Sweet dreams are made of this (Musings on personalized medicine)

Updated : 28 July 2020 (Fixed song's link)

September's blog derives from increased marketing of medical treatments and clinical laboratory tests as personalized medicine tailored to the individual characteristics and needs of each patient. Seems like a great idea, right?  

After all, in the age of 'selfies' it's all about me. 

The title is from a 1983 ditty by the British duo, the Eurythmics (Annie Lennox and David Stewart). 

PERSONALIZED MEDICINE
'Personalized medicine' is a term that drives me nuts.  This April I blogged about molecular blood typing being marketed as personalized medicine:

• While my guitar gently weeps (Musings on the seduction of technology) [Further Reading]

Five years ago I had sniffed its perfumed allure with the blog

• Snip, snip the party's over (Musings on the seductive rise of DNA typing of blood groups) [Further Reading]

WAIT, THERE'S MORE
Now a new variation has arisen, the latest and greatest 'term du jour' ('term d'année?') is Precision Medicine:

• Red blood cell transfusion. Precision vs imprecision medicine  [Further Reading]

One sentence in the article stood out as a red flag:

'Although currently not practical, providing extended antigen matching by molecular techniques to all patients should improve typing accuracy and reduce alloimmunization.'

If past is prologue, even if impractical and relatively expensive, eventually molecular genotyping will be done for all transfusion recipients. After all, who can resist the sales pitch of personalized and precision medicine?

BANDWAGON
Certainly the United States, with its private health care system, cannot resist and has jumped on the bandwagon. Similarly, so has Canada, UK and other industrialized nations. 

As to the developing world, well they're stuck making do with 20^thC medicine, un-personalized and un-precision.

Of course, a genuine case can be made to tailor tests and treatments to individuals, especially those with special needs such as blood group genotyping for sickle cell and thalassemia patients. 

But why the rush to personalized / precision medicine as embodied by molecular blood genotyping? It's likely because of the reasons cited in 'While my guitar gently weeps':

• To be seen as 'with-it' hipsters on DNA's bandwagon vs being old-fogeys who resist change; 
• Way for TM organizations to develop business lines and increase earnings in age of blood conservation; 
• Self-interest for those who specialized in molecular technology; 
• No humans interpreting serologic test results must be safer; 
• High-throughput automation decreases costs by eliminating staff, with their salaries, benefits, and pensions.

Plus it's good for private enterprises that develop and market test systems and health profession leaders who want to be seen as in the real world of business efficiency. 

ANATOMY OF A SALES PITCH 
Today, many businesses promote and sell stuff that we do not  need. The aim is to trick us into thinking we need the latest and greatest. 

Consider Apple's iPhone. The premise is that potential buyers don't even know what they want until Apple tells them. They don't really need to market it because all geeks know they must have one to be part of the in-crowd. 

• It's the same reason why all TM docs know their facilities must do molecular typing.

Apple builds beautiful products and justifies price with features and benefits no one else can match. Whether you need the features is another matter. But once you've seen them, Apple will make you think you do. 

• Similarly, serologic blood typing cannot match molecular typing. Whether you need the benefits of molecular typing is a moot point.

Apple built one of the most hardcore fan bases of any product, called Apple fanboys/fangirls and, before the iPod/iPad/iPhone revolution, macophiles. I was one and would show disdain for Windows every chance I got. 

• Today, molecular red cell genotyping fans abound and can barely suppress a sneer when mentioning serology and immunohematology. The fan base of influential TM leaders is hard to combat and develops a momentum all its own.

It's worth recalling that whether selling an iphone, tablet, used car or botox, a good sales rep will FOCUS ON

1. BENEFITS and VALUE, NOT PRICE
Some examples [My comments]: 

Before molecular genotyping transfusion service labs had to use inefficient, labor-intensive serologic assays. ²

[PL: Red cell serology is passé, based on inefficient testing that costs more because of paying laboratory technologists for their time.]

Now in the 21st century and with the emergence of precision medicine, inexpensive molecular typing paired with powerful bioinformatics has enabled mass-scale red blood cell genotyping. ²

[PL: Get with the 21^stC. Molecular typing is cheap (really?) and it's twinned with bioinformatics. Bioinformatics sounds pretty darn impressive. We've got datasets coming out the wazoo.]

Web-based data storage and analytics are revolutionizing the provision of antigen-negative blood with an efficiency scarcely conceived of just a decade ago. ²

[PL: You'll be on the bleeding edge and very, very efficient. Plus it's analytics, for gawd sake. And 'analytics leverage data in a particular functional process (or application) to enable context-specific insight that is actionable'.  

Wowsa! Leverage,data, process, context-specific, and actionable in the same sentence. I'm in jargon heaven. Gotta love analytics.]

2. EMOTIONS, NOT REASON
Blood incompatibility remains a significant problem with lifelong consequences that adds to the burden of healthcare delivery and may result in life-threatening delays in care.³

If an antigen-negative patient receives blood from an antigen-positive donor, it could trigger an immune reaction, where the blood recipient’s immune system develops antibodies that can attack and reject the donor RBCs.³

[PL: If you buy our product you will prevent the dreaded immune response and save patient lives. You don't wanna kill folks, do you buddy?]

With today’s dual focus on improving health outcomes and lowering healthcare costs, preventing alloimmunization is the ultimate goal in transfusion medicine. Accordingly, a best practice for the hospital or transfusion center is to create a patient phenotype profile with the PreciseType test before a patient receives his or her first-ever transfusion.³

[PL: Do you dig what TM's ultimate goal is? It's about preventing alloimmunization. (Who knew!) Are you into best practices, a thought leader? Because if you are, you better buy our kit right now, before some patient gets immunized!]

