Tag Archives: Ministry of Health

Blocked Bowel

The Press headlines this morning claim the Ministry of Health is blocking bowel screening tests. The article itself states the MoH does “not recommend” use of do-it-yourself bowel screening kits.  I can find no MoH press release relating to these kits, so I am a little confused as to whether or not the MoH is blocking anything at all.  This uncertainty aside, the issue has arisen because of the availability of bowel cancer testing kits which are self administered in the home and made available by the charity and advocacy group Bowel Cancer New Zealand/Beat Bowel Cancer Aotearoa (BBCA). There is evidently frustration within this group with respect to the government’s progress towards a bowel cancer screening program in New Zealand (there is currently a pilot underway).  My interest is not the politics, but merely to inform about the test.

The test being offered as best as I can make out is from Clinical Genomics and is their “ColVantage Home” test.  In the information on their website they give two numbers derived from trials which I believe are critical that any potential user of the test understand before they decide to use the test (indeed, not just for this test).  Those numbers are the sensitivity of the test, given as 86%, and the specificity given at 96-98%.  I expect to most those numbers are meaningless, and even to the scientist they are “minimal” in the sense no indication of how accurate these numbers are given (think “margin of errors” given in political polls).  However, let me take the numbers as gospel and let you know what they mean.

The False Positive.  I'd love to acknowledge the source, but I can't locate them.

The False Negative. I’d love to acknowledge the source, but I can’t locate it.

First, a sensitivity of 86%.  This simply means that for every 100 people who actually have bowel cancer, 86 will test positive with the home kit.  The very very important fact to note here is that a negative test does not mean you definitely do not have bowel cancer.  The 14 missed cases are called False Negatives, or Type II errors and are beautifully illustrated by this classic infographic of the doctor failing to diagnose pregnancy.  My concern with False Negatives and a “home kit” is that some people may feel falsely reassured with a negative test.  On the other hand, a test administered by a medical doctor is not simply the test, but exposure to the doctor who may see other signs or symptoms that the test doesn’t pick up.

 

 

 

False positive

False positive

On the other hand a 96-98% specificity means that for every 100 people who do not have bowel cancer 2 to 4 will test positive.  That is, a positive test does not mean you definitely have bowel cancer. The missed 2 to 4 cases are called False Positives, or Type I errors as illustrated by the diagnosis of the man in the image.

Another way of thinking about this is that all of us before a test have a certain probability of having bowel cancer.  We may get an idea of what that probability is by knowing the rates of bowel cancer amongst people like us.  In New Zealand the rates are very high – some of the highest in the world at about 0.3% or 300 per 100,000 adults.  However, risk is higher as people age, hence screening programs are targeted at older adults (over 50s in this case).  There are other risk factors.  Check out the risk calculator here.  A positive test essentially increases your risk, but not to 100%, and a negative test, decreases it, but not to 0%.  If it was me, and I was worried enough to want to have a test because of increased risk factors, I’d go and ask my GP for one.  On the other hand, if I didn’t want my wife to know (duh!) and got a kit, and it was positive, I’d also head down to the GP.

As I stated before – beware of being falsely reassured by a negative test.  However, there is also a major issue with false positives which bedevil any screening program, and even more so one in which the most at risk population are not being targeted (in this case there is nothing stopping 30 year olds having tests).  This requires a bit of maths.  Let’s pretend for a minute that the tests are only being done by people in a population with a very high prevalence of bowel cancer – say 1%.  That means that for every 10,000 people tested 100 will have bowel cancer for whom 86 the test will be positive.   Of the 9,900 who do not have bowel cancer, 198 to 396 will also test positive – ie falsely positive.  ie, in total, 284 to 480 people will test positive.  ie 22% to 30% of those who test positive actually have bowel cancer.  For the individual who started knowing they had (say) a 1% risk, they now know they have a 22 to 30% risk.  Certainly worth checking out more.

Of course, if people have these tests regularly, the proportion of people who end up having a false positive test at some time will increase (along with the proportion of people with bowel cancer who have a positive test).  ie repeat testing will increase sensitivity and decrease specificity.

Finally, if you have a history of bowel cancer in your family then don’t hesitate to ask your GP for tests and advice on what you can do to minimise your risk through improving your life style.

Major government health directive monitored for efficacy and safety

Last year I was fortunate to become part of a team at Christchurch hospital led by emergency care physician, Dr Martin Than. About 7 years ago in response to some local issues with how patients presenting with chest pain were being evaluated for potential heart attacks, Dr Than began a research program that investigated what clinical, demographic, and biological (blood) factors could best be used to safely and efficiently rule-out a heart attack.

