RCOG endorses biased HT* report.
Authors have links to manufacturers and no expertise in evidence synthesis
The British Menopause Society’s 2013 recommendations on hormone therapy (click here) is biased in favour of the wider prescribing of HT. For example:
Arbitrary limits should not be placed on the duration of usage of HRT; if symptoms persist, the benefits of hormone therapy usually outweigh the risks.
HRT prescribed before the age of 60 has a favourable benefit/risk profile.
Compare this with the UK Medicines and Healthcare Products Regulatory Agency (MHRA)’s current advice:
For all women, the lowest effective dose should be used for the shortest time.
Or the US Federal Drug Administration
If you decide to use hormones, use them at the lowest dose that helps. Also use them for the shortest time that you need them.
The authors choice of references is also biased. For example they cite a press release from the unpublished KEEPS study as suggesting that there is no cardiovascular harm from HT begun soon after the menopause, but fail to mention these two papers in the BMJ and Lancet (click here and here) suggesting an increased cardiovascular risk.
Disappointingly, the Royal College of Obstetricians and Gynaecologists (RCOG) has endorsed this nonsense (click here) without mentioning the authors’ or the society’s conflicts. Perhaps that is because the authors of the report don’t list their conflicts either. So here they are:
Nick Panay, Lead author – consultancy, advisory and honoraria Pfizer, Bayer, Abbott. (click here) plus Baxter, Schering, Eli Lilly, Galen, Janssen Cilag, Merck, Novo Nordisk, Novogen, Organon, Orion, Procter & Gamble, Se-cure, Servier, Shire, Solvay, Storz, and Wyeth (click here).
The trustees and council of the British Menopause Society also include:
Janice Rymer, Organon (click here) and Wyeth, Janssen-Cilag and Pfizer (click here)
John Stevenson Schering Plough, Wyeth/Pfizer, Bayer, Meda and Merck/Theramex. (click here)
John Studd, Procter & Gamble (click here)
David Sturdee, Amgen, Theramex, Procter & Gamble, Wyeth, Bayer Schering and Novo Nordisk. (click here)
There are no published conflicts of interest for the other three authors Haitham Hamoda, Roopen Arya or Michael Savvas. However, none of them have previously performed an evidence-based review.
Naive women who visit the RCOG website in search of advice about HT should be aware that the review they get directed to is written by authors with links to the HT manufacturers who have no experience of evidence synthesis.
The Cochrane Library is a better source of information. Its systematic review of menopausal hormone therapy (HT) and cardiovascular disease (click here) concludes:
Treatment with HT in post-menopausal women for either primary or secondary prevention of CVD events is not effective, and causes an increase in the risk of stroke, and venous thromboembolic events. HT should therefore only be considered for women seeking relief from menopausal symptoms. Short-term HT treatment should be at the lowest effective dose, and used with caution in women with predisposing risk factors for CVD events.
A rather different message!
Jim Thornton
*Hormone replacement therapy (HRT) changed to hormone therapy (HT) Jan 2016
The Day Lou Reed Died
From the New Yorker, November 25, 2013.
Click here for Sad Song
The Day Lou Reed Died
It’s not like his songs are going to simply
evaporate,
but since the news I can’t stop
listening to him
on endless shuffle—familiar, yes, inside
me, yes, which means
I’m alive, or was, depending on when
you read this. Now
a song called “Sad
Song,” the last one on Berlin,
sung now from the other side, just talk,
really, at the beginning, then
the promise
or threat, I’m gonna stop wasting
my time, but what else
are we made of, especially now? A chorus
sings Sad song sad song sad song sad
song. I
knew him better than I knew my own
father, which means
through these songs, which means
not at all. They died on the same day, O
what a perfect day, maybe
at the same moment, maybe
both their bodies are laid out now in
the freezer, maybe side by side, maybe
holding hands, waiting
for the fire or the earthor the man
or the salt—
if I could I’d let birds devour whatever’s left
& carry them into the sky, but all I can do
it seems
is lie on the couch & shiver, pull a coat
over my body as if it were all I had, as if I
were the one sleeping outside, as if it were my
body something was leaving, rising up
from inside me
& the coat could hold it inside
maybe a little longer.
