with treatment-related depression.” The NICE reviewers felt that the mere 1.5 minutes of doctors’ time the manufacturer assumed would be all that would be needed to monitor patients for psychiatric effects, for example, was unrealistic. Despite these admissions, the NICE committee was persuaded to approve the drug centered on the cost effectiveness model submitted by the drug manufacturer which was based on health risk indices costed out over a lifetime. As the NICE report said:

The manufacturer’s submission included an economic evaluation of rimonabant based on a Markov model. The model evaluated the following treatment comparisons: lifetime treatment with rimonabant plus diet and exercise versus lifetime diet and exercise alone …versus lifetime orlistat plus diet and exercise …versus 1 year of treatment with sibutramine plus diet and exercise.

The [NICE reviewers] considered the economic model structure to be appropriate for the decision problem. In addition, [they] considered the general approach employed by the manufacturer (in the absence of long-term event data) of translating changes in intermediate risk factors to changes in event rates was appropriate for the purpose of estimating lifetime cost effectiveness.

So, unresolved adverse reactions; no proven, sustained clinical benefits for patients; and costs for the public that are likely to surpass all estimates, and NICE was persuaded to reverse its earlier determination to now recommend Acomplia for the treatment of 'overweight' and 'obesity'.

Would you have been persuaded, or do you think other factors may have influenced the NICE decision?

News has reported that not only are representatives of Sanofi-Aventis delighted, but the director of the National Obesity Forum called it excellent news.

*** The sources of evidence (click images to see full-size) that were presented to the NICE committee: