How green is my reformulation?

Recently 6minutes reported that the December issue of Australian Prescriber had been delayed and might be pulped over legal concerns about an article on “evergreening” drug patents.
Evergreening is a drug company strategy which aims to extend patents on popular drugs usually by leaving the active chemical entity essentially intact and fiddling at its edges.
For example, the drug may be altered sufficiently to claim it’s a longer acting preparation, has a different salt or is a superior isomer; perindopril (Coversyl) is a well-publicised example.
Such practices are put under the spotlight in a new market analyst report about ‘reformulation’, which sounds awfully similar to ‘evergreening’.
Compiled by Datamonitor, which claims to be the world’s leading provider of online data and analysis, the report’s press release is titled: “Pharma turns to reformulation to maximize ROI”.
For the uninitiated, ROI stands for ‘return on investment’, and is for any profit-making company a core goal, doctors included.
In what’s hardly a new revelation, the report identifies shrinking drug pipelines as a major threat to pharma profits, in addition to the incursion by generics.
Hence, companies guard their remaining blockbusters zealously, seeking to maximise return on investment.
In an industry where abbreviations and jargon rule, “product lifecycle management (LCM) is an integral part of portfolio continuation and preservation”, the report says, with ‘reformulation’ a common technique to achieve this aim.
“From 2002-2005, 39% of the total product launches from the 50 top manufacturers were reformulations”, according to the report, which outlines four types of the method.
“Switch and grow” is an early to mid-stage strategy whereby patients are “switched from the old to a new and competitively differentiated formulation”, the report says, in turn providing a repositioning of the molecule in the marketplace and an opportunity to grow sales.
A related manoevre, “expand and grow”, apparently involves expanding the scope of the drug by gaining approval for extra indications and growing the market.
Further along in a drug’s life cycle, ‘generic defence’ reformulation becomes relevant, and can provide a chance to switch patients to a new formulation and thereby extend the patent.
Lastly, the “market grab” is a late strategy invoked after a patent’s expiry, where companies develop a reformulation or ‘supergeneric’ that can capture market share from a molecule’s original brand franchise and from other manufacturer’s, including generics”, the report says.
Pfizer’s recent experience with torcetrapib shows the extent of the losses companies face when a drug doesn’t meet expectations, so on one level none of the above should be surprising.
Senior pharmaceutical company executives are merely doing their jobs, trying to maximize ROI.
It just sounds a little crass spelt out so clearly, and when one thinks of how the money might otherwise be spent.

Should I have a mammogram, Doctor?

I’ve always wished there was a simple, definitive answer when women in their forties ask if they should have a mammogram.
But as readers would know, there isn’t.
By my understanding, the closest thing to a correct answer has gone something like this:
“There’s evidence that regular mammography saves lives for women in their fifties and sixties, but we’re not so sure about women in their forties. There’s probably a small benefit, but you have to screen an awful lot of women in their forties to save a life, and on top of that mammography’s thought to cause some breast cancers”.
A study released in the Lancet today was designed specifically to answer this question.
The UK study randomly assigned nearly 170,000 women to an invitation to routine mammography starting at around age 40, or usual care.
After a follow-up of ten years, a small reduction in breast-cancer mortality was shown but failed to reach statistical significance. Over ten years, the absolute risk reduction for breast cancer mortality was 0.40 per 1000 women invited to screening, or in other words 2,512 women needed to be screened for 7 – 9 years to prevent one death over 10 years.
This is a difficult area to study for lots of reasons. For one thing, researchers can only invite women to be screened, not force them. Any study worth its salt will analyse its results on an ‘intention to treat’ basis, and so non-compliance underestimates the effect of mammography. Women in the control group who decide to have a mammogram also dilute the findings.
Furthermore, studies must be huge, and incredibly costly, to have the power to detect small differences. Many, including the Lancet study, fail to recruit the planned number of subjects, thereby reducing the power to detect real differences.
So where do we go from here?
An accompanying editorial says that after ten RCTs of nearly 400,000 women, the current estimate of a small reduction in breast cancer deaths for mammography in this age group is unlikely to change substantially.
Harm, however, must also be factored in, and in this case we’re mainly talking radiation-induced breast cancer, which won’t peak until 10 - 20 years after exposure.
“While the best estimates of harms from screening mammography seem to be less than the benefits, they remain too uncertain to conclude with a high level of confidence that screening mammography in this age-group is associated with a net benefit”, the editorial concludes.
Looks like I won’t be changing my answer any time soon.

Sex with former patients

We’ve probably all heard the expression: “Once a patient, always a patient”.
I’m not sure who lays claim to the aphorism, but its sentiments clearly relate to the power imbalance of the doctor-patient relationship and the inherent inequality of future transactions, whether of a romantic, sexual or financial nature.
An editorial in this week’s BMJ raises the issue of doctors’ relationships with former patients, prompted by new UK guidelines. The author, a medical ethicist, says the new rules wisely avoid a blanket ban on such relationships, which may be ‘vulnerable to a human rights challenge’. Yet, as with the Australian medical board equivalents, the new rules are far from permissive.
For instance, the NSW medical board rightly bans outright relationships with current patients, but its advice on former patients is fuzzier, or in the words of the BMJ editorialist, “an interpretative nightmare”.
According to the board’s website, the “termination of the doctor/patient relationship prior to sexual activity may be raised as a defence”, but its strength will depend on the degree of dependence in the relationship, evidence of exploitation, services provided and the duration of the professional relationship. As well, the time lapsed since the end of the professional relationship would influence the judgement.
It’s not a new question, and as the BMJ author points out, it was in the fourth century BC that Hippocrates said: ‘Into whatever house I enter, I will go into them for the benefit of the sick and will abstain from mischief and corruption and from the seduction of females or males, of freemen or slaves”.
But is this ‘powerful doctor, vulnerable patient’ view out of date, or even paternalistic in these days of patient autonomy and partnership, the editorialist asks?
Not according to the NSW State Medical Board (and presumably other state boards), which says it ‘rejects the view that changing social standards require a less stringent approach’.
But you’ve got to hope logic, rather than dogma, will rule in appropriate circumstances. For instance, a one-off consult for an URTI shouldn’t forever preclude a subsequent relationship between patient and doctor.
If it does, we’re asking unmarried doctors in one-doctor rural towns to sign a vow of chastity, and workforce considerations aside, it just doesn't pass the commonsense test.