NAYSAYERS
There are those who question the orthodoxy of personalized / precision  medicine and caution against potential pitfalls.  Two examples that examine personalized medicine from a broad perspective:

1) 'Why you shouldn't know too much about your own genes.' [Further Reading] Sample quote: 

• Here is the under-appreciated corollary to the new age of personalized medicine: just because you can do a genetic test, doesn't mean you should.

2) Juengst ET, Flatt MA, Settersten RA, Jr. Personalized genomic medicine and the rhetoric of empowerment. Hastings Cent Rep. 2012 Sep-Oct; 42(5): 34­40. [Further Reading¹] Sample quote: 

• 70 million Baby Boomers, now or soon-to-be over age 60, seek to live not just longer, but healthier and more productive lives. 
• When they fully understand and embrace personalized medicine, it will create an unprecedented level of consumer demand. 
• When physicians feel they may incur liability for not offering a test that provides information on optimal care, the impetus toward adoption will be even greater.

LEARNING POINTS
Eventually, everywhere in the developed world, red cell matching of patient and donors will routinely be done by molecular blood typing. It will be precision medicine, personalized medicine done using kits supplied by foreign companies and performed by minimally trained, inexpensive local staff supervised by a well educated lab professional.

If employers plan wisely, staff can be hired part-time or casual so they won't need to worry about benefits and pensions. 

In Canada government health care money will flow abroad, giving sustenance to anonymous investors of Immucor, et al. They'll leverage our health care dollars where they WON'T do the most good for our communities, all in the name of efficiency and safety.

POSTSCRIPT
Am I similar to 19^thC Luddites, protesting against new labour-economizing technologies? Maybe, though I'm not against technology per se and have embraced computers and the Internet from the get-go.

But, hot damn! I'm gonna get my genome profile done because it's all about me. And I can get it done for $199 CDN by 23andme...not that I really want to know.

And if I ever need a blood transfusion, I'm not into being second class and will demand complete molecular antigen typing with donor blood. Not that I'll get it now but definitely one day. None of that passé serology for me!

FOR FUN
A great song, one of my favorites, that highlights the allure of molecular blood typing and personalized / precision medicine. 

• Sweet Dreams [are made of this] (Annie Lennox, Live 8, Hyde Park, London, 2005)

'Sweet dreams are made of this
Who am I to disagree?'

As always, comments are most welcome.

FURTHER READING

1. Juengst ET, Flatt MA, Settersten RA, Jr. Personalized genomic medicine and the rhetoric of empowerment. Hastings Cent Rep. 2012 Sep-Oct; 42(5): 34­40. (Free full text)
2. Klein HG, Flegel WA, Natanson C. Red blood cell transfusion. Precision vs imprecision medicine. JAMA. Pub online 10 Sept. 2015. (Free full text)
3. Immucor: PreciseType™ HEA Test 

Other
Carolyn Johnston. Why you shouldn't know too much about your own genes. (Washington Post, 11 Sept. 2015)

USA FDA: Paving the way for personalized medicine. FDA’s role in a new era of medical product development  

US News & World Report. Personalized medicine

USA White House. Next steps in developing the precision medicine initiative

Prior Related Blogs
While my guitar gently weeps (Musings on the seduction of technology) |  April 2015

Snip, snip the party's over (Musings on the seductive rise of DNA typing of blood groups) | Dec. 2010

While my guitar gently weeps (Musings on the seduction of technology)

Updated: 13 April 2015

April's blog focuses on news items from TraQ's latest newsletter that have a commonality. 

• The main item deals with a molecular assay to identify 35 red cell antigens from 11 blood groups. 
• The other, included to illustrate the blog's theme but mainly here for fun, focuses on the clinical uses of platelet-rich plasma (PRP). 

I'll leave it to readers to ascertain what the stories have in common. The blog's title derives from a 1968 George Harrison ditty in the Beatles 'White Album'. 

 NEWS ITEMS

• Boston Children’s Hospital ends bad blood between donors, patients (24 Mar. 2015)
• Hospitals aim to better match blood donors and recipients (19 Jan. 2015)
• Dubai plastic surgery boom includes PRP facial rejuvenation (6 Apr. 2015)  
• Can PRP penis and vagina injections give a better sex life? (14 Mar. 2015)
• See Further Reading below for more information.

MUSINGS on MOLECULAR BLOOD TYPING 
Typing of blood group antigens at the molecular level has been in the works for years. Now it's moving beyond its original special uses because of technological advances, decreasing costs, and lobbying by vested interests. 

However, its cost-effectiveness is still unproven. Immucor's PreciseType^TM HEA test costs ~$350 USD but that likely varies significantly depending on individual contracts. And any cost study I've read in journals like AABB's Transfusion is so dependent on assumptions as to be almost meaningless and needs to be read carefully and critically.

Also, molecular blood typing is not the be-all, end-all for the 100s of blood group antigens that exist, since not all are DNA-defined. But the list of antigens covered is impressive and includes nearly all clinically important blood group systems (see Further Reading). 

Regardless, molecular blood typing has no end of proponents, mild and strong. For example:

• Joint UK Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee (JPAC) thinks it's inevitable. 
• AABB, on the other hand, perhaps seeing a money-making opportunity for its publications and consultant branch, developed 'Standards for Molecular Testing for Red Cell, Platelet and Neutrophil Antigens'. 
•  AABB actively promotes DNA typing, even to the point of petitioning the US government to fund testing (Nov. 5, 2014). 

