NICE against sequential use of TNF blockers for Rheumatoid Arthritis: A payer’s demand for good evidence
Progression of Rheumatoid Arthritis
BBC on NICE Final Appraisal Determination for TNF-alpha inhibitors in RA
My marketing colleagues’ have generally argued that there are limited funds for studies, and such funds ought not be spent studying the competition, unless the plan is to go head to head and whoop some ass. My argument in return has been that clinical trials ought to mirror clinical practice whenever feasible, and clinical practitioners often use drugs in the same class sequentially. The marketing argument is grounded in–duh–marketing principles, and my argument is grounded in evidence-based medicine principles.
UK’s NICE, the advisory group that crafts reimbursement recommendations for the UK National Health Service, has an evidence-based foundation. In their recently completed advisory document (FAD) concerning sequential use of TNF-alpha inhibitors, NICE cites the lack of adequate evidence as paramount to their determination that sequential use of TNF-alpha inhibitors is not warranted:
…Twenty-nine studies were identified that investigated the efficacy of the use of a second TNF-α inhibitor after the first TNF-α inhibitor had failed. Data for one or more specified outcomes (ACR response, DAS28 score, EULAR response and HAQ score change) could be extracted from 19 of these studies, with a further four studies reporting these outcomes for the TNF-α inhibitors as a group rather than for the individual drugs. These 23 studies are reported in the following sections. Only one of the studies [my emphasis] was a randomised controlled trial (RCT). In this study (n = 28), people with an inadequate response to etanercept were randomised to switch to infliximab or to continue with etanercept. The results of the studies could not be combined in meta-analysis. Therefore, only the range of responses observed in studies of a second TNF-α inhibitor is reported in the following clinical effectiveness sections. - NICE FAD, p.8
…The Committee considered that there were limitations to the evidence available for the clinical effectiveness of both TNF-α inhibitors when used sequentially, and alternative treatments such as conventional DMARDs and other biological drugs such as rituximab. The Committee agreed on the importance of further research that examined comparative efficacy of relevant options and that also reflected current best practice in the clinical management of people with RA. The Committee concluded that it would be appropriate to recommend the use of TNF-α inhibitors after failure of a previous TNF-α inhibitor only in the context of research. - NICE FAD p.34
The affected drug companies, patient advocates, and clinical specialists who argued in favor of sequential use, are upset by NICE’s decision. But they shouldn’t blame NICE, and they shouldn’t be surprised by the NICE decision. The only parties responsible for regulator/payer decisions that result from lacking or otherwise inadequate clinical evidence are the research sponsors themselves.
NICE isn’t being unreasonable. It want solid evidence to support sponsors’ claims of efficacy and cost-effectiveness. Good evidence went missing in this case. In the face of inadequate evidence, NICE is justified in using what it (with appropriate consultation) considers to be reasonable assumptions of benefit. End of story for now. The FAD will be reviewed in two years, at which time sponsors will have an opportunity to redeem themselves.
If they aren’t already, drug developers, and I’m including the marketers who increasingly influence clinical-trial design, must view the end game as favorable payment (all forms lumped together as “reimbursement”) for the drugs they’re trying to bring to market. If it’s possible to predict the evidence that will suffice as acceptable to payment decision-makers, and it always should be possible, then it’s also possible to gather the evidence. So, the decision for developers will usually boil down to whether it is worth it to spend the money and time to gather the required evidence. In this case, the sponsors arguably all failed to make the proper decision, or perhaps they simply failed to make a decision at all.
