Friday, June 20, 2014

Fourth Time is the (Anti)Charm? - UK NICE Highlights "Uncertainties in the Evidence Base" About Sovaldi

As we have discussed, (here, here and here), while anger continues to build about the $1000/ pill price sought by Gilead for its new antiviral drug for hepatitis C, Sovaldi (sofosbuvir), almost all public discussion still treats the drug as miraculous.  However, my reading of some key trials, and reviews by three groups of evidence-based medicine experts, suggested that the evidence supporting the drug is actually weak and unclear, and hardly suggests it is miraculous.

NICE Weighs In

Now, as first noted by the indomitable Ed Silverman in his revived PharmaLot blog, the National Institute for Health and Care Excellence in the UK is also skeptical.   

the U.K.’s National Institute for Health and Care Excellence, otherwise known as NICE, has declined to endorse the use of Sovaldi, at least for now, until Gilead supplies further evidence of the medication works in certain subgroups of patients. In announcing the move, NICE officials wrote there are 'substantial uncertainties' in the evidence from the drug maker. In a statement issued about a draft guidance, NICE wrote that the agency 'is minded not to recommend' that the U.K.’s National Health Service cover the cost of Sovaldi,

The actual statement said,

 The available evidence shows that sofosbuvir is an effective treatment for chronic hepatitis C in certain patients. However, evidence is lacking for some subgroups of patients with chronic hepatitis C, and there are also substantial uncertainties in the evidence base presented by the manufacturer. The Committee has therefore requested further information from the manufacturer before it can decide whether sofosbuvir is a cost-effective use of NHS resources.

In the US, the only other news source that covered the NICE statement was Bloomberg.

The Problems with the Evidence

As we discussed in our previous posts, the problems with the evidence underlying Sovaldi include:
- Lack of a randomized controlled trial comparing Sovaldi to the previously most recommended treatment regimen
- The only trial trial to compare an antiviral regimen containing Sovaldi to one without it  (Sovaldi plus ribavirn versus peg-interferon plus ribavirin) used a lower dose of ribavirin in the comparator regimen, seemingly handicapping it; had a highly selected patient population whose results would be unlikely to generalize to many patients in the real world; had issues with randomization of patients; only assessed short-term "sustained" virologic response, but not any clinical outcomes; even so, did not show that the sofosbuvir containing regimen produced a better SVR than did the comparator; and appeared to show that the sofosbuvir containing regimen produced more severe adverse effects, and perhaps a higher death rate than the comparator regimen
-  So far, the other published trials included one versus placebo, and multiple trials that compared only sofosbuvir containing regimens to each other, and hence were effectively just case series of patients receiving sofosbuvir.  These case-series all had highly selected patient populations results from whom would be unlikely to generalize to real world patients.

The severe problems with the evidence have now also been noted by
-  the German Institute for Quality and Efficiency in Healthcare (IQWiG)
-  the US Institute for Clinical and Economic Review (look here)
-  the US Center for Evidence-Based Policy (look here)
-  the UK National Institute for Health and Care Excellence (NICE)

Summary - Why Does the Evidence, or Lack Thereof, Remain Anechoic?

Yet none of these reviews have gotten any significant attention in the US media or medical and health care literature, and the idea that Sovaldi has hardly been proven to be a miracle drug, or even better than older drugs for hepatitis C has not informed the US debate and the US outrage about its price.  Examples of the most recent outrage include this in Forbes,

A cure for hepatitis C is within reach for 170 million people around the world — thanks to the charitable efforts of poor and sick Americans who are picking up the tab by paying outrageous prices for their own treatment. It’s like Robin Hood in reverse.


It also took a complete lack of self-awareness — and unmitigated gall — to price Sovaldi the way Gilead has.

Furthermore, Democrats in the US House of Representatives are calling for an investigation (which their Republican "colleagues" will doubtless block), according to Bloomberg,

The company 'did not provide a compelling justification for the high price they are charging for most patients,' Waxman and DeGette wrote 

If the price is outrageous for a miracle drug, it would be even more outrageous for a drug that has not been proven to be better than previously available treatments.

The fact that skepticism about all the hype for Sovaldi has hardly touched the public discussion in the US is a prime example that the anechoic effect lives.  (The only skepticism from an expert could [probably only] be found again in PharmaLot, and came from one of the authors of the Center for Evidence Based Policy report [see above]). 

'For most patients with hepatitis C, they have time to make those decisions,' Valerie King, one of the physicians at the center who worked on the Sovaldi review, tells OregonLive. 'I’m certainly not saying that this is a bad drug. I’m just saying that we don’t know that it is a good drug.' [UPDATE: King later called us to say that 'the research hasn't been extensive enough or transparent enough to tell us it is a good drug or bad drug, or has limited application.' This was based solely on assessing clinical research, not cost issue.]

We have endlessly discussed the anechoic effect, that information and ideas that challenge the powers that be in health care, and particularly that challenge the ability of health care leaders and well-connected insiders to personally profit, often to a tremendous extent - the CEO of Gilead, John Martin, was listed by FiercePharma as the eighth highest paid biotech CEO in 2013, with total compensation of $15.45 million, before sales of Sovaldi really increased -  are considered recent unpleasantness that are just not to be discussed.  However, without open honest discussion of truths, however inconvenient or unpleasant, and the ideas that they suggest, health care will continue to degenerate into a plutocratically run, often corrupt swamp with ever increasing costs, and ever worsening access and quality, causing increasing suffering of patients and worsening of public health.

A good place to start true health care reform might be honest discussion of the evidence about sofosbuvir.   

1 comment:

Steve Lucas said...

This is the same marketing plan followed for the HPV vaccine. A small sample tested to a surrogate end point that is then expanded to a population not tested, followed by a mandate. Today we see a HPV test being proposed as part of a woman’s yearly PAP smear with the end of cementing HPV as a major health issue, while not adding any additional health information.

The HPV vaccine was not tested on the younger children in the proposed covered group and knowing that older children will refuse, thus cutting sales, the proposed mandate would assure compliance by parents.

In the hep C case we see proposed mandatory testing that will then lead to mandatory treatment, thus assuring sales of the product. My understanding is that the largest populations of hep C positive individuals are in our jails and prisons thus making a mandate a guaranteed source of income.

In the HPV vaccine situation the small sample size did not cover various sub groups in the world population. My understanding is that India has put a hold on this vaccine due to a genetic marker that increases the risk of very severe adverse reactions.

Mandates and population testing are very dangerous strategies. They become not only fishing expeditions for many doctors, but the cost of testing and follow up treatment may well bankrupt a medical system, all the while enriching the drug companies involved.

Steve Lucas