I wrote a blog on this topic years ago: 

• Snip, snip the party's over (Dec. 2010) 
• Suggest you read it later, if the mood strikes. My predictions have come true but they were no-brainers. 

Me Medicine

Now molecular blood typing is being marketed as personalised medicine, ie., the tailoring of medical treatment to individual characteristics of each patient. The idea derives from the 13-year, $3 billion Human Genome Project. For example, Immucor advertises PreciseType this way:

• Molecular Technology Personalizes Donor/PatientCompatibility

Makes it seem that anything less is substandard. Get with the program, health care providers, because it's all about me.

But many experts like Donna Dickenson, emeritus professor of medical ethics and humanities at the University of London and research associate at the HeLEX Centre, University of Oxford caution that

• 'Me medicine' could undermine public health measures (New Scientist, Sept. 2013)

MUSINGS: PLATELET-RICH PLASMA (PRP) 

I'd read several news items over the years about PRP's use in orthopedics, particularly for athletes:

• Clinical use of platelet-rich plasma in orthopaedics 

And recently the owner of a local restaurant I frequent mentioned that she had her own plasma injected into her knee but had to pay for it as it wasn't covered by Canada's universal health care system, at least for her. She said her knee caused a lot of pain (she's a 50-something server in the restaurant) but apparently it wasn't bad enough to be operated on yet. 

With that as background, recent news items on PRP's expanding clinical uses caught my attention. Medical tourism grows daily, at least for the rich. Seems Dubai now has more plastic surgeons per capita than any other city in the world and hopes to attract half a million medical tourists by 2020. 

The penis and vagina PRP nonsense was included just for fun. But really, Academy Award nominees got a coupon for a Priapus Shot? You cannot make this stuff up. 

BOTTOM LINE 

Okay, I lied because I'm sure you've gotten the blog's theme by now:

• Where there's a buck to be made or an agenda to be advanced, clinical uses of diagnostic tests and products will inevitably expand well beyond what's evidence-based. 

TM poster-child for phenomenon? Intravenous immunoglobulin (IVIg). 

But what's surprising, at least to me, is how few voices, especially in the TM community, question the *expanded use* of innovations like molecular typing of red blood cell antigens under the guise of me-medicine. Particularly since our so-called 'thought leaders' are so into evidence-based these days. 

I understand why advances that help solve real TM problems are celebrated. But why the uncritical approach? Is it because blood typing at the molecular level is 

• A marvelous innovation and all want to be seen as 'with-it' hipsters on DNA's bandwagon? Versus being old-fogeys who resist change? 
• Way to develop a business line and maximize earnings in a shrinking field like TM in age of 'blood conservation 'über alles', e.g., AABB? 
• Outright self-interest for those who specialized in molecular technology and need to maximize their career's life-span?  
• Seen as eliminating humans from the equation, such as interpreting serological test results, thus must be good? 
• High-throughput automated innovation, another way to decrease costs by eliminating those pesky creatures, aka staff, with their costly salaries, benefits, and pensions? 
• Better to give money to international companies than keep staff, aka tax payers and community builders, employed at home?
• Plus many staff are probably contemplating retirement anyway and eliminating their jobs will help make that decision easier? 
• Viewed as best thing since sliced bread, not just a significant innovation with specific uses, motivating proponents to abandon whatever critical thinking skills they ever had?  

BOTTOM LINE 

Personally, I wholeheartedly agree that molecular blood typing is a useful, indeed marvelous, advancement that will make blood transfusion safer for many. Celebrate its potential but please don't promote it beyond clear clinical uses so that anything else seems sub-standard, as in this over-the-top headline: 

• 'Boston Children’s Hospital ends BAD BLOOD between donors, patients' (Emphasis is mine)

FOR FUN 

'While My Guitar Gently Weeps':

• #136 on Rolling Stone's "The 500 Greatest Songs of All Time"
• #7 on its list of 100 Greatest Guitar Songs of All Time
• #10 on its list of The Beatles 100 Greatest Songs. 

While my guitar gently weeps (Paul McCartney and Eric Clampton tribute to George Harrison, Queen's Golden Jubilee, London 2002) 

I don't know why nobody told you 

How to unfold your love 

I don't know how someone controlled you 

They bought and sold you. 

I look at the world and I notice it's turning 

While my guitar gently weeps 

With every mistake we must surely be learning 

Still my guitar gently weeps 

As always the views are mine alone and comment are most welcome.

FURTHER READING 

References for those who want to delve further into the blog's topics. 

Molecular blood typing

• PreciseType^TM HEA, first blood compatibility molecular assay used in transfusion medicine approved by FDA (Press release, 22 May 2014)
• Immucor's website (See blood group antigens that can be typed)
• Explanation of how PreciseType works
• Molecular typing for red blood cell antigens (AACC's Clin Lab News, 1 Mar. 2015) 

Nice overview: Denomme GA. Prospects for the provision of genotyped blood for transfusion. Brit J Haem 2013 Oct;163(1):3-9.

For molecular blood typing in detail, see these papers from 2009. Info overload but fascinating insight into predicting the future (All papers free full text): 

Molecular blood group diagnostics.Transfus Med Hemother. 2009 Jun; 36(3): 154–155.(editorial) 

Five expert opinions on the question ‘Will genotyping replace serology routine blood grouping in the future?’ 

