Does being unconscious mean you should miss out?

The front page of the Herald this morning questions the participation of unconscious patients in clinical trials.

While I understand Auckland Women’s Health Council co-ordinator Lynda Williams unease, I also detected a failure to understand the process of how progress in medicine is made.

First, all research in such cases is approved by ethics committees which include lay people and patient advocates. That is clear in the article. In my experience they are very very thorough at ensuring the best interests of patients are highest priority. Family or whanau consent is almost always required (especially if the research involves an intervention*). These are the same family or whanau who are talking with medical staff and, at times, providing consent for medical interventions.  When a person is vulnerable it is up to all around them to treat them with respect and care.  Offering them, through their family, the opportunity to participate in research is showing respect for them as a valued member of society who is prepared to give in the interests of others.  Indeed, it is a right of the patient, through their family, to be offered such research.

Second, without such research there can be no progress in medical treatment of unconscious critically ill patients. In order to save lives interventions must be made at critical junctures during the progress of a disease, normally at the earliest possible time. It is in the best interests of us all that such research take place. The alternative is to give up hope and allow current mortality rates to remain as they are. I research a disease (Acute Kidney Injury) which affects 1 in 3 people in the Intensive Care Unit and increases their chances of dying about 4 times. There is no treatment and it is devilishly difficult to detect in the early stages. An estimated 2 million a year die because of Acute Kidney Disease. Without the generosity of family and friends allowing trialling of an intervention (always based on years of prior research and judged to be possibly efficacious) there will be no progress and the death toll will remain high. I salute family and patients around the world who have participated in such studies in the past, and will do so in the future.

Disclaimers: 1. I have no knowledge or understanding of the antiobiotic trial under discussion.  2. I have been involved in an intervention study where participants were unconscious at the time consent was obtained.

*Note, there are some circumstances where when minutes count an intervention is required.  Research in these areas is ethically more difficult, but no less necessary.  I welcome public debate in this area.  While ethics committees can deal with ensuring minimisation of harm in such circumstances, we do need to decide as a society what sacrifices of individual rights we should make for the greater good.

A letter for all District Health Board Candidates

Dear District Health Board Candidates

Soon I and thousands like me will cast our votes to choose our District Health Boards.  Given the huge budgets of DHBs and the huge potential to influence health outcomes I want more information from you than a couple of paragraphs I received with the voting packs.  Below are two questions I think are important.  As this is an open letter on a blog site, I invite others to submit their questions too.  I also invite you, the candidates, to state your name, the DHB you are running for and your response to my or other posted questions (ie not just the blurb from your pamphlets).

My questions:

1. What single health intervention do you want to see implemented and what evidence do you have that it would be efficacious?

2. What plans have you for increasing patient participation in research?


Dr John Pickering

Don’t call this scientist soft!

I’m a soft money scientist, not because I’m cuddly (I am), or because I’m an easy mark for a fiver (I’m not), but because my job and my scientific output depend on my ability/luck at raising money.  As my 100th blog post I thought it time to describe this precarious state of affairs, especially as your taxes may be contributing to it.  Also, when the penny dropped with some friends of mine, so did their jaws.

Before I get into the description, let me say this: It is the best of jobs, it is the worst of jobs.  It is a privilege to spend most of my time solving the puzzle that are the diseases I study with the hope of making a difference to patients in the future.  It is appallingly frustrating that I cannot conduct long-term research or even rely on having an income next year because of the continued axe floating a few feet above my cranium.

In New Zealand, at least, scientists come in many flavours.  There is the industrial scientist earning a salary in a company somewhere who will sink or swim along with the fortunes of the company, there are the scientists in Callaghan Innovation, Ag Research, and other government entities that interface between academia, the commercial world, and the provision of scientific services.  I understand they have a variety of funding sources – in recent years the government side of it has moved from project grant based towards more bulk funding.  Given what is happening with Ag Research, I don’t know if that means more secured tenure for these scientists or not … I’ll let them describe their predicament.  Then, in academic institutions, there are the lecturer scientists who both teach and research.  Traditionally the spend their time 40% teaching, 40% researching, 20% in administration, but there are many variations on the theme. Normally, these people have a more-or-less permanent position (at least as long as students keep coming to do the courses they teach).  To get funding for their research (though not their salary unless they want to “buy out” some teaching time) they need to apply for grants.  In my institution, University of Otago Christchurch, most of the teachers are also active senior medical staff with joint appointments with the CDHB.

