Economically-Motivated Herb Adulteration

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As early as 2006, I used to be able to write monthly about US FDA warnings on erectile dysfunction supplements being found adulterated with prescription drugs such as sildenafil, the phosphodiesterase-5 inhibitor found in Viagra. These adulteration episodes raised the question of how many anecdotal reports of herbal products “working” had to do with them containing approved medicines.

So common was this practice that FDA created a site in 2008 that was dedicated to this problem: Hidden Risks of Erectile Dysfunction “Treatments” Sold Online. Indeed, these products were more commonly encountered from online retailers and not in health food stores. Other similar practices include bodybuilding supplement being spiked with anabolic steroids and weight loss supplements being adulterated with sibutramine (formerly Meridia), an anorectant removed from the market last year after showing increased incidence of heart attacks and stroke in patients with preexisting cardiovascular disease.

The herbal industry, led by the American Herbal Products Association (AHPA), aimed to clean up this problem and launched an initiative called, KeepSupplementsClean.org. Spurred by an FDA letter to the industry on 15 December 2010 of increased scrutiny on the adulteration problem, AHPA actually encouraged FDA to root out manufacturers who adulterated their products or failed to qualify suppliers of their raw materials.

AHPA has publicly expressed its support for FDA actions against marketers of products that masquerade as dietary supplements but contain illegal ingredients. AHPA encourages FDA to use its regulatory authority to hold accountable those who violate the law and jeopardize the public confidence, including all legal means to enforce the law.

The initiative seems to have been effective. This week, the independent testing organization ConsumerLab.com reported that testing of 11 “sexual enhancement” products revealed no adulteration with prescription drugs. On the other hand, the organization showed that, “[f]our products contained less of a key ingredient than claimed on the label, one product was contaminated with an unacceptable level of lead, and two products lacked FDA-required information on their labeling.”

Economically-Motivated Adulteration

This week also saw increased attention on another problem: herbal supplements containing less-expensive plant materials, some of which can cause liver damage. A US Department of Agriculture group has published an analytical method to detect adulteration of Scutellaria lateriflora L. (American skullcap) with two species of germander, a plant well known to contain compounds bioactivated by cytochrome P450 to reactive chemicals that damage the liver. The group of Vanderbilt University biochemist Larry Marnett showed in an elegant 2007 Chemical Research in Toxicology paper how the germander compound teucrin A is activated and identified key proteins in the liver that are chemically attacked by the reactive metabolite.

Skullcap supplements are normally taken to relieve anxiety and do indeed contain flavone compounds that bind to the benzodiazepine site on GABAA receptors like some prescription drugs. However, the herb hasn’t fared well in clinical trials for anti-anxiety activity.

Well, how’s this for increasing anxiety: In the current USDA study, 13 Scutellaria lateriflora products were tested using the new method and four were found to contain teucrin A, indicating that the products contained germander.

But this is apparently old news. In a NutraIngredients USA article that discussed the paper’s findings, American Botanical Council founder and Executive Director Mark Blumenthal called the finding, “disappointing, but by no means surprising,” noting that,

Many experts in the herb community have known about this misidentification for many years, he said. “ABC published an article by botanist Steven Foster about this problem in HerbalGram in the fall of 1985! Foster cited this problem as having been around for decades.

Indeed, one can find on the ABC website a nice monograph by Gayle Engles on the history of skullcap use and the cases of human hepatotoxicity from the 1980s.

The use of cheaper materials in drug and supplement products came to light with melamine used to artificially boost apparent protein content in pet food and infant formula products in China. In 2009, the Council for Responsible Nutrition released a statement on the problem of economically-motivated adulteration in the supplement industry. While the new Good Manufacturing Practice guidelines for the industry were intended to address this issue, the current USDA analytical paper tells us that more stringent enforcement of the rules is necessary.

Until then, be careful when taking herbs for anxiety. Because that’s exactly what you might get.

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Who’s to Blame for Drug Shortages?