Interpretations are mine. (Author origins refer to where they worked then, not necessarily nationality.) 

• Opinion 1: Only partly. Unlikely unless... (Germany) 
• Opinion 2: Probably (Switzerland) 
• Opinion 3: For some applications (Austria) 
• Opinion 4: Personalized versus Universal Blood Transfusions – Combining the Efforts: Probably but in combination with enzymatic conversion (ECO) to remove A and B antigens (Sweden) 
• Opinion 5: Yes (Netherlands) 

Platelet-rich Plasma 

• Power of platelets (Nov. 2014) 
• Plasma fraction market - Global industry analysis and forecast 2014-20 (Press release, 6 Apr. 2015) 
• Platelet rich plasma market to treat orthopedic injuries, cosmetic surgeries expected to grow (23 Mar. 2015) 

You don't own me (Musings on TM professionals as industry's poodles)

Updated 1 Nov. 2012

This month's blog is about how much of the TM information we consume is meant to inform, how much is crafted to persuade, and how much info purveyors assume we’re owned by them, i.e., their poodles. The title is from a 1964 Lesley Gore song. 

The blog was stimulated by 3 items:
1. Supposed news from new-medical.net in its 'Insights from industry' section:

• Blood banks: an interview with Celia Tombalakian, Worldwide Group Director, Immunohematology at Johnson & Johnson's Ortho-Clinical Diagnostics, Inc. (OCD) 

2. The article motivated me to visit OCD's 'On Demand' website and register to see its offerings. 

3. Then I was reminded of a recent research paper by OCD staff published in AABB's Transfusion:

• South SF, Casina TS, Li L. Exponential error reduction in pretransfusion testing with automation. Transfusion. 2012 Aug;52(8):81S-87S.

BACKGROUND
Increasingly, I suspect that industry owns the transfusion medicine community. In a way, it's natural given that TM was healthcare but now is business and has been for awhile. Businesses depend on each other to survive. You scratch my back and I’ll scratch yours.

Today's AABB is more and more cosy with commercial interests, which is also natural given the reliance of the former on the latter for advertising revenues and conference support. Plus, as noted in earlier blogs, some AABB luminaries have close ties with industry. It's one big happy family.

The blog’s components  - industry promoting automation via 3 mechanisms - are akin to a full court press in basketball in which industry pressures TM staff from every angle to buy into their false assertions about automation.

The blog's theme is how much industry thinks it owns us and attempts to baffle our brains with BS. 

A common thread in industry’s automation initiative is to create false arguments. For example, manual methods have more processes than automation (true), therefore automated instruments have fewer chances for human errors to occur (true). 

BUT… here’s the logical fallacy (the BS, if you will): Where do most serious TM errors occur? Are they related to manual testing? 

Read and assess for yourself.

1. INTERVIEW
First note where this interview was published: news-medical.net

As with many so-called health sites, news-medical's business model is not immediately apparent without reading the fine print. And let's face it, that's the first thing we do when visiting a website, right?

Part of the 3239 word, 27 point,Terms and Conditions:

News-Medical hereby discloses that a commission or listing fee may be payable by Experts to News-Medical for any fees received by them as a result of an introduction of a client through the Website.  

Unsurprisingly, the site's underlying purpose is to sell stuff.

Besides industry news, news-medical, based in Australia, cheaply repackages health information from several sources, including a heavy reliance on Wikipedia under the Creative Commons Attribution-ShareAlike License.

Below is my summary of a few highlights of OCD’s Celia Tombalakian's interview with news-medical.net in question and answer format, with my comments, aka musings, in italics. Readers are directed to the full interview for exactly what she said. 

The report is selective and my approach is facetious in places. But is it off the mark? You be the judge.

QUESTION: How is the blood banking industry currently being transformed?

CT's ANSWER

CT: Current focus is to improve transfusion safety and efficiency through technology solutions.  

Ah, safety and efficiency, with safety mentioned first. Who can argue?

CT: Over past 20 yrs, the number of highly skilled technologists and scientists entering the global TM workforce has shrunk. 

CT: Therefore, automation is becoming a standard part of blood bank laboratories because it eliminates many of the labor-intensive, time-consuming manual testing that requires specialized skills and significant experience to master.  

Really? Her response implies that automation arose because of staff shortages, which misleads in a chicken and egg sort of way.  

Why has the highly skilled technical and scientific TM workforce shrunk? Many reasons around the globe, inc. poor compensation for education involved (mainly USA), decreased health care funding, leading to regionalization and centralized testing, all facilitated by automation.  Automated instruments continue to be marketed on their ability to decrease absolute numbers of highly skilled staff.

CT: Ultimately, automation can increase a lab’s capacity and help it operate more efficiently, even with a smaller staff. 

A case can be made for how instruments are more reliable than humans, at least for some things. But notice there's no more mention of safety, only efficiency.

QUESTION. Tell us about the new Bloodbanker App and its benefits over traditional blood banking tools.

CT's ANSWER

CT: ORTHO's Pocket Blood Banker app is an educational reference tool that combines genotyping and antibody indexing. Users can quickly determine genotypes based on results with Rh antisera via the Genotype Calculator and learn more about antibodies with the Antibody Index.

CT: Prior to the app, blood bankers used reference tools such as cardboard slide rules. 

You gotta be kidding. Cardboard slide rules? Maybe that's what Ortho supplied customers back in the Jurassic age, but for decades I and many others taught MLS students how to determine Rh genotypes using their ... wait for it ... inbuilt computers, aka brains.