Then there are the soft-money scientists.  Most PhD students go on to do a 1 or 2 year post-doc (or two) which is funded by a grant that has been obtained by a senior researcher somewhere.  This is “soft-money” – meaning of limited duration and usually directed at a particularly project.  Most post-docs move into lecturing or leave academia.  A few may pick up additional fellowships or join a group which has the funds to employ them.  To continue in their chosen career they must contribute to the gathering of resources (money money money).  They have no training in this, but after the first few grant rejections begin to learn.  They realise they are competing against scientists who are lecturers or in other entities who already have their salaries covered.  However, the first thing they must put on their grant is their own salary + overheads (113% in my institution).  This, of course, limits what they may be able to say they will do in a grant application as they are not able to write into the grant all the expenses they’d like.  This puts them at a competitive disadvantage.  Another source of income for some groups may be commercial.  This may be the testing in their labs of some equipment  or a new product, or some forensic work etc. Not everyone has that option.

My own sojourn has been a little off the beaten path as six years ago at the age of 40 mumble I returned to the scientific fold after 15 years out of it.  My return was funded for two years initially by a Health Research Council Grant (HRC; your tax dollars) and by a private company who had obtained some government funding for development (Syft).  Since then I’ve had grants from the Australia New Zealand Society of Nephrologists (twice :)  ), Lottery Health, University of Otago Research Grant, and the Marsden Foundation.  My current funding till the end of the year is 41% from a Marsden Foundation grant and 59% from the profits of the last project (a commercial one) our lab-based group ran (alas … another long story, there is now no lab-based group).  Having multiple sources of income is not at all unusual for the more senior research scientists.  Indeed, the current funding levels of even the largest of the grants (HRC and Marsden) are not sufficient to fund a full time senior scientist along with all the associated costs of running a larger project (which these are intended for). The application success rates (7%) make it unlikely that anyone, other than in large established groups with broad funding basis whose success breeds grant success (rightly so!), will be able to sustain a long-term career based on grant funding alone.

One source of funding that I’ve not talked about is philanthropy.  This plays a vital, though small, role in New Zealand science.  Most are familiar with the likes of the Heart Foundation or the Cancer Society which take donations and use some of them for research projects.  An intriguing, though seldom visited, new source of funding is so called “crowd sourcing” where someone pitches a project online to raise money – Dr Siouxsie Wiles successfully raised US$4,480 last year doing just that. This, of course, will not sustain a scientist like myself.  What will?  What do you think is reasonable to spend on science and scientists?  How about the same as we spend per classroom?  According to a Principal acquaintance it costs about $17K per pupil p.a. to run a school.  The average class size is about 23 pupils making it a tad under $400K p.a per classroom.  I think what I do has similar value to educating a class full of kids, but right now I’d settle for half the amount.  Governments, of course, must make choices and impose certain limits on spending.  The current NZ government’s moves to increase spend in research are welcome, but this will at best make a small dent in the grant funding success rate.  Individuals with discretionary disposable income, though, may have other priorities.  I believe that for New Zealand to do more than tread water in the scientific world that it will require those individuals who recognise the value of science to be willing to donate substantial amounts towards science, particularly towards supporting scientists (scientists first, projects second). Indeed, for my own growth and survival as a scientist – for me to be able to put the vision I articulated last week into practice, I see that it will only be possible through the generosity of others.

My 10 Commandments of a Data Culture

Thou shalt have no data but ethical data.

Thou shalt protect the identity of thy subjects with all thy heart, soul, mind and body.

Thou shalt back-up.

Thou shalt honour thy data and tell its story, not thy own.

Thou shalt always visualise thy data before testing.

Thou shalt share thy results even if negative.

Thou shalt not torture thy data (but thou may interrogate it).

Thou shalt not bow down to P<0.05 nor claim significance unless it is clinically so.

Thou shalt not present skewed data as mean±SD.

Thou shalt not covet thy neighbour’s P value.

The tao of science missed by National Science Challenges

The challenges are out. The committee has spoken. And now the critics respond.  Word on science street and in the media goes a bit like this:

Brilliant $73M more for science in New Zealand.  Well done Steven Joyce and the National Party.

Lacking in lustre.  These challenges are all a bit predictable. [eg Prof Hendy here]

Damn.  My research does not fit any of the challenges. [eg Dr Wiles here]

I sympathise with each of these opinions.  The National party has set a goal of 0.8 percent of GDP for science.  This is to be applauded. They have chosen a path of narrowing the scope of science to ensure it meets their own ideology of “government’s job is to grow the economy”.  This is reflected in the challenges and the language around them.  For example the challenge “High value nutrition: research to develop high value foods with health benefits” in the Peak Report document states:

There is enormous capacity to leverage both our primary industry and medical research to discover, validate and develop nutritional products with proven health benefits of significant market potential.