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All the best effort to practice science-based medicine are for naught when the optimal treatment is unavailable. And that’s increasingly the case – even for life-threatening illnesses. Shortages of prescription drugs, including cancer drugs, seem more frequent and more significant than at any time in the past. Just recently manufacturing deficiencies at a large U.S.-based contract drug manufacturer meant that over a dozen drugs stopped being produced. This lead to extensive media coverage, speculating on the causes and implications of what seems like a growing problem. So who’s to blame?

First, some perspective. Drug shortages are not a new problem. I’m a pharmacist who has worked in almost every healthcare setting – and dealing with shortages is a time-consuming and frustrating part of the the profession. However, the perception, even among health professionals, is that this situation is worsening. Statistics back this up. U.S. sources accurately track the prevalence of drug shortages and it hit a record high in the first half of 2011, with over 180 drugs reported to be in short supply. Before you blame the dysfunctional American health care system – it’s not just there. The same issues are occurring in Canada, and the United Kingdom, an some are worldwide. Managing shortages is a problem that affects all aspects of a patient’s treatment. Consider the impact of a cancer drug that disappears suddenly from the market, which looks to the be the case with the chemotherapy drug Doxil:

  • Pharmacists struggle to ensure inventory levels are in place to meet treatment demands. Managing supplies can be a daily crisis.
  • Cancer centres and hospitals struggle to coordinate treatment plans, unsure if necessary drugs will be available. In some cases, substitutes may be necessary. So called “grey market” vendors may take advantage of the shortage, buying up dwindling stock and then reselling it, at tremendously inflated prices [PDF].
  • Insurance plans need to confirm payment of alternative treatments and elevated prices.
  • Physicians are concerned about the impact on treatment regimens and the consequences of substitutions and delays on treatment plans.
  • Cancer patients, already dealing with a cancer diagnosis, may be concerned about access to their treatments, and the possible health consequences of delays and changes. They’re at a greater risk of medication errors due to switches in drugs and doses.

The shortage is so bad with Doxil that new patients may not start therapy – the dwindling supplies are restricted only to patients already on treatment.  While not all shortages are this bad, sterile injectable drugs seem to have the biggest supply problems problem. And when generic versions don’t exist, there’s no exact substitute. So where are these shortages coming from?

Causes

Drugs can be in short supply for two main reasons. Demand can grow and outpace supply, or the supply can be reduced, and there’s an inability to meed demand. All signs point to current shortages being a consequence of supply problems.

There is no single cause to supply interruptions. One of the biggest factors is changes in the generic drug industry. (Generic drug manufacturer can produce a product after it losses patent protection). Consolidation in the industry means there are fewer companies that will produce any product. And the manufacturers may outsource their production to contract organizations, due to the technical requirements involved. (Take a look at this Health Canada advisory which notes that one plant manufactures drugs for several different companies) .

What causes manufacturing issues? Problems emerge throughout the supply chain. In many cases, it’s regulatory agencies like the Food and Drug Association that identify quality or safety issues, interrupting production. With manufacturing increasingly becoming a global endeavor, the FDA now sends inspectors to plants in China and India where all or part of the supply may originate. It may be difficult to obtain or process raw materials that meet FDA quality standards. When problems emerge, manufacturers may decide that supporting production for low-profit or low-volume products doesn’t make economic sense. Combined with industry consolidation, the result is a dwindling number of companies willing to produce a product – and no excess capacity when there are interruptions with one supplier. A survey conducted [PDF] by the American Society of Health-System Pharmacists identified that product quality issues were the most common reason for interruptions, followed by discontinuations, capacity issues and delays, and raw material issues.