Reminds me of this exquisite Danish humour on computers: Medieval helpdesk

CT: Drawing from a deep understanding of the importance of and need for innovation in blood banking, OCD identified the need for more advanced tools and developed this new technology. The app reinforces our commitment to providing innovative solutions to our customers. 

OMG, classic marketing and branding. We're wise, we're innovative, we're dedicated to helping clients. Please bring us cute babies to kiss. 

QUESTION: Could you introduce Ortho ON DEMAND and how it fits with OCDs overall focus?

CT's ANSWER

CT: ON DEMAND is an innovative virtual engagement platform that enables blood bankers to learn from and connect with experts on topics central to achieving science-driven safety and efficiency in the blood bank. 

Attempt to reinforce Ortho's brand as innovative, Also love 'virtual engagement platform' and 'science driven.' Buzzwords convey modernity and objectivity, respectively. And note re-introduction of the safety and efficiency double whammy.

CT: With OCD’s strong TM history, we understand the importance of supporting industry through education and awareness. 

We're the pros, we understand. Trust us.

CT: Because many of today’s blood bankers work longer hours with fewer financial resources, many laboratories have had to cut costs that previously supported career growth opportunities. Through our new platforms, we hope to help prepare blood bankers to address growing demands for TM expertise. 

Excuse me? Labs have had to cut CE and CPD funding because staff work longer hours with less money? Does not compute. Pure bafflegab.

As for helping a growing demand for expertise, is there a growing demand for expertise? If so, it's to address what automation created in the first place, namely a diminished demand for technical and scientific expertise with fewer positions for TM specialists.

Frankly, automation and apps both contribute to and help alleviate a 'dumbing down' of the profession. I acknowledge that 'dumbing down' is a harsh catch phrase for staffing with less qualified personnel, not that such staff are dumb. I use the term to emphasize that apps do not contribute to developing expertise, but rather exist to alleviate lack of it.

QUESTION. What impact do you think these initiatives will have on blood bankers?

CT's ANSWER

CT: Many of today’s blood bankers struggle to do more with less, working longer hours with fewer financial resources. Concurrently, instrumentation is more complex and the number of transfusions is increasing globally. 

Meaningless bafflegab. Yes, cost constraints force blood bankers to do more with less.  

But instrumentation is more complex? More complex than what? Earlier instruments? Manual testing? Do sales reps' spiels include these words?  "Hey, our instrumentation is more complex. You need better trained dudes to operate it."   

Also, in an age of blood conservation and a kazillion studies on real and unproven potential transfusion dangers, what evidence exists that transfusion numbers have increased? Does not compute.

CT: With reduced resources, many labs cut travel costs to learning events that could better prepare staff to address growing demands for TM expertise. Ortho ON DEMAND addresses this challenge by offering TM professionals free access to education according to their own schedules.

Offering free online education has merit. But it's not exactly true that today's over-worked TM professionals are clamouring to access education on their own schedules. Employers allot no time during work hours. Staff who are under-paid and feel under-appreciated are increasingly less motivated to take time away from families to further their careers.

QUESTION: How do you think the future of blood banks will develop?

CT's ANSWER

CT: While technology has made many routine BB tasks faster and easier, the demand for blood continues to rise and the pace of processing blood continues to accelerate.  

Demand for RBC transfusions (type that automated instruments process in transfusion service labs) is increasing? Where's the evidence? Surely all the efforts on blood management, blood conservation, and improved utilization are having an impact on RBC usage.

Pace of processing blood continues to accelerate? What does this mean? I could speculate but she doesn't explain.  

CT: Hemovigilance and ensuring efficiency is of utmost importance to blood banks in maintaining a safe and accessible blood supply while keeping pace with accelerating demand for blood processing. 

Sounds good but what has hemovigilance to do with OCD's automation and apps? And again the unexplained 'accelerated demand for blood processing.'

CT: The future of blood banks lies in technological solutions that will allow blood bankers to increase safety and efficiency in order to provide the best possible outcomes for patients. 

Motherhood statement. But where is the evidence that automated ABO and Rh group testing and automated antibody screening have improved outcomes for transfused patients? Or that apps that generate Rh genotypes and describe antibodies have made a difference? 

Surely, getting patient identification correct when drawing blood samples and correlating patient identity to crossmatched donor blood when administering blood remain THE hallmarks of safe transfusion practice, the 'right patient, right blood product, at right time' mantra. 

QUESTION: What are OCDs plans for the future? Would you like to comment further?

CT's ANSWER

OCD is the global leader in Transfusion Medicine, stemming from a 70-year history of protecting the safety of the worlds blood supply. We intend to continue our leadership of the market into the future, both with our products and through our service and support of the blood banking community. 

Forgive me, but I'm jaundiced. Although I've known, liked, and respected many Ortho reps, having just read Blood Medicine (aka Blood Feud) about Ortho Biotech and Amgen's marketing of EPO products, protecting patient safety as applied to J & J or any Big Pharma company rings hollow.
Author Q & A

2. WEBSITE

Simply put, Ortho ON DEMAND offers varied worthwhile educational talks by respected TM professionals, but promotes automation. To illustrate, the first 4 talks in its Presentation section are about automation. 

I'm reminded that Ortho and its competitors such as Immucor operate on a razor-blade business model: cheap razors (instruments), with the real money made on expensive blades (reagents).

