Lab Soft News

Glioblastomas Generate Their Own "Neoplastic" Vascular Supply

A recent article about the cell biology of glioblastomas, a very aggressive type of brain tumor, caught my attention (see: Why brain tumors hard to treat). It's a little outside the usual scope of this blog but still fascinating to me. Below is an excerpt from it:

New findings may help explain why glioblastomas, one of the most aggressive forms of brain cancer, are often so difficult to treat -- they can feed themselves, by differentiating into the intricate network of blood vessels that nourish the tumor, according to two [recently published] studies...."The general idea is that the vasculature is created by the normal tissue," said [a] cell biologist ....But these papers show that "the tumor itself is actually making its own blood vessels. It's a very different way to look at them." Glioblastomas are noted for their unusual vasculature, characterized by large, highly proliferating cells and abnormal structures. Until now, however, these vessels were thought to be derived from pre-existing brain capillaries, but no one had ever gone in a taken a close look, said [a] neurosurgeon and neuroscientist ....So she and her colleagues did just that. They looked for mutations known to exist in the tumor cells, including large amplifications and chromosome abnormalities, in the cells of the vasculature to see if they contained a similar genetic signature. Sure enough, a significant proportion of the endothelial cells carried the tumor's mutations, suggesting they originated from the tumor cells....The findings may explain why a common drug used to inhibit angiogenesis in cancer patients may not be very effective....The applications may be more widespread than just glioblastomas.... "All tumors have blood vessels," she said. "I'm hoping that this will invite researchers to look in other cancers to see if other cancers can use this pathway to derive their own blood vessels."

I don't have much to add to this item. Gioblastomas appear to be generating their own blood supply rather than depending on the adjacent normal vessels to provide nutrition. According to two new research studies, the endothelium lining the capillaries intimately associated with the tumor showed some of the same chromosomal abnormalities as the malignant tumor cells themselves. From the perspective of a malignant tumor, this makes perfect sense. Why depend on the adjacent normal tissue for nutrition? The normal cells may have other priorities or may not respond to the tumor cells signaling to increase their vascular supply. It's like people carrying a jerrycan of gasoline in the back of their cars to ensure an adequate supply of fuel.

A Fresh Look at Epic from a Financial and Strategic Perspective

The financial health and strategic goals of Epic are of great interest to those large healthcare systems that are totally dependent on the company for their EMR software (see: How to Avoid Software Vendor Lock-in and Account Control). Mr. HIStalk alerted me in a recent blog note to coverage of the company in a Milwaukee newspaper (see: Monday Morning Update 10/18/10). Here's his take on the company:

The Milwaukee newspaper profiles  Epic with some interesting facts, with the most interesting one being confirmation of our June report that Aurora is dumping its $150 million Cerner system for Epic, which will cost them an additional $100 million. A quarter billion dollars seems like a lot for an EMR considering that Aurora showed a $50 million loss two years ago and a $116 million loss last year....That article about Epic values the company at $2.6 billion, or just 3.3 times revenues. That seems about right given that Cerner’s market cap is just over 4x sales and is better diversified, although Cerner is probably less profitable for the same reason (see: Why Does Epic Keep Hammering Cerner? Mr. HIStalk's Opinion.).

Below is an excerpt from the Milwaukee article (see: Epic Systems rides wave of records upgrades):

"Right now, Epic is winning three to four times more [hospital contracts] than anyone else," said Kent Gale, chairman of KLAS Enterprises LLC, a research firm known in the industry for its customer surveys....Epic is projected to end the year with roughly $780 million in revenue. That's up from $650 million last year and $47 million in 2000. Its workforce has grown from 396 people in 2000 to about 4,000 today. It has added 500 people this year alone. All but a few dozen of them work in Verona, and its Wisconsin payroll this year will top $300 million. Started in 1979 with an initial investment of $70,000, privately held Epic now has an estimated market value of $2.6 billion....Epic's market is large health care systems and hospitals. It's particularly strong in academic medical centers....As recently as a few years ago, the conventional view was that nearly all of the market for large health systems had been claimed and that no one would want to go through the ordeal of "ripping and replacing" their existing systems.That hasn't been the case. One of Epic's strengths is the company has grown organically and patiently, steadily adding new features and applications to its software. That has enabled it to offer customers an integrated system that links hospitals, clinics and home health care as well as handles billing and other tasks. In contrast, many of its competitors have grown partly through acquisitions, stitching different features or applications into their systems over the years....Epic also has a strong following among doctors based in clinics. And they can have considerable influence when a health care system is weighing whether to move to one system for both its hospitals and clinics."The docs have the power," said [a] financial] analyst ....Epic's system isn't for everyone. Epic doesn't sell its software to small hospitals or to independent physician practices. And its system is more complex and costly. Making full use of all its features requires more training, Gale said. And some of its specialized products, such as those for oncology and radiology, still need work.

