A Second Look at the European Randomised Study Of
Screening For Prostate Cancer

Last week, The Lancet published 13-year follow-up results from the European Randomised study of Screening for Prostate Cancer (ERSPC), an international trial of PSA testing in seven countries (the Netherlands, Belgium, Sweden, Finland, Italy, Spain, and Switzerland). (Unfortunately, the complete study is behind a paywall.) The core finding reported was that after 13 years of follow-up, prostate cancer screening cuts deaths by about 20%. However, the investigators concluded that screening should be rejected pending “further quantification of harms,” with their elucidation “a prerequisite for the introduction of population-based screening.” Fair enough.

Even though the results were covered by more than 100 news outlets internationally, absent from the many reports were critical questions about the trial that speak to the trustworthiness of the findings. Study limitations were also given short shrift by the trial investigators and the editorialists.

In proceeding with this story, I learned first hand that even though outsiders reviewing the study pinpointed flaws, they placed near the top praise for the study’s conclusion, that screening be looked at skeptically, based on the knowledge base today.

Here, I take the liberty of sharing the pitfalls, believing that for patients to view screening without bias, honest communication, however complicated, is imperative.

What I learned about the trial sure startled me.

Just Two of Seven Countries Showed a Screening Benefit

Reviewing the trial for PatientPOV.org, Anthony Zietman MD, immediate Past President of the American Society for Radiation Oncology, and Professor of Radiation Oncology at Harvard Medical School, raised this question:

“An unexplained aspect of this multinational study is that the “benefits” of screening were seen in Holland and Sweden, but not in any of the other half dozen European nations contributing patients. Explain that if you can! I know I can’t.”

In an email, Peter Albertsen, MD, Professor of Surgery, University of Connecticut Health Center, Farmington, CT, explained it this way:

“Swedes have a very high incidence of prostate cancer –higher than the rest of Europe and equivalent to US African-Americans. Screening works better the higher the incidence of disease. The Holland study was barely statistically significant. Some have argued that the screen detected cases were treated more aggressively. The big question is Finland. They contributed the most patients, but screening made no difference. They took a population-based approach, rather than Holland that invited men to participate before enrolling them in the study. In all the other countries, the sample sizes were too small. Therefore there was insufficient statistical power.”

American Cancer Society Chief Medical Officer Otis Brawley, MD, amplified issues surrounding the findings in Finland. Like Albertsen, he pointed out that the Finnish component of the trial was negative. “It was the largest part of the trial and Finns have a high rate of prostate cancer as well.”

In addition to the pitfalls noticed above, Brawley said:

Sweden had an unusual non-straightforward randomization that biases toward a finding that screening works. The control group was never informed that they were in a clinical trial. They randomized census rolls. This means that men with metastatic disease at the time of randomization on the screen arm got to opt out, while men in the control arm did not.

Moreover, Brawley questioned whether those in the control arm had the same access to quality of care as the screened arm:

“The screened individuals were treated by experts running the study. The control group got whatever was in the community.”

Brawley considers some of the issues in the trial so troubling that he has called for independent external review of the trial.

Praise for Investigators Opposition to Screening

Opposition to population-based screening has grown in recent years and commentators in this story praised the study’s conclusion as well. In an email, Brawley wrote:

“I agree with that [the conclusion] and it’s consistent with a number of current recommendations, including the American Cancer Society and the US Preventive Services Task Force, which are against ROUTINE screening, but speak positively toward true informed decision-making. The benefits are possible, but are small if they exist, as several studies have shown.”

Albertsen added:

“This study and the recent SPG-4 [Scandinavian Prostate Group 4] results are actually quite consistent.  PSA testing does find some prostate cancers that are eventually fatal.  Radical prostatectomy does cure some prostate cancers that would have been fatal. But in the process of detecting these cancer, a large proportion will not progress, hence overtreatment occurs. In addition, when doctors find very aggressive cancers, they are especially lethal and treatment does not alter outcome. So screening works for some cancers, but not for others.  Now the problem is how to tell these two groups apart.”