3. RESEARCH PAPER
This paper by OCD employees further shows how industry treats TM professionals like poodles, hoping to baffle brains with BS. 

• South SF, Casina TS, Li L. Exponential error reduction in pretransfusion testing with automation. Transfusion. 2012 Aug;52(8):81S-87S.

Interestingly, one of the authors, TS Casina, an OCD marketing manager, also penned these 3 articles:

Casina TS. Technologies to improve the future of blood banking. Med Lab Obs 2011 Oct;43(10):32. Excerpt:

• 'As the labor force shrinks, the rapidly evolving field of laboratory medicine is struggling to keep pace with the growing demand for blood and its components. Automation is becoming a standard part of blood bank laboratories because it can help eliminate the labor-intensive, time-consuming manual testing processes that require specialized skills and significant experience to master.'

Casina TS. What's new in transfusion services. Advance for Med Lab Professionals. Posted online 19 Sept. 2012. Excerpt:

• Transfusion of incompatible blood has the greatest potential for severe adverse events and health complications, including death. Fortunately, due to advances in transfusion medicine (TM) practices -improved blood testing, donor screening and the advent of automated systems - the blood transfused to patients is safer today than it's ever been.

Casina TS. References for "transfusion medicine reactions. Advance for Administrators of the Laboratory 2012 Oct;21(10):20. This paper is a reworked version of the one above. Excerpt: 

• A study conducted by Ortho Clinical Diagnostics provides quantitative evidence of how automation could transform pretransfusion testing processes by dramatically reducing error potentials and thereby improve the safety of blood transfusion.  Evaluating the common testing methods above and leveraging failure modes and effects analysis (FMEA) to compare error potentials, the group concluded that automation significantly reduces defect opportunities in pretransfusion testing and could dramatically improve blood transfusion safety.

Can you see how marketing managers use a full court press and recycled material (with the help of willing publishers desperate for articles) to get their message out to industry's poodles, namely us?

Abstract Highlights (Transfusion paper)

BACKGROUND: Human error associated with manual pretransfusion testing is a cause of transfusion-related mortality and morbidity and most human errors can be eliminated by automated systems. 

STUDY DESIGN AND METHODS: Study’s goal was to compare error potentials of commonly used manual (e.g., tiles and tubes) vs automated (e.g., ID-GelStation and AutoVue Innova) group and screen (G and S) methods. G and S processes in 7 TS labs (4 with manual and 3 with automated methods) were analyzed to evaluate error potentials of each method.

Tiles?  Really? Well, they could be large welled plates. But who uses these in routine manual pretransfusion testing?  

RESULTS: Manual methods contained more process steps ranging from 22 to 39; automated methods contained 6 to 8 steps.  

Roughly 4-5 times more steps for manual methods. Authors then use ‘risk priority numbers’ (RPN)  - trust me, you don’t want to go there -  to show manual method RPNs ranged from 5304 to 10,976 vs 129 and 436 for automated methods, conveniently making manual tests away more than 4-5 times as risky as automation.

What the hey! Let's go there. A team (needed to reduce subjectivity) of OCD researchers and staff at 7 TS labs determined how many defects were likely at each process step (defect opportunities) and decided where failures could occur, the likelihood that the failure would be identified, how frequently the failures might occur, and what the effects of those failures (severity) were. The result was a 10 point scale. An example: 

Process Step 16 (tile or plate required tapping and rocking before reading reactions) had 18 defect opportunities. 18 represents 6 wells in the tile or plate in which it was possible to undertap reactants (6 defect opps), forget to tap the plate (6 defect opps), or overtap and splash reactants among wells (6 defect opps) for a total defect opportunity of 18 at that step (6 + 6 + 6 + = 18). The severity was rated 7 out of 10.

Wow! Talk about creative number crunching to get the results you want. The mind boggles....

CONCLUSION: This study provided quantitative evidence on how automation could transform pretransfusion testing processes by dramatically reducing error potentials and thus would improve the safety of blood transfusion.

Oh sure. Is I or is I not your poodle?

MORE MUSINGS
This study’s logical fallacy posits (love that word!) that most, or even many, serious transfusion errors result from manual testing of ABO and Rh groups and manual antibody screening. It's true that manual testing has potential to create more errors than automated testing.

The best evidence of where TM errors occur comes from the UK’s annual SHOT Reports. For example, consider 

• 2011 SHOT Report

I’ll not bore you with too many specifics  - you can read for yourself - but believe me, it’s NOT all about lab staff making technical errors when manually testing. 

'Adverse reactions caused by errors' lists these causes of cumulative cases reviewed 1996-2011 (n=9925):

• Anti-D errors 
• Inappropriate & unnecessary
• Handling & storage errors
• Incorrect blood component transfused (n>3000)

To quote SHOT: Key lesson from 2011 is an emphasis again on the importance of the essential steps of the transfusion process:

• Taking the blood sample from the correct patient 
• Correct laboratory procedures
• Issuing of the correct component
• Identification of the right patient at the bedside at the time of transfusion
• It is clear from the SHOT 2011 data that identification of the correct patient remains a key issue and that this must become a core clinical skill.

BOTTOM LINE
So, what's it all about? Yes, automation can increase efficiency and increase safety by reducing human error. But is automation the TM saviour that industry reps and some TM professionals make it out to be? 

When you examine the arguments of proponents, such as OCD's Celia Tombalakian or the research of OCD employees, their arguments do not stand up to scrutiny. They continually overstate how automated testing can improve safety and propose it as magic it is not. 