Some scientists seem to think that economic goals some how “devalue” science.  I am rather more pragmatic in suggesting that an economic return is an inevitable result of doing science.  The difficulty, though, is that any attempt to pick winners – and that is what the National Science Challenges does, fails to recognise that science at its best is not shackled but free to explore and expand.  Science by its very nature is at a frontier and a journey into lands unknown.  A pathway cannot be chosen for it and any attempt to do so will as often as not go straight past the pot of gold.

The National Science Challenges have been chosen by committee – there are “winners” and “losers” and the result is necessarily bland.  This is inevitable when science is done by committee.  Great science comes from great scientists who are driven to great discoveries.  It is driven by leadership, and leadership never comes from a committee.  On Morning Report this morning the interviewer and Prof Hendy both mentioned the US Space Program as an example of a truly exciting and great science challenge.  That challenge came from a great leader, President Kennedy, and while driven politically, the political goal was the same as the science vision.  Sadly, once the political goal had been reached the politicians turned elsewhere and the science community was left holding on to a few rocks and a vision shattered.

From my perspective what is needed for science in this country even more than challenges is vision and visionaries.  We need to fund scientists first and projects second.  Sadly, we have that priority completely around the wrong way.  Dr Wiles who ironically was one of the faces of science on the television campaign encouraging public submissions on the challenges is disappointed that her area of research, infectious diseases, is not acknowledged in a challenge.  I am disappointed that enthusiastic talented scientists like Dr Wiles are not directly receiving 3, 5, 10 year’s of salary and research cost support from this new money to pursue their vision. It’s not so much the topic of research as the researcher that counts.  I have a challenge for the New Zealand government.  And that is for their science policy to be evidence based (see Grant Jacobs’ blog post).  Part of that puzzle is whether it is best to fund researchers or to fund projects. This is why I say the Challenges have missed the tao of science – they are not in harmony with the way science is really done.  Let us run a trial.  Randomly select ten scientists and fund their salaries and $100K a year and let them pursue whatever they want.  Compare this to the results of randomly selected National Science Challenge funded projects with the same number of scientists involved.  The title of the trial could be “Is picking winners better than letting winners pick?

Happy WKD

I love living in NZ, it enables me to be the first in the world to wish everyone a happy World Kidney Day.  May your kidneys never lack oxygen, be always filtering, and ever distant from the nephrologists biopsy needle!

Let me remind you:

 If it weren’t for your kidneys where would you be

You’d be in the hospital or mortuary

If you didn’t have functioning kidneys

(with apologies to John Clarke)

Better, take a look at this video too (from

This year’s theme for World Kidney Day is “Kidneys for Life: Stop Kidney Attack.”  If you’ve not caught up with my myriad of other posts, Kidney Attack (aka Acute Kidney Injury) is the rapid loss of kidney function and/or structural damage brought about by toxic damage to the kidneys or temporary loss of blood to the kidneys.

This week I published a blank post entitled “A list of effective treatments for Kidney Attack.”  There is no known treatment – merely acute dialysis, a support for the kidneys, not a treatment. There is no treatment because detection is delayed and difficult and because not enough research has been done.

The good news is that I and many others around the world are engaged in finding new ways of detecting this disease.  Before I list some of the good news I want you all to repeat after me “30,000 kidney attacks a year in New Zealand, 1300 deaths.”  If you live out of New Zealand you may say “Two million die of Kidney Attack each year.”  Now tell someone else … anyone … the next person you see (not your boss if you read this at work).  Well done, thank you.

So, for some good news:

Hooray – we have for the first time means of measuring structural damage to the kidneys.  For us, this is the X-ray moment.  Imagine life before the X-ray – all that could be said is that you could no longer bowl a bouncer (throw a curve ball), play the piano, or dance a jig (whatever that is).  In other words, all that could be said was function was lost.  With the X-ray actual injury to the bone could be observed.  Importantly, it could be observed before function was lost permanently.  The measurement of various molecules we make in the urine are to us like the X-ray – they are measures of injury to the kidney (we call them biomarkers).

We are busy investigating how best to use these biomarkers and have been discovering:

  • which are best after Cardiac surgery, Contrast procedures or in the ICU (all risk factors for Kidney Attack),
  • what the optimal timing is for measurement of each biomarker,
  • how to use the biomarkers in Randomised Controlled Trials aimed at testing new treatments,
  • which biomarkers are best for detecting Kidney Attack when someone has additional co-morbidities like sepsis, and
  • which biomarkers add the most value to what we already know and enable the best assessment of risk of poor outcomes.