Nick Flynn
Larkin’s animal poems – 6
Laboratory monkeys
Larkin to Monica Jones: “I thought you might like to see this – I don’t know who else will, as it isn’t really publishable […] it was inspired by the photo on The Listener cover a week or so ago of a rhesus monkey & her baby monkey […]. It carried that complete & utter condemnation of the human race monkeys seem to be able to convey. It was accompanied by accounts of fatuous American experiments of taking baby monkeys away from their mothers & noting that they are unhappy.”
Composed between 12 and 24 February 1965, and unpublished in Larkin’s lifetime, this first appeared in Complete Poems (1988), under the title Ape Experiment Room. Archie Burnett argues for the present title.
Presumably risk of libel, rather than quality or subject made it unpublishable. The break between verses, and the diversion about the experimenter’s wife, around which the horror builds, are pure Larkin.
Laboratory monkeys
Buried among white rooms
Whose lights in clusters beam
Like suddenly caused pain,
And where behind rows of mesh
Uneasy shifting resumes
As sterilisers steam
And the routine begins again
Of putting questions to flesh
That no one would think to ask
But a Ph.D. with a beard
And nympho wife who –
wwwwwwwwwwwwwwBut
There, I was saying, are found
The bushy T-shaped mask,
And below, the smaller, eared
Head like a grave nut,
And the arms folded round.
Philip Larkin
Footnote – According to Archie Burnett, The Complete Poems p 634, the experimenter was Dr Harry F Harlow, Director of the Primate Research Laboratory at the University of Wisconsin.
Harlow was a famous experimental psychologist. He is credited by some with re-emphasising the importance of the mother-infant bond against the theories of the behaviourists at the time. Maybe so, but he also seemed to delight in the awful nature of his experiments. See for example, Harlow HF, and Suomi SJ (1971) Social Recovery by Isolation-Reared Monkeys, Proc Natl Acad Sci; 68: 1534–1538 (click here): “By methods dark, dismal and devious we impregnated several of these reluctant females over a period of years”.
He married three times, albeit only two women. First his student, Clara Mears, by whom he had two children. In 1946 he divorced Clara and married another psychologist, Margaret Kuenne, and had two more children. When Margaret died in 1971 he remarried Clara. He died in 1981.
See also Take One Home for the Kiddies here, At Grass here, Myxomatosis here, First Sight here, and Pigeons here.
Doris Lessing quotes
A mixed bag.
“What’s terrible is to pretend that second-rate is first-rate. To pretend that you don’t need love when you do; or you like your work when you know quite well you’re capable of better.” From The Golden Notebook
On feminism: “Contemporary women scream or swoon at the sight of a penis they have not been introduced to, feel demeaned by a suggestive remark and send for a lawyer if a man pays them a compliment.”
On hearing that she had won the Nobel prize for literature. “Oh, Christ! I couldn’t care less.”
On the 9/11 attacks: “September 11 was terrible, but if one goes back over the history of the IRA, what happened to the Americans wasn’t that terrible.”
“I do not think that marriage is one of my talents. I’ve been much happier unmarried than married.”
“Do you know what people really want? Everyone, I mean. Everybody in the world is thinking: I wish there was just one other person I could really talk to, who could really understand me, who’d be kind to me. That’s what people really want, if they’re telling the truth.” From The Golden Notebook
“Very few people really care about freedom, about liberty, about the truth, very few. Very few people have guts, the kind of guts on which a real democracy has to depend. Without people with that sort of guts a free society dies or cannot be born.” From The Golden Notebook.
“There is no doubt fiction makes a better job of the truth.” From Under My Skin.
Future Perfect
By Lia Purpura
This short poem about eternity appears in the New Yorker, 18 November 2013. The punning title sets it up. The final line makes it.
Future Perfect
Where you were
before you were born,
and where you are
when you’re not anymore
might be very close.
Might be the same place,
though neither is
as slippery
as being here but
imagining where
you will have been—
that point where things land,
are finished, over, and
gone but not yet.
by Lia Purpura
Movember Monsense
Prostate cancer screening
It’s not the sanctimonious mateyness or even the facial hair that put’s us off. And the advice to check your testicles for lumps is good – testicular cancer is treatable if caught early, and no harm comes from removing benign lumps down there.