Some have attributed shortages to being a consequence of generic drug reimbursement policies. That’s what Ezekiel J. Emanuel argued in a recent New York Times op-ed. He argues that (U.S.) Medicare pricing policies have made selling generic drugs unprofitable, driving companies from the market.  But given shortages are are nothing new, sometimes involuntary, and exist worldwide, there’s no persuasive evidence that directly links reimbursement rates to supply issues. Tendering and bulk purchasing of pharmaceuticals, another common approach to purchasing, have the potential to impact supply, if a manufacturer given market exclusivity is suddenly unable to meet demands. But again, there’s no direct evidence that’s been the case, either in Canada or the USA.

A drug shortages summit in 2010 [PDF] pointed to FDA regulations and barriers as significant factors that contribute to shortage. Problems included the inability to require shortage notifications from manufacturers, as well as a FDA initiative to require manufacturers to properly license previously unapproved drug products.

Analysis

While there is no shortage of policy papers, summits and calls for greater (or reduced) regulation, there’s been very little concrete action taken to actually solve the problem. And that’s because no group, agency or even country has control and influence over the entire supply chain. And more importantly, no group or regulator has the responsibility for ensuring that shortages don’t occur.

The supply chain that links the chemical synthesis to the administration to a patient is intricate, to put it mildly. This process involves companies that manufacture the active pharmaceutical ingredient (the active ingredient), to the company that packages it for administration, to the pharmaceutical company that sells and distributes the product. Regulators (one for each country) verify manufacturing standards before allowing sale. Once licensed for sale, wholesalers distribute the drug, group purchasers consolidate purchasing among hospitals or HMOs, insurers and public payers decide which drugs will be benefits, and then hospitals purchase and administer the drug.  Depending on your health system, the players may be different. But one feature is universal between health systems:There is no single organization responsible for ensuring this complicated process ensures that once started, supply isn’t interrupted.

Looking for solutions

There’s no sign that drug shortages will disappear in the future. Signs point to continued or worsening challenges, if no action is taken. Can this problem be solved?

In the USA, legislation has been proposed that would require manufacturers to notify the market six months before any supply interruption, and make other changes to improve transparency about supply interruptions. There have also been proposals that the US Centers for Disease Control should stockpile chemotherapy products, like it already does for other drugs.

But these approaches don’t affect underlying challenge: No-one “owns” the supply issue.  And there is no single cause of shortages. That’s the challenge: Building accountability for drug supply throughout this complex pathway. There are other complicated supply chains in the world – perhaps there’s something that can leveraged from other industries and transplanted into healthcare. Because we all need to stay focused on who is at the receiving end of the supply chain: The patient, wondering if they’re going to get their medicine.

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Acupuncture and Acoustic Waves

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Here is yet another study claiming to show “how acupuncture works” when in fact it does nothing of the kind. It does, however, reveal the bias of the researchers – it is, in fact, surprising that it was published in a peer-reviewed journal. Unfortunately, the mainstream media is dutifully reporting the biased claims of the researchers without any independent verification or analysis.

There are numerous fatal problems with this study. The first, like in many physiological studies that purport to be about acupuncture, is that the connection to acupuncture is tenuous. The researchers claim that they are testing the effects of an acupuncture needle – but what makes a needle an acupuncture needle? Other such studies were ultimately just seeing the effects of local tissue trauma. The fact that this trauma was induced by an “acupuncture needle” is not necessarily relevant.

This study is far worse, because it is simply using the acupuncture needle as a mechanism for inducing an unrelated physiological stimulus. This is similar to “electroacupuncture” where electrical current is applied through an acupuncture needle – what you are actually studying is the effects of electricity, not “acupuncture.” Applying electrical stimulation, or some other physiological stimulus, is the equivalent of injecting morphine through a thin needle and then claiming this demonstrates how “acupuncture works.”

This is the most significant fatal flaw of this study. What the researchers did was use an”acupuncture needle” (i.e. a needle) to apply a mechanical vibration (through a piezoelectrical device – one that converts electricity to mechanical force, or vice versa) to the tissue. They justify this procedure by likening the vibration to manual manipulation that acupuncturists will do to the needle after insertion.