A year ago, I would have laughed at the notion that hospital physicians had any power whatsoever regarding the choice of an EMR vis-a-vis the CEO and CIO. I now agree with the financial analyst quoted above that the tables have turned to some degree. Hospital executives are anxious to put a user-friendly EMR tool into the hands of their physicians, particularly the hospitalists and house officers who are hospital employees. I also agree that many physicians favor the Epic EMR over rival systems, some of which are clunky and not very functional.

With regard to physician influence over the deployment and use of hospital EMRs, however, we are fast approaching an interesting turning point. Most physicians are extremely enthusiastic about iPads (see: iPad health care use by doctors, a comprehensive infographic). They are demanding that these tablet devices, or emerging equivalent models, be interfaced with the hospital EMR for their use as input-output devices. I hold the opinion that neither Epic nor hospital executives will ever allow iPads into hospitals for technical, political, and economic reasons. For Apple, the business model is all about control and vertical integration. This would be an anathema to both Epic and hospital execs. However, a tech blogger recently had an interesting insight into this issue (see: Apple iPad EMR):

[W]ill the iPad be a game changer for EMR. My prediction is that we really won’t see many iPad’s in healthcare much at all. Sure, there will be one here or there, but it won’t be widespread and we won’t see an “iPad EMR” that was designed to leverage the interface and technology of the iPad....Well, I don’t see the iPad EMR coming to fruition I do see the input technology that’s in the iPad and that will come out of the iPad having an effect on future input interfaces. Apple’s making a huge bet on touch interfaces with the iPad. the adpoption of touch interfaces and the technology that comes out of it is likely to have a huge influence on future EMR interfaces. One of the biggest complaints doctors have about the various EMR systems is the challenge of inputting the data. Don’t be surprised if the future EMR input methods are heavily influenced by the introduction of the iPad and the technologies that develop around it.

Will Large Health Systems Embrace Preventive Medicine and Wellness?

In response to a recently posted blog note (see: Risk for Consumers as Healthcare Systems Rapidly Expand), Dr. Doug Mitchell submitted the following comment:

Data suggest the "common wisdom" that preventive care saves tons of money is wrong. If one assumes the consolidation of systems is unstoppable, how might the above study be good news? The feds could more easily -- and with less push-back --heavily incentivize preventive care from these systems. Why? Fewer entities are easier to monitor. And if the study is right, the systems could make as much $$$ preventing disease as treating it. Costs being equal, is it better for a woman to die at age 80 because years earlier she was (a) repeatedly stented, or (b) put on statins? Of course, this scenario wouldn't decrease total expenses (the 800 lb problem). But might at least *value per healthcare dollar* be increased? Or am I in an overly optimistic mood today?

The question under discussion is a simple one. Will health systems invest some of their capital and expertise in the development of wellness and preventive medicine programs? This would seem to be logical direction to many observers including myself. The federal government is ratcheting down payments for various types of services including surgery, chemotherapy (see: The Oncology Concession Under Attack by Health Insurance Companies), and medical imaging (see: Medicare Imaging Cuts Restrict Access to Care and Discourage New Technologies Which Would Benefit Patients). Doug also suggests above that the development of preventive medicine could be accelerated if the feds were to heavily "incentivise" such care.