Nonetheless, rejection of prostate cancer screening remains a bitter pill for many Americans to swallow. Some question whether they are trading a risk for death from cancer with harms that they think simply don’t compare.

There’s plenty more that has to be done if doctors and patients are going to get on the same page. A lot of work is underway to engage patients, share evidence-based data, and ratchet up understanding of the benefits, risks, and uncertainties.

These are complex issues and they don’t fit well into a simple slogan or headline. In writing posts like this, sharing what I hear patients saying about these issues, I hope to help bridge some of the gaps in understanding, further best care, and set in motion making informed choices.

NOTE: This post is the first of a series. There is a lot to discuss and I am interested in hearing from patients interested in these issues. I’ll try to get the next installment out before my summer vacation, but it may lapse until after Labor Day.

I invite you to comment below, tweet the link to the story, ask me about this on twitter @lauranewmanny, and by all means, like my Facebook page and discuss this there, and/or in comments below . I’d like to engage you all in further discussion.

Meeting Time, Ethical Issues in Psychiatry

I am heading to the annual meeting of the Association of Healthcare Journalists, have been occupied with paying work for a change, and cannot do the usual detailed post I do here. In the meantime, it’s worth flagging some recent health news that patients might want to think about.

Ethical Issues in Psychiatry

Last week, I was proud to post Martha Roberts’ excellent post titled “Mental health medication: is it always A Bad Thing?” She made a persuasive argument for life-saving mental health medications. Too often, anti-psych medication zealots, especially when it comes to psych meds, go overboard in questioning the need for mental health meds. Let’s not throw the baby out with the bath water.

Side Effects (2013) Poster

I’ll admit it is tempting, particularly when you see and recognize #badpharma in regards to clinical trials conduct and safety, psychiatrists’ shilling for the drug companies, and manipulation and release of incomplete data. We’ve seen a lot of this in psychiatry and perhaps because the whole field and medication world revolves around the mind, we find it especially repugnant.

Our antennas go up higher than say, when bad ethics are involved in say, pushing a blockbuster heart failure drug, rheumatoid arthritis biologic drug therapy, or an anti-rejection transplant medication. It’s far easier to relate to a problem with our moods.

A few weeks ago I saw the movie, Side Effects (spoiler alert so don’t look at the link if you plan to see the movie), which I reckon accurately reflects some of the more sinister sides of the pharmaceutical industry in marketing psych drugs and saving its hide. However you feel about the plot line, the psychiatrists in the movie, the pharma folks, and the legal teams, are reprehensible. It’s worth watching.

Then, yesterday, ProPublica released another Dollars for Docs report, implicating psychiatrists more than any other doctor group, spotlighting some who make more than $500K per year in payments from big pharma. People can look up their doctors on the ProPublica site; some may be astounded at the dollars big pharma spends on doctors. Maybe they will look elsewhere.

Surely, these stories are worrisome and things will only change with the public insisting regulators look at this and put policies in place to try to get a grip.

But is that tantamount to all psychiatrists being unethical, psych drugs being thrown at people willy-nilly by anyone you are likely to see, or your very own doctor most certainly being unacceptably on the till, I doubt it. I think we ought to tread very carefully.

What do you think is a reasonable follow-up to this news?

Mental health medication: is it always A Bad Thing?

THIS is a guest post written by Martha Roberts, a journalist and mental health blogger in the UK, who writes the blog, Mentalhealthwise. Martha is on twitter @martharoberts01. Thank you, Martha.

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‘So when can you come off your medication, now you’re feeling so much better?’, someone asked me recently.
‘Well…um, never,’ I replied.
‘It’d be good if you could come off it at some point,’ they said.
‘But I’ll always have bipolar – why would I want to do that?’ I said, trying hard to keep my cool.

I know such questions are asked out of concern and kindness – with a bit of misunderstanding thrown in – but they still get me thinking, ‘Will I always have to explain this?’

pills for bipolar disorder.

pills for bipolar disorder.