However – they were vibrating the needle at up to 50 hz – 50 times per second. There own data shows that low frequencies have no physiological effect. Essentially the researchers were measuring acoustic shear waves (ASW) in the tissue in response to this vibration. This is less than shocking – vibrational waves in tissue in response to vibration. But they also measured the release of calcium by the cells. They argue that the ASW cause the local cells to release calcium which then in turn triggers the release of endorphins – and that’s how acupuncture works.

What they actually showed, if anything, is that acupuncture does not work through this mechanism. They proved the opposite of what they claim, because their own data shows that the calcium release is present at 40hz, it is barely present at 20hz, and completely absent at 10hz and 5hz. So, to be generous, unless the acupuncturist is continuously vibrating the needle at 20 times per second, the physiological mechanism they are seeing is not relevant. It’s impossible, using just your hands, to vibrate a needle at 20hz. Further – acupuncturists don’t vibrate the needle, they may twist them or move them up and down, but not at anything approaching 20hz. The authors themselves state:

In studying acupuncture, an important and frequently overlooked procedure is the manual needle manipulation performed by acupuncturists after needle insertion. The needle manipulations are typically a series of rapid bidirectional rotation or up-and-down piston movements.

The authors failed in the most basic sense to demonstrate that their physiological model is at all relevant to acupuncture; they failed to note the relevance of the frequency of the vibrations they were using or the plausibility that this relates to the “rapid” movements of the needle that acupuncturists sometimes make.

It should be further noted that in clinical studies the movement of the needle by the acupuncturist, when controlled for, does not contribute to a measured clinical effect. The effect of the needle movement is the major premise of this research, and yet it does not appear to be true.

The study also looked at the acoustic waves themselves and claim that they were more pronounced when the needle was inserted at an acupuncture point than when at a non-acupoint. I find this result frankly unbelievable. A review of the research does not support the notion that acupuncture points or meridians exist. Further, the clinical research shows that there is no difference in effect between needling acupuncture points or non-points (sham vs “true” acupuncture). About this the authors write:

Along with it is a system of tracks called meridians by the practitioners but invisible anatomically.

By “invisible anatomically” they mean – there is no evidence they exist. Meridians are the floating, invisible heatless dragons of Carl Sagan.

The fact that these researchers found results that depend on the existence of acupuncture points seriously calls into question their methods. Their results should be viewed as the equivalent of N-rays or Bem’s future cognition results – likely artifacts of sloppy research and researcher bias.

It should also be noted that this study did not even look at clinical effects from acupuncture, so they were unable to correlate any of the physiological parameters they were looking at with any putative effect. Therefore there are good reasons for thinking the effects they are seeing are not relevant to acupuncture, and the researchers provide no evidence that they are.

The flaws outlined above are enough to render this study useless as support for acupuncture, but I think it’s also worthwhile to consider the bias of the researchers. I usually don’t spend time doing this, but there are a few points worth making with respect to this study. This study comes out of Hong Kong. There is a Columbia University author, but he is a non-MD electrical engineer who provided only technical assistance, and is not a medical researcher. This is relevant because a prior review of acupuncture research published in 1998 showed that 100% of the acupuncture studies coming out of Hong Kong (and several Asian countries) were positive. This is in stark contrast to acupuncture studies from the West or overall.

The most reasonable conclusion to draw from this is that there is extreme researcher and/or publication bias in these countries. Proponents might argue that Asian researchers know how to do acupuncture properly, but that explanation is not credible, and doesn’t apply to physiological studies like the current one.

I also note that one of the lead authors, Siu Kam Lam, was convicted of stealing 3.8 million dollars in donations while in public office and served jail time for this crime. Facts like this are always difficult to deal with. Withholding this information from this article seems like an omission, as this might be relevant in putting the honesty of the researchers into context. But it can also be interpreted as poisoning the well. In any case – I see it as full disclosure, and the reader can make of it what they will.