I personally think that the answer to this question is no for the majority of health systems in the U.S. with the rare exception of some like the Cleveland Clinic that have publicly declared, and acted as if, they are in the wellness business (see: Cleveland Clinic Wellness Institute). You may disagree but, off the top of my head, here are the reasons underlying my opinion:

• Most physicians and hospital executives see themselves as treating disease rather than preventing it; they do not view wellness and preventive medicine as a logical corollary and flip-side of the treatment of disease. In previous notes, I have tried to demonstrate the seamless continuum between wellness, predisease, and disease (see: Wellness, Preventive Medicine, and the Classic Disease Model; Predisposition to Disease and Pre-Disease on the Health Continuum).
• Hospital executives have grown accustomed to the high profit margins associated with surgery, outpatient diagnostic procedures like endoscopy, and labs/radiology and will continue to "ride this horse" as long as they can balance their budgets by doing so. In this regard, they are similar to most executives in other industries.
• Most hospital executives best understand the following strategies: revenue management from various payers, new facility construction, and mergers with other systems. They will be wary of investing in a business that they don't understand (e.g., preventive/predictive health services), even with the long-range view of offsetting the decreased revenue associated with disease management.
• If all of our healthcare expenditures were calibrated in terms of value per dollar as suggested by Doug above, our world would look vastly different. Unfortunately, the vast majority of healthcare consumers only pay attention of their health when something goes wrong. Our politicians, physicians, and healthcare executive are thus responding to the perceived needs and desires of these consumers.

Medical Imaging Replaces Biopsy in the Diagnosis of Hepatocellular Carcinoma

I believe that radiologists will soon be rendering many more definitive diagnoses than "impressions" in their reports due to improvements in imaging technology. This will place them increasingly in competition with pathologists. A recent report about the diagnosis of hepatocellular carcinoma reinforced this idea in my mind and also presented other interesting facts (see: Imaging Instead of Biopsy for Most Suspected Hepatocellular Carcinomas). Below is an excerpt from the it:

Although cross-sectional imaging is recommended by several well-respected societies as the standard of care for the diagnosis of hepatocellular carcinoma (HCC), many physicians still rely on a liver biopsy for diagnosis....[A radiologist and expert on this topic recently] discussed the importance of cross-sectional imaging as the diagnostic standard. HCC is currently responsible for more than 650,000 deaths each year worldwide, and is the third most common cause of cancer-related death. "The incidence of HCC is increasing exponentially in the United States because of the increasing prevalence of risk factors such as alcohol consumption, hepatitis B and C, and obesity," he continued. In 2001, the European Association for the Study of Liver guidelines validated imaging as the preferred method of diagnosis of HCC; this recommendation was strengthened by the American Association for the Study of Liver Disease in 2005. "Still, the vast majority of oncologists do biopsies..." [he] said. Biopsies are no more sensitive or specific than imaging, he continued, and biopsy carries about a 3% risk for tumor seeding. Although this is a relatively low risk, when seeding occurs and cancer is found outside the liver, the patient is no longer eligible for transplant. In addition, a needle biopsy can miss a tumor, and pathologists are often unable to differentiate between a high-grade dysplastic nodule and a cancer, [he] continued. "Stromal invasion is hard to detect," he emphasized...."Three different imaging methods are suitable for the diagnosis of HCC: contrast-enhanced ultrasound, which is not used much in the United States because of the widespread availability of the other 2, more sophisticated, methods — computed tomography scanning and magnetic resonance imaging, which is most commonly used. Both of the latter methods are excellent at detecting cancers larger than 2 cm. "According to societal guidelines, a lesion larger than 2 cm with hypervascularity and washout on imaging is diagnostic for HCC," ...."Imaging should be used instead of biopsy to diagnose HCC. There are no downsides to imaging. There is a lot of ignorance out there, and this issue needs to be brought to the attention of the medical community," [he concluded]. 