Companies have a vested interest in promoting automated testing since the business model of cheap razor (instrument) and expensive blades (reagents) is what makes their industry viable. 

Their multi-media advertisements are relentlessly promoted to TM professionals using flawed arguments that show they think they own us and we are their poodles. 

FOR FUN

Industry's seeming hold on so many TM professionals brings to mind:

• You Don't Own Me (1964 ditty by Lesley Gore; this version in Australia, 1989)

• You Don't Own Me (Same song re-worked for 2012 USA election - thoroughly partisan. ALERT: Depending on your politics, you may be offended.)

• You Don't Own Me (Diane Keaton, Bette Midler, Goldie Hawn in 1996 movie The First Wives Club)

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Snip, snip, the party's over? (Musings on the seductive rise of DNA typing of blood groups)

Updated: 28 Jan. 2017 (Fixed broken links)

December's blog's title comes from

• A song by Willie Nelson: The party's over
• Single-nucleotide polymorphism or SNP (pronounced snip), the basis of most blood group DNA typing. Simply put, a SNP is a DNA sequence variation that occurs when a single nucleotide in the genome differs between members of a species or paired chromosomes in an individual.

The use of seductive is tongue in cheek. Not sure if I mean 'harmful but enticing'. Perhaps insidious would be apter, i.e., 'developing so gradually as to be well established before becoming apparent'?

The blog discusses

• Increasingly cozy relationship between TM professionals and the biotechnology industry;
• Molecular typing of blood groups and its uses;
• What DNA typing potentially means for the TM laboratory's work force;
• A futuristic farce on where all this might lead.

BLOG'S ORIGIN

The idea for this blog came from these sources:

1. Announcement in the AABB Weekly Report (17 Dec. 2010) of a new section in Transfusion devoted to blood group genomics with Connie Westhoff, currently director of genomics and immunohematology at the New York Blood Center, as the section's associate editor.
2. DNA typing resonated because a recent blog (Aug. 2010) discussed Immucor' s investment in DNA typing, specifically its purchase of Bioarray Solutions in Aug. 2008: Goldfinger's filings, a customer's toolkit (Musings on business intelligence) and Immucor's belief that "molecular immunohematology will revolutionize blood bank operations."
3. By chance, in researching a case study, I had just read two articles on molecular typing, one co-authored by Westhoff:

Westhoff CM, Sloan SR. Molecular genotyping in transfusion medicine. Clin Chem 2008;54(12): 1948-50.

Reid ME. Transfusion in the age of molecular diagnostics. Hematology 2009.

FYI: Marion Reid, a legend at the New York Blood Center and recipient of the 2006 International Woman in Transfusion Award.

COZY ARRANGEMENTS?
Interestingly, the Westhoff and Reid papers above list author involvement with Bioarray Solutions (and its earlier name, Bioarray), a company whose products DNA type red cell and HLA antigens.

Westhoff and Sloan paper's disclosure of potential conflicts of interests:Consultant or Advisory Role: C.M. Westhoff, BioArray, Ltd. and Immucor Inc. S.R. Sloan, Bioarray Solutions.

Reid paper's conflict-of-interest disclosure: The author receives research funding and royalties from patents from BioArray Solutions.

As evidenced by these examples, world class TM professionals often advise biotechnology companies and Bioarray Solutions has its share of respected advisors. Besides the three already mentioned, I came across others. It's accepted that industry needs input from professionals and the practice is common.

Of note, industry financing involving direct and indirect payment (consulting, food, travel, product samples, you name it) is estimated as high as $29 billion/year.

SO WHAT?
Questions to ponder:

• Could consulting for a biotech firm, presumably for a fee, influence a person's perspective towards the technology in general?
• How about earning royalties for a patent used by the company?
• Could association with a company, current or past, influence a person in a role as editor of a journal section specifically dealing with research and developments in the company's field?

What happens when respected, leading experts, individuals who are the targetted clients of a particulate technology, also advise the companies as consultants and later serve as gate keepers of peer review for what is often company-sponsored research?

My gut tells me that something could happen, despite the obvious integrity of those involved. Arrangements, many of which are not transparent, seem too cosy to generate confidence in the system.

Can anything be done? Perhaps not. 

DNA TYPING - TM USES
To quote from Immucor's 2010 SEC Form 10-K report in discussing Bioarray Solution's DNA technology:

"In many countries, blood pre-transfusion testing is limited to the prevention of transfusion reactions and not for the prevention of alloimmunization, which occurs when antigens foreign to the patient are inadvertently introduced into the patient’s blood system through transfusions. If alloimmunization occurs, the patient develops new antibodies in response to the foreign antigens, thereby complicating future transfusions.

By using multiplex, cost-effective molecular testing, our molecular technology allows testing to prevent alloimmunization for better patient care."

Not unsurprisingly Immucor focuses on preventing alloimmunization, as this use would considerably expand profits. As I noted in the earlier blog: "In a consumer society, if a real need does not exist, companies try to create one."

So what are the legitimate uses of molecular typing to determine blood groups?

Scenarios where DNA typing could prove useful include these scenarios (see Further Reading for more details of each scenario):

1. Recently transfused patients with unexpected antibodies who have two red cell populations.

2. Patients with a positive direct antiglobulin test where available typing antisera reacts only by the indirect antiglobulin test.

3. Fathers of infants carried by Rh negative woman with anti-D where the father is Rh positive.

DNA typing the father for the RhD gene can determine homo- or heterozygosity for D and indicate if the fetus is definitely D+ and should be monitored.