I will also note that the authors, in their introduction, give a glowing review of acupuncture, and shamelessly cherry pick the evidence to make it seem as if there is good published support for acupuncture. The opposite is true – systematic reviews show that there is no specific effect from acupuncture. It is nothing more than a ritualized placebo.

Conclusion

There is no evidence for any of the underlying claims of acupuncture – not even the existence of acupuncture points. The clinical research shows that acupuncture does not work – in other words, that it does not matter where or even if you stick the needles. Acupuncture is a placebo treatment.

Acupuncture proponents, however, continue to study the non-specific local physiological effects of sticking needles into tissue, and often even producing a physiological stimulus through the needle that has nothing to do with how acupuncture is practiced. They then claim that “finally” they have discovered how acupuncture works – begging the question of if acupuncture works.

This current study is no exception. But interestingly, this study may be the first that actually proved that they found a mechanism by which acupuncture cannot work. The effect they found was only present when the needle was vibrated at 20hz or more – something which is not done and seems impossible for the acupuncturist to achieve.

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Are Prenatal Ultrasounds Dangerous?

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Several questionable sources are spreading alarms about the possible dangers of prenatal ultrasound exams (sonograms). An example is Christine Anderson’s article on the ExpertClick website. In the heading, it says she “Never Liked Ultrasound Technology.”

[She] has never been sold on the safety using Ultrasounds for checking on the fetuses of pregnant women, and for the last decade her fears have been confirmed with a series of studies pointing to possible brain damage to the babies from this technology.

Should We Believe Her?

Should we avoid ultrasounds because Anderson never liked them? Should we trust her judgment that her fears have been confirmed by studies? Who is she?

“Dr.” Christine Anderson is a pediatric chiropractor in Hollywood who believes a lot of things that are not supported by science or reason. Her website mission statement includes

We acknowledge the devastating effects of the vertebral subluxation on human health and therefore recognize that the spines of all children need to be checked soon after birth, so they may grow up healthy.

It also states that “drugs interfere… and weaken the mind, body, and spirit.” Anderson is a homeopath, a craniosacral practitioner, a vegan, and a yoga teacher. She advises her pregnant patients to avoid toxins by only drinking filtered water and only eating organic foods. She sells her own yoga DVD.

In her own pregnancies she refused ultrasound and other prenatal screening tests. This was her idiotic reasoning:

I trusted in my body’s innate wisdom that if the pregnancy was moving forward, then everything was going OK in my baby’s development.

Apparently on her planet if a pregnancy has not spontaneously aborted that means the baby is developing normally, and no abnormal child is ever born. And perhaps all the children are above average?

She believes in many alleged benefits of chiropractic that are not substantiated by any evidence. She says that our emotions create chemical changes in our bodies that can affect our developing babies; and that chiropractic helps to keep those feel good chemicals flowing freely. She believes that chiropractic frees up any interference to the nervous system and since the nervous system controls all the functions in the body, chiropractic manipulations allow the organs to optimally process any toxins they encounter. She believes getting regular chiropractic care reduces labor times.

Based on this, I am not impressed by her medical judgment or her understanding of biology or science, but that doesn’t necessarily mean she is wrong about ultrasound. What does she say?

Alleged Risks of Ultrasound According to Anderson

  • Ultrasound heats the tissue and researchers suspect that the waves cause small local gas pockets which vibrate and collapse called cavitation. The gas can reach up to temperatures of thousands of degrees (Celsium) [sic] leading to production of potentially toxic chemical reactions.
  • Studies done on mice have shown intestinal bleeding caused by changes in the cells. Scientists conclude that there would be similar effects in humans.
  • Ultrasound has been linked to the following abnormalities:
    • Left handedness in children who are supposed to be right-handed. Although there is nothing inherently wrong with being left handed, the change is attributed to a subtle damage to the brain. Males are more affected than female fetuses, probably because the male brain develops later.
    • Early labor, premature birth, miscarriage, low birth weight, poorer health at birth, and perinatal death.
    • Increased learning disabilities, epilepsy, delayed speech development, dyslexia

She also alleges that no studies have been done to prove the safety of these devices. This is demonstrably false.