First of all, I was unaware that the incidence of HCC was increasing rapidly in the U.S. This does make sense in terms of the three underlying causes of the neoplasm -- alcohol consumption, hepatitis B and C, and obesity. Add this to the growing list of neoplastic complications of obesity (see: Rising Rate of Esophageal Cancer in the U.K.; Relationship to Obesity). Secondly, it's fascinating that imaging has been recommended by some medical associations as the standard of care for the diagnosis of HCC. This advice was confirmed in another reference I turned up (see: Surveillance and early diagnosis of hepatocellular carcinoma). Here is the key quote from it:

If the [liver] nodule found during US [ultrasound] surveillance is larger than 1 cm, it should be investigated further with contrast-enhanced dynamic radiological studies, including US, multidetector computed tomography, or magnetic resonance imaging. If the appearance is typical for HCC (i.e., the lesion shows hypervascularization in the arterial phase with washout in the portal venous or the equilibrium phase), biopsy is considered unnecessary and the lesion can be treated as HCC

I am sure that HCC differs in many ways from other malignant neoplasms. However, it's well known that complications may be associated with a biopsy of an internal organ such as the liver. The recommendation that the procedure should be avoided when possible seems sound. It would also be interesting to learn how the figure quoted above of a 3% tumor seeding rate for liver biopsies was established. Nevertheless, it's important to recognize that an important malignant lesion accounting for 650,000 deaths each year worldwide does not now require a biopsy for diagnosis.

How to Avoid Software Vendor Lock-in and Account Control

People new to the field of lab computing may be unaware of the risk of vendor lock-in and account control in their purchase of software. According to the Wikipedia, vendor lock-in, also known as proprietary lock-in or customer lock-in, makes a customer totally dependent on a single vendor for products and services and unable to use other products without substantial switching costs. A recent article discussed how to avoid such a situation (see: How to Protect Against Vendor Lock-In). Below is an excerpt from it:

It appears that Oracle CEO Larry Ellison is aggressively either buying or putting out of business potential competitors. SAP and HP look to be his latest targets on the latter path and his goal appears to be total account control, that is, a situation in which one vendor single-handedly has an enterprise’s entire account....However, Oracle isn’t the only company going after this total account control concept. And given total account control often has historically led to account abuse, I thought it would be timely to revisit the defenses you have when a vendor gets this bug and then decides to abuse it....In the 1980s, IBM took advantage of their near total account control and, largely due to a long line of strategic mistakes, began to look at their customers less like partners and more like mines of money that could be plundered....One option [that can be pursued to avoid account control] is to freeze new purchases [from a single vendor] and expand on other platforms. This reduces the account control over time and you can increasingly use the very real threat to negotiate more favorable terms when you renew your licensing agreements. Your second option is to negotiate some flexibility for things like virtualization during initial contract negotiations or during renewals. You do have to look at credible competitive alternatives, but in this market you should be able to find strong migration offerings from competing vendors and seriously bring them into the process to give you negotiating leverage. You may have to do one or two competitive migrations before any dominant vendor gets the hint. But this will pay dividends long term and balance out the negotiating process....Don’t let any one vendor control your decisions because they will invariably eventually figure your budget is their piggy bank and begin abusive pricing practices. If you can remember and execute against this one rule you don’t really have to worry about any vendor taking significant advantage of you.

The lesson to be learned here is that you should never, never should allow a single vendor to dictate contract terms or the level of service to your lab. This can easily occur when you are running Brand X "wall-to-wall" in your lab. One remedy for vendor lock-in is obviously to contract with multiple vendors for various software components. This idea is cleverly referred to above as competitive migrations. Labs with aging LISs often install middleware or lab outreach software to provide the new and necessary functionality that they are seeking. This approach requires attention to system integration but it's well worth the effort. Support for such a strategy can be obtained from the vendors themselves or with the help of software consultants. This constitutes the best-of-breed strategy that I favor.

Contrariwise, a best-of-breed strategy runs counter to the "total enterprise solution" that is being pursued by many hospitals CIOs, particularly with regard to the deployment of the Epic EMR and Beaker LIS (see: Are You an Enterprise or Best-of-Breed CIO? Access to Cash May Make the Difference). As noted in this latter blog note, such a solution is being adopted primarily by hospitals with easier access to capital, which is a good thing. In the long run, they will need all the money that they can get their hands on because they are relinquishing all of their contract negotiating power.

Risk for Consumers as Healthcare Systems Rapidly Expand

At a social event in Ann Arbor two nights ago, much of the talk centered about how a regional health system had just announced the purchase of a large physician cardiology group just a few months after the purchase of an even larger private group of internists. The rationale apparently was to provide the hospital system with more expertise in ambulatory care and also because the CMS is ratcheting down reimbursement for outpatient visits.The physician groups think that their revenue will be increasingly squeezed. Here are some other similar announcements (see: Kentucky's Louisville Cardiology Group Joins Baptist Hospital East; Chicago-Area Cardiology Group Joins NorthShore University Health System).