Such conversations remind me of how people with conditions like mine (I have mixed affective state, a type of bipolar) still have so much further to go to proper understanding. And one of the big areas that needs to be talked about is medication.

Jennifer Lawrence, who won Best Actress at the Oscars for her role in Silver Linings Playbook (a film about bipolar and mental health), recently said: “It’s just so bizarre how in this world if you have asthma, you take asthma medication. If you have diabetes, you take diabetes medication. But as soon as you have to take medicine for your mind, it’s such a stigma behind it.”

I think I might write this on a postcard, laminate it and dole it out when I’m spent for explanations and ready to tear my hair out.

I think I’ll be handing it out a lot, and it’ll have to be laminated because I’m sure some people will want to tear it up in front of me as I warble on about why I agree with this view. That’s if responses to Rachel Whitehead’s recent article are anything to go by.

Rachel, who works in the Rethink Mental Illness press office, wrote a thought-provoking article in The Independent recently about the demonization of mental health medication.

“What I find worrying,” she says, “is the automatic assumption that a rise in prescriptions, or someone taking medication for a number of years, is necessarily A Bad Thing.

“Medication for mental illness can save lives and give people the stability they need to survive. That may be for a few months, it may be years. While no one wants to be on any kind of medication unnecessarily, for some people, it’s the best option.”

It seems her article has opened floodgates, with one person accusing her of proffering a ‘pro disease model and pro the pharmaceutical industry’, saying that psychiatry, which prescribes these drugs, is based on ‘fear, fraud and force’ rather than ‘health or ‘cures”.

However, others agree with her. One says, ‘I’m so fed up [with] the anti-medication brigade out there’ and another concurs, saying, ‘This medication works for me…I have struggled with this diagnosis for the best part of my life and there were many people telling me not to take [it]…It’s easy to talk for those who have no idea of the suffering of the condition.’

I agree with this. I went on meds after years of ‘talking therapies’ failed to do the trick. Talking therapies definitely have their place – few people seem to dispute that. But drugs have their place, too.

For me, these drugs have been truly health-restoring and life-changing. Of course, these are my views and my experiences. I completely accept that others probably have different ones.

However, it seems to me that if mental health drugs work for you it’s verboden to say so. I want to challenge that (and no, I am not being funded by the pharmaceutical industry) – the enduring view that psychiatric drugs are all ‘bad’ is the stuff that stigma is made of.

It seems it’s permissible to stand up and say, ‘These drugs gave me hideous side-effects and didn’t work for me’, but somehow contemptible and collusive (and suggestive of being ‘in the hands’ of the pharmaceutical companies) to say the opposite, to say, ‘They really helped’.

Why not be allowed to say medication has worked for you without it being implied you’re some kind of misguided prescription junkie?

Listen, I’m not saying mental health drugs are always appropriate – for example, they may be more helpful where there’s a clearcut biological basis like bipolar or psychosis than for other mental health issues.

And I’m not saying my drugs are perfect. How can they be? I would imagine there are very few drugs that have no side-effects. Mine have plenty.

For starters, I now live a ‘Cinderella life’. Every day at 7pm, without fail, an alarm goes off on my mobile and the word ‘Meds’ flashes up, and I know that within two hours of taking said medication, I have to drop what I’m doing and run before I hit the decks (the drugs make me so drowsy you could poke me in the eye with a stick and I think I’d just roll over and snore).

If friends say, ‘Let’s meet up’, I’ll generally vote for an early rendezvous (note: mornings and afternoons are great…). If I take my drugs any later, I get a supreme ‘hangover’ the next day and feel like I’m wading through treacle until sunset allows me to sleep again.

I recently read that Carrie Fisher, actress and fellow bipolar gal, said of her daily drugs regime: “This constantly puts me in touch with the illness I have. I’m never quite allowed to be free of that for a day.”

