And the hepatitis C follies continue...
As we have frequently written,
most recently last week, the
hepatitis C screening and treatment bandwagon keeps rolling along. There is constant public argument about the prices of treatment regimens, which approach $100,000 per patient in the US. However, nearly all the public chatter, which seems mostly to come from corporate public relations people and marketers, investors and investment advisers, physicians with financial conflicts of interest, and pundits with little background in clinical epidemiology, seems never to question the assumption that the new drugs for hepatitis C are miraculous cures, which, of course, makes it hard to argue that they should not cost royal amounts.
The Lack of Good Evidence for the New Hepatitis C Treatments However, starting in March, 2014, we have
posted about the lack of good evidence from clinical research suggesting these drugs are in fact so wondrous. The drugs are now touted as "cures," at least by the drug companies, (look
here), and physicians are urged to do widespread screening to find patients with asymptomatic hepatitis C so they can benefit from early, albeit expensive treatment.
However, as we pointed out (e.g.,
here and
here)
- The best evidence available suggests that most patients with hepatitis C will not go on to have severe complications of the disease (cirrhosis, liver failure, liver cancer), and hence could not benefit much from treatment.
- There is no evidence from randomized controlled trials that treatment prevents most of these severe complications
- There is no clear evidence that "sustained virologic response," (SVR), the surrogate outcome measure promoted by the pharmaceutical industry, means cure.
- While the new drugs are advertised as having fewer adverse effects than older drugs, it is not clear that their benefits, whatever they may be, outweigh their harms.
Furthermore, health care professionals and researchers with heftier credentials in clinical epidemiology and evidence based medicine than mine have since published similar concerns. These included
- a report from the German Institute for Quality and Efficiency in Health Care (the English summary is
here)
- an article in JAMA from the Institute for Clinical and Economic Review (1)
- a report from the Center for Evidence-Based Policy (link
here)
- an article in Prescrire International (2)
These publications and your humble scribe noted that the clinical trials or other types of clinical research about new hepatitis C treatment published in the most prominent journals had numerous methodologic problems that all seemed likely to make the new drugs look better, perhaps intentionally. (See posts
here,
here, and
here.)
Yet the lack of evidence, and the discussion up to last week of this lack of evidence, was mostly anechoic. The public argument continued to be based on the assumption that new treatments of hepatitis C are miraculous.
The BMJ Elicits An Interesting ResponseLast week the British Medical Journal provided the first opportunity for a large audience to be exposed to skepticism about the hepatitis C bandwagon. As we discussed
here, the article by Koretz et al(3) based an affirmation of the four points above on a critical examination of the evidence.
The article, and even our
blog post about it, seem less anechoic than the previous articles and blog posts mentioned above. At least a few commentators were inspired to a defense of the currently received wisdom. However, in my humble opinion, the commentators mainly succeeded in demonstrating how received wisdom is often supported by illogic.
Defending the Received Wisdom with Logical Fallacies - Analysis of an Anonymous Comment Let me start with examples derived from dissecting the arguments of the first anonymous comments we received on our blog post.
Examples of the Straw Man Fallacy The commentators arguments included,
The article suggests that the INF+RBV therapy is just as good as Harvoni,
Note that whether by "the article" the commentator meant the article by Koretz et al,(3) or the
blog post on Health Care Renewal was not clear. In any case, neither made a statement to that effect. Incidentally, I am not aware of any trial that directly compared Harvoni to some combination of interferon and ribavirin.
Both Koretz et al and I did refer to the ONLY trial in which one of the new antiviral drugs (sofosbuvir) was directly compared to peg-interferon and ribavirin.(4) I discussed that trial in detail here ( http://hcrenewal.blogspot.com/2014/04/knee-deep-in-hoopla-triumph-of-medical.html) It showed no significant difference between the sustained viral responses at 12 weeks produced the two regimens. As far as I can tell, there is NO evidence from any controlled trial that the new drugs are more effective than the old drugs.
So the commentator's argument was based on a misstatement of either Koretz and colleagues' or my argument. In any case, it is therefore an example of a logical fallacy, the
straw man fallacy. The commentator was not arguing with something we wrote, but rather a straw man assertion which the commentator constructed.
The commentator also said,
the claim that INF+RBV causes adverse effects in less than 1% of treated is just false,
Again, neither Koretz et al nor I wrote that. So this began another argument based on the straw man logical fallacy.
Koretz et al and I again referred to data from the Lawitz et al controlled trial. That trial did suggest that the new drug produced more, not less severe adverse effects than the old drug.
The Red Herring Fallacy The commentator wrote,
The statement that most patients will not go on to severe liver damage/liver cancer is unproven.
Presumably, this meant most patients with untreated hepatitis C will not go on to severe liver disease/ cancer. This, however, is a statement about the natural history of a disease. How a statement about disease prognosis could be "proven," however, is not clear. It is not ethically easy, or perhaps possible, to do an experiment to prove the natural history of disease. Our knowledge of prognosis therefore relies on observational studies. While such studies can show association, they cannot prove causation. So it is true that the prognosis of hepatitis C is unproven, but in practical terms it cannot be proven, or unproven. While the commentator implied that longer term studies would show that patients have very bad outcomes, but no one knows that with certainty. Thus, the assertion seems to be an example of a
red herring, bringing up an irrelevant point to distract from the issue.
Appeal to AuthorityThe commentator wrote,
SVR12 is a commonly accepted evidence for complete eradication of the virus
So the argument was that some people, perhaps, as was said at the conclusion of �Raiders of the Lost Ark,�
top men believe that SVR means complete cure.