Someone turning up at the doors of the Emergency Department with chest pain desperately wants to hear those reassuring words “You are not having a heart attack.” Unfortunately, for the ED staff this a very difficult conclusion to come to rapidly. As a result, around the world, as many as 90% of patients being assessed for possible heart attack end up being admitted to hospital overnight or longer, although only 20% of them end up being diagnosed with a heart attack. Obviously this is not good for the patient or the hospital – especially given tight budgets and lack of bed space. Dr Than’s work addressed the problem with a large multi-national observational study which assessed if a decision making pathway (called an accelerated diagnostic pathway or ADP for short) could increase the proportion of patients who could potentially not be admitted to hospital instead referred for some outpatient testing(1). This was further refined in another observational study which reduced the number of blood biomarkers that needed testing(2). Finally, and uniquely a randomised controlled trial of the new ADP verse standard practice was run at Christchurch Hospital. This was very successful, nearly doubling the proportion of patients who could be discharged to outpatient care within 6 hours of arriving in the ED(3). More has been done since on refining the ADP … but that is for another post.

The Ministry of Health liked what they saw as did ED physicians and Cardiologists throughout the country. This has resulted in the MOH asking all EDs within New Zealand to implement an accelerated diagnostic protocol. In doing so they will join all of Queensland, and a sprinkling of hospitals throughout the world that have recently adopted an ADP. This kind of positive outcome to local research is what every scientist dreams of, and Dr Than and his team have a right to be proud. But wait, as they say, there is more. Thanks to a Health Innovation Partnership grant from the Health Research Committee we are able to put in place a mechanism to monitor the effect and safety of an ADP at eight hospitals around New Zealand. This is where I come in, as I am collecting, collating and analysing the data for this project.   It is very exciting to be involved not only in helping implement a change of practice, but to be able to assess if that change is effective across a range of New Zealand hospitals from major inner-city hospitals to small rural hospitals, each of which has to adapt an ADP to meet their own particular circumstances. As I write Middlemore, North Shore, Wellington, Hutt Valley, Nelson and Christchurch hospitals all have new ADPs in place. Most if not all EDs will have them by the end of the year.

Some of where accelerated diagnostic pathways have been implemented.

Some of where accelerated diagnostic pathways have been implemented.

The model of observational research -> randomised controlled trial -> local implementation with further research -> mandatory national implementation -> research the effect of that change on local and national levels -> refine processes etc, is I believe a very good one and one that should be standard practice for major health initiatives. The MOH, HRC, and various district health boards that have bought into this process should be commended. There are other similar initiatives happening around the country and a look forward to when as a health consumer I can have confidence in any procedure I may face as been similarly thoroughly assessed.

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Thanks to my Acute Care Fellowship sponsors: Sponsors

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and to the grant funding body:

HRC

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References

  1. Than, M. P., Cullen, L., Reid, C. M., Lim, S. H., Aldous, S., Ardagh, M. W., et al. (2011). A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet, 377(9771), 1077–1084. doi:10.1016/S0140-6736(11)60310-3
  2. Than, M. P., Cullen, L., Aldous, S., Parsonage, W. A., Reid, C. M., Greenslade, J., et al. (2012). 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. Journal of the American College of Cardiology, 59(23), 2091–2098. doi:10.1016/j.jacc.2012.02.035
  3. Than, M. P., Aldous, S., Lord, S. J., Goodacre, S., Frampton, C. M. A., Troughton, R., et al. (2014). A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Internal Medicine, 174(1), 51–58. doi:10.1001/jamainternmed.2013.11362

To PSA or not to PSA

In light of the controversy over the Ministry of Health’s pamphlet on prostate cancer I thought I would repost a post I published in May 2012:

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As a male, 40 mumble years old, do I do it?  Do I get a prostate exam and PSA test?  Do I plan to keep doing tests every few years?

PSA (prostate specific antigen) is a blood test where elevated levels may indicate the presence of prostate cancer.  A powerful group, the US Preventative Services Task Force has come out against screening with PSA giving the test its lowest (D) grade.  They conclude “that many men are harmed as a result of prostate cancer screening and few, if any, benefit.”  Strong words. TV3 (misleadingly, but that’s another story!) and other media reported on this last night. The response of the Urological Society (at least its president) is to reject the report and urges men “not to be deterred” and to “discuss the PSA blood test with their GP.

This is approximately how my conversation went a couple of years ago.

GP: We’ll do a PSA test while we are at it.

ME:  Isn’t that a waste of time? Doesn’t it have a lot of false positives?

GP: Yes, but we can monitor for changes.