This is how I feel, too. No matter what I’m doing, no matter how ‘normal’ the task or action I’m in the middle of, the alarm is like a bump back down to earth, reminding me that there’s something different about how I now live my life.

If I don’t take the drugs at all, I feel fine (presumably they have a half-life) but immediately have a shocking night’s sleep where my mind races and my fingers fidget with imaginary touch-typing or piano-playing. In other words, how it always was before meds.

I then worry this will set me on track for what I call a bipolar depressive ‘wobble’ (my drugs have also made me realise how I spent years sleeping fitfully, despite regular attempts at ‘sleep hygiene’).

The drugs also mean I’ve put on a bit of weight, and I can’t drink, smoke or have caffeine. I have to have quarterly ECGs because the drugs could cause prolonged QT intervals in my heart which could lead to my heart just stopping. I also have to have regular blood tests because the drugs are known to raise blood cholesterol which could put me at risk of heart disease. Oh, and I may get cataracts. Great.

I guess this is where the pharma critics find their fodder – ‘How can it be good that this woman is subject to all these side-effects?!’ I understand the anxiety. I also understand that prescribing can be about trial and error, and I can see why people – doctors as well as patients – find this unacceptable.

It’s true to say, too, that psychiatric meds have acquired something of a bad reputation over the years, partly due, it’s true, to inappropriate or indiscriminate use; for example, mass use of benzodiazepines in the 1970s, leading to addiction. Many people also feel that ADHD medications have been over-used in children, especially in the US.

As Dr Ian Drever, consultant psychiatrist at The Priory Woking, tells me: “In time-pressured NHS environments, prescribing a medication may be an easier and more readily-available solution than providing long-term and resource-heavy psychological work. So against that background, it’s possible to see how many people are wary of medication, and see any proponents of medication as being ‘in the pocket’ of big pharma.”

Last year Dr Ben Goldacre, author of The Guardian’s ‘Bad Science’ column, published Bad Pharma, a book in which he describes how there are serious ongoing problems in the pharmaceutical industry, in particular with clinical trials. He says important information from them is still being withheld from doctors and patients and that patients experience avoidable suffering and death as a consequence.

It goes without saying that this needs to change. Thank goodness Ben Goldacre, with his influential voice and dogged determination, is campaigning to do something about it.

But whilst it appears that challenging pharma companies in this way is vital for patient health and safety, it shouldn’t detract from the fact that some people, like me, appear to need medication and seem to benefit from it greatly.

I acknowledge that I was lucky that I found a medication and dose that appears to work for me pretty much straight away (I know many others aren’t so fortunate and take forever to get there, if at all). I’m also aware that the side-effects may come back to bite me in years to come.

In an ideal world it would be marvellous to find a drug that was side-effect free. And maybe, over the next few years, with more R&D by pharma companies who are well-placed to fund this, I may end up with one.

In the meantime, I feel it’s important to acknowledge, where appropriate, that for some people like me the drugs have affected me positively, too.

Before the drugs, I was up and down within the same day, or more precisely, within the same minute within the same hour within the same day. Mostly I was hideously depressed. I was sick and sad whilst also trying to mother, to work, to be a friend and to deal with difficult times. I feel I barely managed it. I don’t think it’s any exaggeration to say I felt like I was hurtling towards my own demise because I felt so unable to function effectively. I felt fractured and with no way of getting fixed, no matter how hard I tried.

And so, I may now be at risk of living a shorter life because of heart problems or other iatrogenic issues, but I’m hoping I’ll live longer than I would have done before meds because I am no longer feeling ill and broken.

It also means that I am better able to utilise therapy appointments because they are now constructive, working towards better ways of managing my condition – before, they were more about crisis intervention, with little space for true change.

Dr Drever, who specialises in depression, anxiety and addictions, says medication can “help to improve mood, or diminish anxiety, thus creating a foundation on which the psychological work can take place to maximum effect.” I agree – my meds and talking therapies are something of a ‘team’, facilitating wellness where talking alone was unsuccessful.