It’s the fretting about prostate cancer (click here). Sure, it’s relatively common, but most cases are in men well over 70, many of whom die with, rather than from, prostate cancer. And is not worth worrying about until you get symptoms, because screening doesn’t work.
Movember’s suggestion that because women get screened for breast cancer, men are missing out by not being screened for prostate cancer is bonkers. The truth is the opposite. Neither screening programme is proven effective and even if they do have a small benefit they are not worth the hassle and the harms. Women are being treated unfairly by being bullied into being screened.
But you don’t have to take my word for it. Click here for a recent editorial from the Cochrane collaboration – no reduction in mortality, despite a big increase in prostate cancer diagnosis and complications of treatment.
By all means grow a moustache, but keep well clear of prostate screening.
Jim Thornton
The REFRAMED trial
Can true believers get at the truth?
The UK Medical Research Council (MRC) is currently spending over £2M on a randomised trial evaluating a newish type of talking therapy, Radically Open Dialectical Behaviour Therapy (RO-DBT), to treat chronic depression.
As you’d expect from the MRC, the trial is well designed. Registered here, participants are allocated at random to either RO-DBT-plus-anti-depressants, or to anti-depressants alone. The sample size is 276, and the primary outcome is the Hamilton Rating Scale.
But there is a problem. The researchers appear to be true believers in the treatment, and since participants know what group they are in, their responses are likely to be influenced by the researchers enthusiasm.
The acronym, REFRAMED, (REFRActory depression – Mechanisms and Evaluation of DBT) should set alarm bells ringing. It implies that the treatment is going to do something dramatic for this tragic group of patients. It might, but it might be ineffective or do harm. That’s why they’re doing a randomised trial
But it gets worse. The trial website (click here), which is designed to identify potential participants and support those who have already joined, is openly biased. Here’s a couple of sentences from the front page:
80% of participants who have completed the DBT treatment say they would recommend the treatment to a friend
66% of participants in the DBT group found the treatment very helpful, and say they have learnt a lot of new skills.
Click on the button to find out more and you come across these participant testimonials:
“I was anxious before the assessment but I was keen to be assessed and really happy to get into the DBT treatment group. I found the assessment very helpful. It was great to talk to someone about my mental health issues. I was happy to spend the length of the time of the assessment to create a clear picture of my health. The assessor was very understanding and made me feel relaxed.”
“DBT has changed my life dramatically. I am no longer depressed and have the ability of choice in my life. Before DBT I was very fixed and was in a deep depression, unable to make the changes I so desperately needed.”
There’s also a link to a radio interview with Thomas R. Lynch, the developer of the therapy and the trial chief investigator, during which two patient testimonies are read out by actors.
“I needed and wanted a dramatic change in my life to pull me out of my depression. If it hadn’t have been as successful, I wouldn’t be here today. I manage my depression well and can see early signs of depression so now I can prevent myself going downhill and use the skills I’ve been taught.
“I’m no longer depressed and have the ability of choice in my life. Before RO-DBT I was very fixed and was in a deep depression and unable to make the changes I so desperately needed.”
The interview ends with Dr Lynch directing potential participants to the trial website.
If someone ran an anti-depressant drug trial this way, telling participants that they were getting the active treatment and giving them testimonies from successfully treated patients we would regard them as charlatans.
Of course a trial of a talking therapy cannot be completely double blind. The therapist knows what treatment they are giving and the patient knows that they are getting talking therapy. But researchers should still try to minimise non treatment-related differences between the groups. Ideally trials like this should be run by neutral researchers. Perhaps it’s too late for that now. but at the very least the biased information should be removed from the website.
This is not some amateur trial being run on a shoestring. The taxpayer is paying £2M. That’s over £7,000 per patient recruited! It should be done right.
Jim Thornton
Another Exeter/Netmums depression trial
Better follow-up, but unregistered again, and too many endpoints
Yesterday (click here) I commented on a postnatal depression trial run with the parenting website Netmums, in which only 1/3 of participants had been evaluated for the primary endpoint, a depression score, and no health events had been reported at all.