In the meantime, some of my work has shown how we can better utilise the information we already have with urine output and the mainstay of nephrology, the plasma creatinine measure:

  • the discovery that even when creatinine does not change after Cardiac Arrest there is likely to be Kidney Attack (it had been thought that it was only when creatinine was elevated there was a problem),
  • a combined measurement of plasma & urine creatinine and urine flow rate (called creatinine clearance) over a short period of time in the ICU helps identify Kidney Attack patients otherwise missed,
  • how best to estimate someone’s “normal renal function” so that a judgment can be made if it has recently changed, and
  • how best to utilise creatinine in Randomised Controlled Trials to tell if an intervention is improving kidney function.

All these add up to progress.  My own and my group’s work over the last 6 years has received funding from a number of funders (see logos attached) some of which originate with your tax dollar – hence my commitment to keep the tax payers informed. I am indebted to my boss, Professor Zoltan Endre, not only did her hire me (I think he mistook Physicist to mean Physician!), he has taught me heaps and consequently we have formed a strong collaboration. Our work has also depended on the good staff of Dunedin and Christchurch Hospital ICU’s, Christchurch Emergency Department, and the Canterbury Health Laboratories.  Without the commitment to research these people make, progress would not have been made.  Most important are the patients or their families who have consented for us to take extra samples or enroll them in a trial. The decision to participate is often made at a difficult time – families wrestling with issues of possible death or long term health issues of their loved ones.  I salute them.  I thank them.  New hope, new medicines, new tests, and new procedures are built on the courage and generosity of the patients and families who participate in research.

Sponsors who have provided grants (top row), or run assays (middle row), or provided free accommodation (me!) for the Christchurch Kidney Research Group, University of Otago.

Sponsors who have provided grants (top row), or run assays (middle row), or provided free accommodation (me!) for the Christchurch Kidney Research Group, University of Otago.

2 years on the Papanui campus remembers and celebrates

This post is published at 12:51 February 22 2013 – exactly 2 years to the day from the deadly Christchurch quake and 5.5km from where I was on that day.  This morning I met with a PhD student as she prepares the penultimate version of her thesis.  Two years ago she, I, another PhD student and several others from my research group occupied the “clip on” on the University of Otago Christchurch building above the main entrance of Christchurch Hospital. Less than 24 hours later the Papanui campus was established.  First PhD student was within one month of submission of her thesis.  The first task was to rescue as much of the thesis as we could from USB sticks etc.  Fortunately we managed to put together enough to get on with, and her thesis eventually had a successful outcome.

My OfficeWhen I reflect now, I just got on with what I knew I could do. I left my medical colleagues in the hospital to get on with what they knew best.  I stood outside the hospital main entrance and saw the first casualties being brought in. Once I was sure that my students and colleagues were OK to find their way home, like thousands of others I started walking home to check on my own family.  In the meantime, others worked.  Yesterday I heard Prof Michael Ardagh, head of the Emergency Department, talk about the response of the hospital staff and medical students.  It is a remarkable story – it worked, and lives were saved, because plans were in place.  It worked because the staff put others ahead of themselves.  This was not just the doctors and nurses.  It was the med students who ran errands, the maintenance staff her with ingenuity (story of a truck and syphoning diesel) kept generators running, of blood bank staff in the bowels of the hospital ankle deep in water with intermittent power processing requests from the ED and ICU, of the Canterbury Health Labs who picked up their equipment, recalibrated, and were back on line within 20 minutes.

The Papanui Campus at age 730 days

The Papanui Campus at age 730 days

The University of Otago Christchurch building is now open again.  The students are back, and the labs up and running.  I hope to get an office back sometime in the next month or two.  The scientific community from the universities of Lincoln and Canterbury, and private enterprises like Canterbury Scientific have been fantastic at opening their doors and hosting labs and staff.  Others, like myself, established themselves where they could and got on with what they could.  While there are casualties of the disruption – staff moved on (I no longer have a lab group to work with), studies interrupted (I had a study going in the ED and ICU at the time which was inevitably suspended), and grants not able to be written for lack of staff, pilot data etc, there has also been much success to celebrate.  Not least are two years of teaching which happened at various odd venues around the city including several sporting club rooms.  Prof Christine Winterbourne was awarded the highest scientific award in New Zealand in 2011 – the Rutherford Medal, and there were other awards for Uni Otago Christchurch staff too.  Just this past month some colleagues have received promotions to Professorships – deserved.  Some new research areas have begun, particularly over the health effects of a major disaster. Students have graduated, and many papers have been published (12 & a book chapter for me in the last 2 years :) ).  Plenty to celebrate.