I have previously commented about the emergence of "big medicine" which consists of big payers (government and health insurance companies) + big pharma + big healthcaare providers (large health systems) (see: Physician Private Practice Declines; the Last Barrier to Emergence of "Big Medicine"). The majority of new medical school graduates will be salaried hospitalists, working for the increasingly large health systems. As highlighted in a recent article, all of this may result in higher costs for consumers rather than cost savings as originally anticipated (see: Consumer Risks Feared as Health Law Spurs Mergers). Below is an excerpt from it:

When Congress passed the health care law, it envisioned doctors and hospitals joining forces, coordinating care and holding down costs, with the prospect of earning government bonuses for controlling costs. Now, eight months into the new law there is a growing frenzy of mergers involving hospitals, clinics and doctor groups eager to share costs and savings, and cash in on the incentives. They, in turn, have deployed a small army of lawyers and lobbyists trying to persuade the Obama administration to relax or waive a body of older laws intended to thwart health care monopolies, and to protect against shoddy care and fraudulent billing of patients or Medicare. Consumer advocates fear that the health care law could worsen some of the very problems it was meant to solve — by reducing competition, driving up costs and creating incentives for doctors and hospitals to stint on care, in order to retain their cost-saving bonuses....Those agencies are writing regulations to govern the new entities, known as accountable care organizations. They face a delicate task: balancing the potential benefits of clinical cooperation with the need to enforce fraud, abuse and antitrust laws....Congress’s purpose was to foster cooperation in a health care system that is notoriously fragmented. The hope was that the new law would push doctors, hospitals and other health care providers to come together and jointly take responsibility for the cost and quality of care of patients, especially Medicare beneficiaries....“In some markets, [said an expert in the field], “the dominant hospital is like the sun at the center of the solar system. It owns physician groups, surgery centers, labs and pharmacies. Accountable care organizations (see: Hospital Executives Search for the Formula for an Accountable Care Organization) bring more planets into the system and strengthen the bonds between them, making the whole entity more powerful, with a commensurate ability to raise prices.”

This consolidation of healthcare systems will provide them with the opportunity and power to negotiate on a more equal basis with health insurance companies (see: Health Systems Use Their Regional Dominance to Muscle Insurance Companies; Comparing the Details of Hospital Charges in the State of Oregon). In reality, the insurance companies and the health systems will be sitting around the table and cosily agreeing about how to divvy up the ever-increasing pot of money being allocated to healthcare (see: As Hospital System Expands, Patient Advocates Worry). There will be no way to stop this juggernaut unless and until helathcare consumers, their employers, and the federal government yell enough for the last time. The way things are going, healthcare reform will do nothing but increase the cost of healthcare delivery.

New Melanoma Identification Device Narrowly Apporoved by FDA Panel

MelaFind, a device designed for use by dermatologists for in-vivo detection of suspicious pigmented skin lesions, has been narrowly approved by an FDA advisory panel. Here is an excerpt from the article (see: Panel Splits over Skin Cancer Detection Device):

An FDA advisory panel has voted 8-7, with one member abstaining, to recommend approval for an experimental skin cancer detection system called MelaFind. A vote so close generally is not considered an endorsement in the eyes of FDA officials, who have the final say in whether to approve the device. The FDA does not have to follow the advice of its advisory committees, but it often does. Some panelists on the [committee] were concerned that relying on a device to detect melanoma could lead to unnecessary biopsies, or worse: missed skin cancers. Those who voted against the device also were concerned that non-dermatologist physicians might start using it. "I have a problem with this," said panelist Lynn Drake, MD, a dermatologist at Massachusetts General Hospital and a lecturer at Harvard, who voted against approval. "This disease kills people. I think we need to be very careful about approving something that might replace a human's judgment." But other panelists felt that even though the device proved only slightly superior at detecting melanoma in suspicious lesions than a physician alone, having another tool to aid in skin cancer detection would ultimately benefit patients....The noninvasive device uses a dermascope with near-infrared light to image the skin through a thin layer of alcohol or oil while a digital camera captures images of the lesion. A computer connected to the dermascope displays the image on a screen in the physician's office. Software sorts out various patterns and analyzes lesion color, shape, and consistency to assign a risk that a lesion is a melanoma. MELA Sciences, the device's manufacturer, says MelaFind can visualize lesion structures under the skin.