Even my daily 7pm alarm cry has started to become a welcomed interruption. It may be a reminder of my illness but it’s also a reminder of my wellness. It is constant proof that I have a diagnosis and am able to do something about it.

I’m actually one of the lucky ones, not a ‘poor sod’ who has been ‘dumped on medication’. I now have more constancy and stability in my life as a result of medication. In Rachel Whitehead’s words, meds for me haven’t been A Bad Thing.

If more people realised that they might just be a good thing, then maybe people would feel less freaked out by them and the stigma would start to fall away.

Now, where’s my laminating machine? I think I’m going to be busy…

Writing About Alzheimer’s and Dementia Gets Complicated

Now that I have spent three days listening to expert neurologists, demographers, caregivers, and policy people talk about Alzheimer’s, I come away from the meeting with a sense that the story is complicated, and that I hope it is not reduced to talking points and sound bites. I didn’t feel that it was at the meeting, but I can see how reporting could go awry, and not really help readers or society out.

I don’t want to cover Alzheimer’s disease pursuing the “awareness” route, namely pressing how many millions of Americans have the disease, and how unabated, with the graying of America, these numbers will rise astronomically. There is no cure for Alzheimer’s disease. Existing drugs are not all that beneficial, and when they help alleviate symptoms, it seems to be for a very brief window, in a subset of patients, that nobody has convinced me you can predict. Are we at square one? Should we grab at any way to mobilize the troops for the disease?

There’s more negative news: clinical trials for years have been negative and clinical trial enrollment is poor. Can it be improved? Should I promote enrollment in clinical trials? What might a patient gain from participating in a clinical trial? What about informed consent? How do patients with Alzheimer’s disease give informed consent?

Is using amyloid as a biomarker something that should be abandoned because reductions in amyloid have not shown improvements in the disease? What is the state of the science?

What about labeling patients with mild cognitive impairment or Alzheimer’s? Is mild cognitive impairment an entity that is meaningful, or should it be discarded? Some speakers at the Alzheimer’s disease forum were skeptical about the classification, which is not used in many parts of the world. Will mini-screens being in primary care offices become popular because experts and advocacy groups say that they will reduce stigma and work effectively? Under what conditions, could Alzheimer’s disease be overdiagnosed? Remember, older people are on many medicines, they can have electrolyte problems, hearing problems, and other conditions that could impact on diagnosis.

What kinds of protections are in place for people? There is a big push by pharma and the Alzheimer’s Association to be certain to record an Alzheimer’s disease diagnosis in a medical record. That may seem relatively innocuous for old, retired people, but could some people lose jobs, lose health and long term care benefits, be barred from housing? What is the upside to getting a higher count of Alzheimer’s patients? Do the benefits outweigh the risks?

I also think that battles over Medicare need to be discussed with the possibility that many more Americans are likely to be afflicted with Alzheimer’s. Where will they get care? How do Americans want it to look? Will Alzheimer’s patients be warehoused? Can community programs manage people with end-stage Alzheimer’s?

Should innovative non-drug approaches in the arts be funded more widely? How can we reduce stigma about Alzheimer’s disease? I’d like to know a lot more about what is happening today to people with advanced Alzheimer’s disease. Can they find placements? Where? What are equitable ways to fund Alzheimer’s and dementia care?

Long Term Care

How should the country support long-term care? Should children be taught, as they are in lower school, in some parts of Japan, about caregiving, dementia, and Alzheimer’s? What about minorities, lesbian, gay, bisexual, and transgender people with Alzheimer’s? What about aging single people, who are all over America, and growing around the world? What services are available for them? How will we plan for them?

Alzheimer’s disease issues do not exist in a vacuum.

People should be aware of all of these issues, as people think through a national plan for Alzheimer’s disease and think through federal and state policy. I am intrigued that some countries have national plans for Alzheimer’s and I hope to write about them. Perhaps they will be instructive for the US. Far more patient stories need to be told to understand the complexities.