Across the front of the University of Otago Christchurch building are the words “Research Saves Lives.”  Decades of research saved lives on 22 February 2011.  The research in the years since will save lives in the years to come.  Well done colleagues.  Thank you Canterbury for the support.

Lives to be saved on March 14th 2013

Kidney’s are being attacked every day.  Yours could be next.  So common and deadly are kidney attacks that the theme for this year’s World Kidney Day is “Kidneys for Life: Stop Kidney Attack!


Kidney Attack, or as Physicians and scientists call it “Acute Kidney Injury,” is a syndrome which affects several thousand people a year here in New Zealand.  It is notoriously difficult to detect and can be deadly.  For more than 5 years now I have been researching how better to detect, and ultimately to treat, Kidney Attack.  Over the past 12 months I have posted several times about this – here are links to just a few of the previous posts:

There will be more as we lead up to World Kidney Day 2013.

The Hunting of the SNARF

Some of you may know Lewis Carroll’s classic nonsense poem “The hunting of the Snark”.  Eight men set off with a blank map to find the mythical Snark.

 And the Banker, inspired with a courage so new
          It was matter for general remark,
     Rushed madly ahead and was lost to their view
          In his zeal to discover the Snark

Snarks were dangerous creatures, however

 “For, although common Snarks do no manner of harm,
          Yet, I feel it my duty to say,
     Some are Boojums—”

I dwell in a world where inspired by the new many have rushed on ahead to discover the SNARF (SigNals of Acute Renal Failure).  The hunting of the SNARF has followed contours familiarly trodden and graphically illustrated by a Hype cycle(1).

The Hunting of the SNARF

The Hunting of the SNARF: A Hype Cycle of the hunt for the perfect biomarker of Acute Kidney Injury

It was kickstarted by new technologies called proteomics and genomics which gave the hope that soon would be discovered a rapid, accurate, and, most importantly, early biomarker of Acute Renal Failure (later renamed Acute Kidney Injury, AKI).  This was the beginning of the hype that was driven in no small part by some fantastic early results.  A paper published in the Lancet in 2005 was an important driver in the hype that followed(2).  As with many early studies this involved children and cardiac surgery.  Importantly the biomarker involved almost perfectly distinguished between those who had the disease and those who didn’t (ie not false negatives or false positives).  As the field progressed and more and more studies were investigated across a more diverse range of patient groups and potential AKI causes the ability to discriminate between those with and without the disease became much more modest.  It became apparent that one biomarker to rule them all was not going to be the solution – rather a panel of biomarkers whereby the clinician would choose which biomarkers, if any, to use according to the timing and suspected etiology of the renal injury, the baseline renal function and specific illness of the patient.  We do not yet have such a panel, nor have we conducted sufficient investigations to find if an AKI biomarker(s) adds value to what the clinician can already deduce.  That is partly my job and these are the greater challenges that must drive us up the slope of enlightenment to reach the plateau of productivity where finally we may capture the SNARF.

(1)    Jackie Fenn, “When to Leap on the Hype Cycle,” Gartner Group, January 1, 1995

(2)   Mishra J, Dent CL, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365(9466):1231–8.


Colleague Dr Suetonia Palmer just won a prestigious L’Oreal for Women in Science award.  She’s one of my “go to people” for nephrological type questions (ie all the stuff I don’t know).  This award is very well deserved!  The press release on scoop gives all the salient details.  Just let me add my bit.

What impresses me about Suetonia and her work is her attention to detail and her dedication to dig for the truth.  Her work is focussed on systemic reviews with the Cochrane Collaboration.  Quite simply, this is about as good as it gets for evidence based medicne.  Her mission is to gather evidence from multiple trials for a particular treatment or clinical practice and to analyse that evidence in detail to answer the age old question “Does it really work?”  Her focus, of course, is kidney disease.  An example is a meta-analysis of Vitamin D supplementation in Chronic Kidney Disease (1).  Suetonia and colleagues trawled through data from 76 trials, assessed them for quality, and combined the data.  Apparently Vitamin D had been widely used to prevent and treat secondary hyperparathyroidism – a consequence of the failure of the kidney to handle Vitamin D properly. The result was that despite its wide use, the beneficial effects of Vitamin D compounds on patient-level outcomes were unproven.  We all want our doctors to use the best available treatment with the least side-effects, and we don’t want unnecessary (or expensive) treatments.  Suetonia’s work enables that to happen.

Well done Suetonia.

Our Suetonia

1. Palmer SC, McGregor DO, Macaskill P, Craig JC, Elder GJ, Strippoli GFM. Meta-analysis: vitamin D compounds in chronic kidney disease. Ann Intern Med 2007;147(12):840–53.

See more of  Suetonia’s publications at