This news item interested me for a few reasons. First of all, MetaFind is an example of in-vivo imaging technology that, at some time in the future, may replace the pathologist and histopathology in the diagnosis of various types of lesions. Other examples of such technology include molecular imaging (see: The Role of Molecular Imaging Versus Histopathology in Diagnosis) and in-vivo endoscopic imaging. Neither of these two technologies will replace the pathologist soon but it's not hard to see a trend here.

Two of the objections to the product by the panel members, quoted in the article, also caught my attention. One is the "guild defense" argument cited by a dermatologist that non-dermatologists might start using the device and thus take away work from specialists. In my opinion, this can't happen fast enough. I believe that much of the initial triage of patients during office visits should be managed by specially trained nurses. It would be an advantage for all of us if initial skin-checks could be accomplished by such nurses using a product like MelaFind. A dermatologist can be brought into the room, when necessary, at the end of the visit to confirm the clinical findings. This would be a very efficient way to address the current epidemic of melanomas.

Secondly, I was struck by the objection of one of the panel members that a downside of the device was that technology will "replace human judgement." In my opinion, only poorly-designed technology poses such a risk. Well-designed technology should always improve human performance but will provide an option to override the technology if and when human judgement is superior. This is the case when using computer algorithms to quantify tissue biomarkers in digital pathology. However and in such instances, the human operator needs to have a strong rationale for the override. After all, human expertise is used to develop the computer algorithms and the intelligence of the current operator may be superior to that which was used to develop the algorithms (see: In-Vitro Biomarkers vs. In-Situ Biomarkers). Moreover, the algorithms may also not be working properly or inadequately designed.

HIMSS Virtual Conference: Qualifying for a Reduced Fee

HIMSS seems to be up to one of its revenue-generating, marketing, and sleight-of-hand tricks according to a report by Inga who blogs with Mr. HIStalk (see: News 10/29/10). Here's her account about registration for one of its virtual conferences:

HIMSS is hosting another virtual conference November 3-4. I “attended” the first one two or three years ago, mostly because I was curious about the virtual format. The conference is free for “qualified” participants and $99 for “non-qualified” HIMSS members. I can’t find anywhere on the HIMSS site that clarifies what it takes to be qualified, but I can say that when I tried to sign up for a conference a year ago, I didn’t have the secret requirements. I am mildly amused because my status must have recently changed, having received two separate invites from HIMSS this week. I should clarify that neither invite was for “Inga,” but for her counterpart in the “real” world. Since not much has changed on my end, I have to assume HIMSS is under pressure to boost attendance, probably to please its 25+ sponsors. If I have time, I’ll probably accept an invite and lurk around a bit.

To my way of thinking, if Inga can't figure out what it takes to be qualified for the virtual conference, the requirements must be obscure. Your can count on the fact that any "educational" event sponsored by HIMSS will have some twist on it to please the participating vendors. My guess is that you need to be on some vendor list to qualify for the reduced registration fee and the company will then cover the fees for its invited guests. As I have stated previously, HIMSS is a marketing and revenue-generating organization masquerading as a professional society (see: HIMSS Describes Itself as a "Trade Association" in a Press Release; A Curious Aspect of the HIMSS Registration Process; Dropping Out of HIMSS: A CEO Speaks His Mind).