Why anyone believes that SVR12 means cure, and particularly whether this belief is based on evidence and logic was not explained. Just because some people, even top men, believe it does not mean it is true. Thus this assertion is an example of another logical fallacy, an
appeal to authority. By the way, there are plenty of people, including Koretz et al, who do not believe this.
ADDENDUM (27 January, 2015) - I have now independently verified that the comments made on our blog by "anonymous" were made by a patient, and were made honestly, not cynically. Furthermore, English is not the patient's first language, so he or she may have used English words such as "unproven" and "commonly accepted" somewhat differently than I understood.
More Logical Fallacies in the BMJ Rapid ResponsesSimilarly, the article by Koretz et al has generated a few
rapid responses which contain their own share of logical fallacies. Some examples follow from comments through January 19, 2015.
Begging the Question and the Burden of Proof Fallacy In the January 15, 2015 comments by Donna R Cryer
[The article by Koretz et al] severely undervalues the harms, to the individual and society, of active HCV infection. Reduction or avoidance of end stage liver disease or death are not the only appropriate measures of value of screening or the effectiveness of new medications.
Ms Cryer did not state what the values of the harms are, nor what the other appropriate measures might be, and provided no evidence for either assertion. So this boils down to, "you are wrong and I am right." More formally, this could be an example of
begging the question, that is, an argument - in this case that screening is warranted - simply based on assumptions without explanation or supporting evidence. On the other hand, this could also be an argument of the
burden of proof fallacy. Ms Cryer implies that Koretz et al must prove their conclusions, while she simply needs to assert hers.
Appeal to Fear Again from Cryer,
To propose that widespread birth cohort screening efforts be undermined is a disservice to every individual living, unknowingly, with the silently devastating disease that is hepatitis C.
Note that this sentence again appears to include begging the question, with the assertion that hepatitis C is "silently devastating," without explanation or supporting evidence, and the burden of proof fallacy, since it implicitly rejected Koretz and colleagues' argument that hepatitis C is not devastating to all patients, which was based on at least some evidence, without supplying any evidence that it is devastating. Furthermore, this has an element of an
appeal to fear in its use of the emotionally loaded word, "devastating." Note that Koretz et al instead talked about specific complications of hepatitis C.
Wishful Thinking In the January 18, 2015, comments by Nowlan Selvapatt
newer regimes will ultimately improve pricing competition and sustained virologic response rates compared to interferon based therapies.
The author did not explain why these improvements will occur. This could be another example of begging the question. On the other hand, it also could be wishful thinking, which at least some people
consider a logical fallacy as well as a cognitive bias. Obviously, it would be nice for the newer treatments to achieve better results at lower prices in the future, but the future is not so predictable.
An even more explicit example of wishful thinking, alsoby Selvapatt, was,
The hope would be that ... [screening] would serve to reduce the economic and healthcare pressures associated with end stage liver disease caused by hepatitis C.
That would be the hope, certainly, but should the decision to screen be based on hope, or on evidence and logic.
Appeal to Authority In the January 19, 2015, comments by Padmanabhan Badrinath
Regarding side effects Koretz et al state 'However, in a trial of sofosbuvir versus peginterferon plus ribavirin, 3% of participants taking sofosbuvir experienced serious adverse events compared with 1% in the peginterferon plus ribavirin arm (difference not significant)'. According to NICE 'Evidence Review Group (ERG) was satisfied that the evidence showed that treatment with sofosbuvir-based regimens was generally well tolerated and led to fewer adverse events than treatment with peginterferon alfa and ribavirin'.
Note that Koretz et al provided data, and again, that from the only clinical trial that compared a new drug (sofosbuvir) to an old drug, peg-interferon. However, Badrinath contrasted that evidence with conclusions from the NICE report that were about apparently any, rather than just severe adverse events, and Badrinath did not provide any justification of or evidence supporting these conclusions. While NICE is admittedly often considered to be pretty authoritative, simply stating its conclusions in the absence of evidence to refute Koretz's presentation of evidence amounts to an
appeal to authority.
SummarySo it appears that the BMJ article on hepatitis C rendered the skepticism about the miraculous qualities of the innovative new antiviral drugs for hepatitis C less anechoic. However, the response to these echoes seems to have been enriched with illogic.
So it goes in the brave new world of health care. In the current money driven system, new "innovations" touted as miraculous constantly appear. When a few skeptics question the evidence or logic supporting these claims, these doubts usually start as
anechoic. If the doubts are more widely expressed, the first line of defense seems to be often based on
logical fallacies. We most recently
saw such fallacies deployed defending another drug, sacubitril, touted as miraculous from annoying skeptics.
Health care professionals, health care policy makers, and the public at large should not be swayed by illogic. Our continuing series about how
logical fallacies are used to support the status quo and the powers that be in health care suggests, if nothing else, that health care professional education ought to include courses in logic.
References
1. Ollendorf DA, Tice JA et al. The comparative clinical effectiveness and value of simeprevir and sofosbuvir in chronic hepatitis C viral infection. JAMA Inte Med 2014. Link here.
2. Sofosbuvir (Sovaldi), active against hepatitis C virus, but evaluation is incomplete. Prescrire Int 2015; 24: 5- 10. Link here.
3. Koretz RL, Lin KW, Ioannidis JPA, Lenzer J. Is widespread screening for hepatitis C justified? Br Med J 2015; 350: g7809. Link here.
4. Lawitz E, Mangia A, Wyles D et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368: 1878-1887. Link here.