If being D-negative is possible, the fetus should be Rh typed using fetal DNA from cells obtained by amniocentesis or by testing cell-free, fetal-derived DNA in maternal plasma.

If the fetus is Rh negative, mother and fetus do not need to be monitored.

4. Pregnant women who appear to be weak D, in order to differentiate between weak D and partial D, since usually only the latter can make anti-D. Potentially, Rh immune globulin could be given only to females with a D variant who are partial D.

5. Extended phenotype matching of donor blood for patients with sickle cell disease.

The above scenarios are not exactly pressing. Many situations have work-arounds or present limited safety risks to patients. Granted they offer useful adjuncts to serologic testing.

As to the nuts and bolts of pretransfusion compatibility testing, routine ABO and Rh typing do not warrant molecular methods, nor does preventing alloimmunization in general as Immucor would have its investors believe.

WORK FORCE IMPLICATIONS
Although molecular methods for typing red cell antigens are available in some locations, today the technology is mainly used by reference laboratories to supplement traditional serologic typing methods done 'in the trenches'.

Despite good progress, significant practical and scientific limitations remain and the issues are complex, as discussed in the papers in Further Reading. Seltsama and Doescher cover the scientific issues extensively. The 'high-throughput platforms' mentioned by adherents are not quite ready for prime time live in your neighbourhood blood centre and transfusion service.

Thus, work force effects will not be snip-snip, where SNIP is defined as

• To cut, clip, or separate with short, quick strokes

Rather the SNP cut will be long and slow before staff hemorrhaging begins. But begin it will.

All TM laboratory professionals know that serology is in its last gasps. This is shown by the paucity of immunohematology papers in journals such as Transfusion. For example, December's issue has two and neither deals with red cells.

Rest assured that once 'high-throughput platforms' become widely available for molecular typing, regardless of whether sound scientific rationales exist, antigen phenotyping of all kinds will be taken over by molecular methods. It's simply too seductive, especially with so many TM leaders on side with the program.

As with automation, vendors will justify initial costs or high ongoing maintenance and supply charges (if a 'razor and blade' business model is chosen) with the promise of "reduced headcounts"  -  eliminating jobs for people in the community in favour of sending money to commercial enterprises elsewhere, where corporate profits are the main concern.

'SUGAR PLUM FAIRYLAND'
Seeing as it's the festive season, let's peek into a futuristic world populated by sugar plum fairies. I've mined some stereotypes (hope they bring a chuckle) and all is written with warm goodwill.

Here's the premise. What if companies pushing automation, other high throughput instruments, and information systems to support them have their way and almost every transfusion service laboratory job is eliminated?

In such a fairyland:

DNA typing platforms will match patients with donors for all major blood group antigens and pretransfusion serologic tests will become redundant.

Labs will be staffed by inexpensive 'multi-skilled workers' with no formal qualifications, all supervised by technical specialists (perhaps one per shift) now in a 'leadership role better aligned with their skills'.

Lab technologists / scientists will be free to take a buyout, a generous offer of $100 per year worked. They will, however, be forced to hawk their collection of syringes and tourniquets on street corners to finance a nursing education, which they can now consider since nurses no longer have much patient contact.

Since gowns became de rigeur for personal protection in the lab, they will sport white lab coats and happily be mistaken for physicians who have long claimed the lab coat as their uniform of record despite most never having set foot in a lab (too dark and dingy down in those basements). 

On the clinical side, other technology (bar code scanners, RFID, and the like) will ensure positive patient and donor unit identification. Smiling robots will administer blood transfusions, leaving nurses free to rant about newbie residents and those nitpicking idiots in the lab, have wild sex in the closets, and fantasize about Nurse Jackie one day killing Dr. House.

Yet more technology in the form of biosensors implanted in patients will decide when blood transfusion is warranted using programmed best practice guidelines, determine which components are needed, measure their effectiveness post-transfusion, and communicate all via wifi to a central information system nicknamed Big Bro (BB for short).

TS medical directors will sit in their offices playing on iPads with100s of fun apps all tailored to what Gregory House would be like as a hematologist versus a hematopathologist.

• On breaks, the wunderkind millennials will tweet each other about how to pay off student loans before retiring.
• About-to-retire boomers will obsess about stock portfolios.
• Late Generation Xers will text about how, if they hear once more how great the Beatles and 1960s were, they will throttle their parents.

SMALL MERCIES
In the absence of sugar plum fairies, when reduced serologic antigen phenotyping eventually occurs, the serologic mainstays will remain as they are now, antibody detection and identification. Thank goodness for the immune response. The party's not quite over...."These are still the days, my friends".

• Pour mes amis français / amies françaises, Le temps des fleurs.

Have a well deserved, fun-filled and relaxing holiday season with friends and family. And may the farce be with you....

FURTHER READING

Reid ME. The Rh antigen D: a review for clinicians. Blood Bulletin 2008 Apr; 10(1).

Reid ME. Transfusion in the age of molecular diagnostics. Hematology 2009.

Seltsama A, Doescherb A. Sequence-based typing of human blood groups. Transfus Med Hemother. 2009; 36(3): 204–212. Published online 2009 May 14.

Westhoff CM, Sloan SR. Molecular genotyping in transfusion medicine. Clin Chem 2008;54(12): 1948.

As always the views are mine alone. Comments are most welcome BUT, due to excessive spam, please e-mail me personally or use the address in the newsletter notice.