“Generic HIV drugs
'less effective',” said the BBC headline. The article continued: “Any rise in
the use of cheaper, non-branded HIV drugs could see more patients with
treatment failure, doctors warn.”
This news looked
worrying, and as soon as it was posted on the BBC website, people flagged it up
on social media websites.
In the last issue of
HTU (see The generic generation, HTU
213), we looked at how many people’s HIV drug regimens will probably soon
include cheaper generic versions of some antiretrovirals. Potentially,
first-line regimens may be entirely made up of generic drugs within five years.
We discussed the
cost advantages, but also whether this might reduce the efficacy of people’s
meds. This might happen if, say, a double- or triple-drug fixed-dose
combination (FDC) pill such as Atripla (tenofovir,
FTC and efavirenz) or Kivexa
(abacavir and 3TC) was easier to take than the drugs as separate pills.
We also looked at
whether there might be pressure to substitute a slightly less-effective drug,
available as a generic, for a slightly more effective one that was still
But the BBC report
looked like it was saying generic drugs were worse because they were generics.
This is still a widely held misunderstanding.
In fact, in order to
sell their drugs, generic manufacturers have to show that the active
ingredients in their products are chemically identical to, and reach levels in
the body which are no more than 5% above or below, branded-drug concentrations.
The BBC report
seemed to have found a study that said the opposite. When we looked into it,
study they cited1
– in the prestigious Annals of Internal
Medicine journal – seemed familiar.
We realised we’d
reported on it last summer,
when its lead author Rochelle Walensky, of Harvard Medical School, presented it
at the International AIDS Conference in Washington.
The study did not
say generics were inferior. In fact, the news it gave was almost entirely good.
Using generic HIV drugs would save the US health system nearly a billion
dollars a year.
researchers went further, and this is where the confusion started. They asked:
let’s just suppose that generics are somewhat
inferior. What if adherence is a bit poorer to separate pills? What if 3TC is a
little less potent than FTC? What if people just don’t like getting
So they fed into
their model a worst-case scenario, within the boundaries of what’s at all
likely. What if generic FTC and efavirenz (plus branded tenofovir) were 7% less
potent than the three drugs put together in Atripla?What if the generics failed for one in
20 patients in the first year, rather than one in 40, as is the case with Atripla?
If you made those
assumptions, the mathematical model they used predicted that you’d lose 4.4 months
from the average HIV-positive person’s lifespan. Those 4.4 months were what the
BBC report seized on.
misunderstand mathematical models. We treat them as infallible oracles and then
feel lied to when they turn out to be wrong. But a mathematical model is not
intended to be reality, which is far too complex to model.
tend to confuse input with output, which is what happened here. The BBC report
assumed the reduced effectiveness of generics was a finding, the sausage that
came out of the machine. It wasn’t; it was one of the assumptions used as
input, the meat fed into the mincer.
This wasn’t helped
putting out a press release that made it look as if the lower efficacy of
generics was a finding.
from branded to generic antiretrovirals would place us in the uncomfortable
position of trading some losses of both quality and quantity of life for a
large potential dollar savings,” Walensky is quoted as saying. ‘Would place us’
sounds like a prediction, doesn’t it? Not ‘would place us if our assumptions
turn out to be true’.
The meat in this
case was also of decidedly dodgy quality. There’s only one study referenced in
the paper2 that found better clinical outcomes in people given a
combination pill than separate drugs. The difference was quite significant in
this case, but the study group – homeless people in San Francisco – may have very specific
difficulties with adherence. Other studies reported on aidsmap.com either
found no difference3
in clinical outcomes in people taking more pills or didn’t
take into account the fact
that people on more pills are likely to be on second-line HIV regimens and may
They also cite three
studies suggesting that FTC could be slightly more effective than 3TC, but this
is disputed by a
World Health Organization (WHO) analysis.5
All these factors
could mean that taking people off combination pills could impact on treatment
success, and it’s perfectly valid to calculate what the impact could be. But if
the assumption that using generics might impact on adherence or viral load
doesn’t stand up, then you save your $1 billion with no shortening of life
WHO wrote to the Annals journal, criticising the way the
research was done and adding that adherence was only a problem if all-generic
FDCs were forbidden by patent law. License generic tenofovir, and you solve the
In the end, the BBC
changed its headline to ‘Study questions generic HIV
drug use’, which it did. But
they still write “[Researchers] say, based on modelling and trial data, that
generic medicines may be slightly less effective.”
Enough, still, to
worry some patients who find a generic pill in their clinic prescription. But
like most predictions, it’s dependent on the assumptions we make. Garbage in:
garbage out. As the immortal baseball player Yogi Berra said: “It’s tough to
make predictions, especially about the future.”