Hmmm…so it is not just the value of the test, but how it changes in time that is important.  A quick check on the internet I find that this is called the PSA “velocity.”  Interestingly in the evidence provided by the US Task Force I can find no mention of PSA velocity.

In the meantime, a quick check on the Canterbury Health Labs web site (see here) tells me that the test has a reference range of 0 to 4.0 ug/L (this is a concentration in plasma).  If a test is above this range a GP is likely to want to discuss it with you and may recommend a biopsy.

This is where life gets interesting.  A couple of weeks ago I talked of “False Positives” and introduced the diagram below.  A “False Positive” for myself would have been a PSA above 4.0 ug/L which didn’t turn out to be cancer.  The main issue with PSA tests is the high number of False Positives.  The Task Force suggested that in a screening regime after 3 or 4 tests (over several years) 12 to 13% of participants have a positive test.  Most, though, are False Positives.  Approximately 80% of Positive tests are False Positives!  Consider this – if screening happened in NZ and 500,000 men had a test every 5 years then after 15 to 20 years 500,000 * 0.12 *0.8 = 4800 men will have had a False Positive test.  Another 1200 a True Positive test.

Ideally every test result will lie in the dark blue (true negative) or dark red (true positive). In reality, there is always a few false positives and false negatives [A good test would have few (the narrow ellipse), a poor test would have many (broader ellipse)].

Importantly, the Urological Society put it this way “The PSA blood test does not diagnose prostate cancer. But it raises a red flag and identifies those men who need to have prostate cancer excluded through further investigation via a prostate biopsy.”

PSA does not diagnose – this is a very important point that a GP must communicate BEFORE a test is done.  I would be surprised if even 10% of men realize that PSA does not a diagnose.  So what happens to all the False Positives and True Positives?  This is what the Task Force focused on.

First they asked “Does PSA-Based Screening Decrease Prostate Cancer–Specific or All-Cause Mortality? Does PSA-Based Screening Decrease Prostate Cancer–Specific or All-Cause Mortality?

There was no clear evidence it does (contradictory studies).  In their useful “stats at a glance” publication they state “1 man in 1,000 – at most – avoids death from prostate cancer because of screening.”

If this is so, then it could be worth it (by the way – at a cost of $11.92 + GST + cost of GP visit – say $60 (low), then I estimate screening of 100,000 men a year would cost a minimum of $7.2M annually in NZ).

It is the next questions of the Task Force that are revealing.  The looked at the harms of screening.  The harms of those with Positive test (True or False) and then the harm to those finally diagnosed with prostate cancer.  Again the summary is revealing:

Most prostate cancers found by PSA screening are slow growing, not life threatening, and will not cause a man any harm during his lifetime. However, there is currently no way to determine which cancers are likely to threaten a man’s health and which will not. As a result, almost all men with PSA-detected prostate cancer opt to receive treatment. In addition to the frequent complications of biopsy that lead to a cancer diagnosis, there can be serious harms from treatment of screen-detected prostate cancer.

For every 1,000 men who are screened with the PSA test:

  • 30 to 40 men will develop erectile dysfunction or urinary incontinence due to treatment
  • 2 men will experience a serious cardiovascular event, such as a heart attack, due to treatment
  • 1 man will develop a serious blood clot in his leg or lungs due to treatment 


For every 3,000 men who are screened with the PSA test:

  • 1 man will die due to complications from surgical treatment

And they did not attempt to assess social or psychological harm!  Imagine the conversation at home:

Man: Hi honey, I’m home.  I got a positive PSA test today.

Woman:  That’s nice dear.  Did you get an appointment for a biopsy.

Man:  Yes, in 3 months time.

Woman: Great.  Shall we go out for dinner?

Somehow, I don’t think it would be like that, except perhaps the waiting time for a next appointment.

So where does this leave us.  My opinion, for what it is worth, is that:

  1. A PSA screening program should not take place in New Zealand.
  2. GPs should use PSA tests only where there are other risk factors
  3. Prior to any other procedure, repeat tests of positives should be done under strict conditions. Particularly the diet of the person involved should be changed to minimize the risk of false positives (there is still debate about the role of diet in false positives – so some research should be done at the same time: “Does changing diet change PSA levels in the short term?”).  Men – you can ask for this!
  4. GPs should explain that:
  •            a positive test does not mean cancer (most probably already do explain this, but it worth emphasizing),
  •            there are risks with biopsies, and
  •            there are great risks with treatment (prostectomy or radiation normally).

I qualify this with what appears to me to be a lack of assessment of the benefit of “changes in PSA” levels.  The sort of question which comes to mind is “How accurate is the diagnosis of a 2 ug/L or 100% increase (say) in PSA over 5 years?”

I wonder, would you have a PSA test?