The same authors have just reported another trial (click here), also using Netmums. This time participants were pre-evaluated by telephone interview and those with a diagnosis of major depression were randomised to i-BA or treatment as usual. Follow-up was higher; by 26 weeks 31/41 (76%) participants in the intervention group and 28/41 (68%) controls remained.
Again the treatment appeared to work, but again the trial was unregistered. This matters because the authors report multiple endpoints, but readers don’t know which was primary.
There were five separate outcome scores (EPDS, Edinburgh Postnatal Depression Scale; GAD-7, Generalized Anxiety Disorder Screener; WASAS, Work and Social Adjustment, Scale; SPS, Social Provision Scale; PBQ, Postnatal Bonding Questionnaire) plus six healthcare utilisation measures, as well as antidepressant use. Twelve endpoints, each measured twice, at 17 and 26 weeks, makes 24 endpoints! For some raw scores were compared, for others change scores, and some analyses were done with, and some without, adjustment for baseline imbalances.
The 25th outcome was potentially the clinically most important; a “reliable and clinically significant improvement in EPDS” at 17 weeks. In the i-BA group 23/37 reported this v. 10/34 among treatment as usual. The odds ratio after adjustment for baseline imbalance appeared to be statistically significant*. But the authors didn’t define “reliable and clinically significant” improvement. And even if they did, was it the predefined primary endpoint?
Researchers funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research (CLAHRC) should do better.
Jim Thornton
* The text actually reads: “After adjustment for baseline EPDS the odds ratio for a reliable and clinically significant improvement in the treatment group compared with control was 0.26 (95% CI 0.10–0.71)”. This suggests reduced odds of improvement in the treatment group, i.e. the opposite of the raw data. Presumably they meant “… the odds ratio for not having a reliable and clinically significant improvement …”
Lost to follow-up
2/3 participants in a research trial on postnatal depression
This randomised trial of internet-based behavioural activation (i-BA), to treat postnatal depression had some unusual design features. Participants were identified via a parenting website, Netmums, and gave consent, established eligibility and were randomised online. Those who scored 12 or more on the Edinburgh Postnatal Depression Score (EPDS) were allocated at random as follows:
Experimental – Eleven 40-minute sessions of i-BA delivered online over a period of up to 15 weeks, with access to an i-BA specific online chat room,
Control – Treatment as usual, which consisted of access to Netmums general depression chat rooms.
Of 910 participants 464 were allocated to i-BA, and 448 to treatment as usual but, despite reminders, only 181 (39%) of the i-BA group and 162 (36%) of the TAU group completed the primary outcome of EPDS at 15 weeks. Among this group the mean depression score was lower (11 v 14) in the intervention group. The trial was published in J Affective Disorders in October (click here Note added 30/10/2013 – the original link was to another NETMUMs trial by the same authors. Corrected 20.44 GMT) and the university of Exeter has been tweeting about it.
The trial was unregistered, so we have to take on trust that the sample size and primary endpoints were predetermined. More important are the high losses to follow-up. What happened to them? Although participants were asked to provide their GP contact details, we are not told either how many did so, or whether any experienced major harms. In any normal depression trial, of drug treatment let us say, the authors would report suicide attempts and hospital admissions.
The study was approved by the University of Exeter’s research ethics committee, which is not part of the NHS research ethics committee network. It was supported by the National institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research (CLAHRC), who should know better.
This is the second time recently that the University of Exeter has trumpeted the success of their well-meaning but shambolic research (click here).
Jim Thornton
Abortion 2013
Is the argument over?
For years I’ve tried to teach medical students about abortion. Not how to do one, or what the law says, but how to reason about it (click here and succeeding posts).
Twenty five years ago, students were fairly evenly split between pro-life and pro-choice. More recently the pro-lifers have been in the minority; I’ve had to work hard to support their side of the debate. Last week, for the first time ever, not one student out of about 30 admitted to being pro-life. We still had a debate, me against the rest, but a Rubicon had been crossed.
Abortion used to be the area of moral philosophy where consensus, even on how to frame the argument, was impossible. Have we now moved on? Have all intelligent and educated people reached consensus – permissible under a wide range of circumstances? Perhaps it’s time to end my student debates.
Jim Thornton
Ripe-tomato.org 