Sanofi-Aventis, Covance Become R&D Partners

Covance and Charles River are major contract research organizations (CROs) to which are being outsourced an increasingly large share of drug development and research activities by the pharmaceutical companies (see: CROs Continue to Prosper; Benefits of Big Pharma Outsourcing; Too Much Management May Account for Lack of Innovation in Big Pharma Companies; Some Evidence that Big Pharma Has Lost Its Innovation Mojo). The relationship between Covance and Sanofi-Aventis is growing even deeper according to a recent announcement (see: Covance, sanofi-aventis enter definitive agreement for R&D partnership). Here is an excerpt from the article:

Covance ...today announced the signing of definitive agreements with sanofi-aventis...for Covance to become sanofi-aventis' R&D partner. Over the next ten years, Covance expects to provide drug development services to sanofi-aventis, with estimated payments ranging from approximately $1.2 billion to $2.2 billion.  Sanofi-aventis will sell their Porcheville, France and Alnwick, United Kingdom sites and facilities to Covance for approximately $25 million and Covance will maintain employment on these sites for at least the next five years. The transaction is expected to be completed before the end of the year....Under the agreements, sanofi-aventis will utilize Covance's global R&D portfolio of discovery support, toxicology, chemistry, clinical Phase I – IV, central laboratory, and market access services with annual commitments for these services increasing over the next decade. These agreements include a 10-year sole-source relationship for central laboratory services. Covance will acquire CMC (Chemistry, Manufacturing and Controls) services with the addition of the Porcheville and Alnwick sites, including preformulation, drug formulation, preclinical and early-stage clinical API (Active Pharmaceutical Ingredient) manufacturing, and radiolabeled chemistry.

The relationship between Covance and Sonofi-Aventis could not be made any clearer than what was stated in the press release. Covance is Sonofi-Aventis' R&D partner and is acquiring two of the pharmaceutical company's major research facilities. The functions being turfed to Covance, as stated in the article, seem quite broad to me: discovery support, toxicology, chemistry, clinical Phase I – IV, central laboratory, and market access services. The question remains in my mind about what key functions will remain with this global pharmaceutical giant when it seems that so much is being outsourced to its CRO partner? I could not discover any answers to this question as the result of a quick web search. Perhaps one of the readers of this blog has an answer.

Blood Doping and Entry into Clinical Trials for Chemotherapy

A number of initiatives are underway by insurance companies to limit the type of chemotherapy that is delivered to patients to "standard" protocols. This should be interpreted to mean the use of chemotherapy that has been proven to be effective (see: The Oncology Concession Under Attack by Health Insurance Companies). Appropriately, experimental drugs and combinations or drugs are best administered during clinical trials that are managed with research protocols. These always incorporate the clinical criteria for the admission of subjects to the study in order to create a homogeneous pool of subjects. Some patients (and/or their physicians) appear to be so anxious to participate in these trials that the patients are being administered blood and blood component transfusions for the purpose of meeting the clinical eligibility criteria for trials. This practice raises both ethical and patient safety concerns (see: Blood Doping Now a Problem in Cancer Trials). Below is an excerpt from the article:

Three instances in advanced cancer patients over a one year period were reported by Jeannie L. Callum, MD, and colleagues at Sunnybrook Health Sciences Center in Toronto (Callum JL, et al "Transfusion for protocol eligibility" N Engl J Med 2010; 363: 1681-1682.) "We caution against this practice, given the risks of transfusion," they wrote in a letter to the editor that appeared in the Oct. 21 issue of the New England Journal of Medicine. All three cases they reported involved patients trying to get into trials of novel chemotherapy agents. The first patient had an albumin level of 22 g/L but needed to be at 30 g/L to get into the trial and thus took a transfusion of 25% albumin. The second patient fell just under the required platelet count of 50,000 per cubic millimeter with a pretransfusion count of 48,000. The physician of a third patient ordered transfusion of a unit of red cells to raise her hemoglobin level from 8.3 g/dL to the required 9.0 g/dL for trial enrollment. These cases might have been handled otherwise, [the researchers] noted. Clinicians should try to correct the underlying laboratory value through other treatments first, such as treating anemia, they urged. Explore all possible other options, including looking for other trials at other institutions for patients who don't meet eligibility criteria, they added.

An obvious question is the motivation of the transfusing physicians in these three cases. Since the blood and platelet abnormalities were relatively mild in all three cases, one obviously suspects "blood doping", which is to say "touching up the patients" in order to qualify them for admission to the trials. Obviously and as stated in the letter, the organizers of cancer clinical trials need to be vigilant going forward about this practice. More importantly, the transfusing physicians need to accurately report the patent's transfusion history when entry is being sought into a trial.