Elsewhere, prenatal ultrasound exposure has even been accused of causing autism although a study found no association.

Risks According to Scientists

Obstetricians and radiologists who have evaluated the peer-reviewed literature have found no evidence of harm except for an apparent correlation between ultrasound exposure and left-handedness (in males only!).  Such odd-sounding correlations are usually not significant, and are mostly good for a chuckle.

Experts place little reliance on the mouse studies, since the dosages tested were higher than what humans are exposed to and since no corresponding clinical consequences have been detected in humans. Nevertheless, they acknowledge theoretical reasons for concern, and they recommend that medically unnecessary ultrasounds be avoided under the precautionary principle.

Does Routine Ultrasound Affect Outcomes?

A large study (15,530 women) published in The New England Journal of Medicine found that routine screening did not reduce perinatal morbidity and mortality.  There were no significant differences in the rate of preterm delivery, distribution of birth weight, or outcomes within the subgroups of women with multiple gestations, small-for-gestational-age infants, and post-date pregnancies. Finally, the detection of major anomalies by ultrasound examination did not alter outcomes. The authors pointed out that routinely screening more than 4 million pregnant women annually in the United States at $200 per scan would increase costs by more than $1 billion.

A Finnish study found that perinatal mortality was significantly lower in the screened than in the control group (4.6/1000 vs 9.0/1000); but this was attributed to improved early detection of major malformations which led to induced abortion. All twin pregnancies were detected before the 21st gestational week in the screening group compared with 76.3% in the control group; perinatal mortality in the small series of twins was 27.8/1000 vs 65.8/1000, respectively.

Caveats: These studies did not look for long-term consequences like learning disabilities. And there are other considerations besides morbidity and mortality. Ultrasound can reassure patients or allow them to plan ahead for multiple births or abnormal infants, and it can guide obstetric management.

Reasons for Doing Ultrasounds

Ultrasounds can detect fetal abnormalities and can help guide obstetric care by detecting problems like multiple fetuses and placenta previa. There are many legitimate reasons for doing them, especially in high-risk pregnancies or when a specific problem is suspected.

Reasons for Not Doing Routine Ultrasounds

False alarms can be raised. Apparent abnormalities may cause worry but turn out not to be significant. Placenta previa detected early in pregnancy frequently resolves before delivery.

There is no way to completely rule out the possibility of a low risk of long-term consequences. Trying to identify such consequences by even the most careful epidemiologic studies is fraught with pitfalls, since if you look for every possibility you will inevitably find a few spurious correlations. Experts agree that routine ultrasound screening is not necessary in low-risk pregnancies and that ultrasounds for nonmedical reasons should be discouraged.

Some nonmedical uses are particularly objectionable. Ultrasounds are being used in India and elsewhere to determine sex for the purpose of aborting undesired female fetuses.  Ultrasound is being commercially promoted for “keepsake” pictures and movies like this 5 minute video. Tom Cruise was roundly criticized by doctors for buying his own ultrasound machine for home use.

Conclusion

There is no reason to fear prenatal ultrasounds that are ordered by science-based medical professionals and performed by qualified technicians, but it seems prudent to exercise caution and not do them for frivolous reasons.

Considering that Anderson practices homeopathy, subluxation-based chiropractic, and craniosacral therapy, disparages drugs, and manipulates the spines of newborn infants, I think her own practices are far more worrisome than the ultrasounds she fears.

 

 

 

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Seven Deadly Medical Hypotheses revisited

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Back in February, Mark Crislip and I both deconstructed an article written by Dr. Reynold Spector that appeared in the March/April issue of Skeptical Inquirer (SI), the flagship publication for the Committee for Skeptical Inquiry (CSI). The article was entitled Seven Deadly Medical Hypotheses, and, contrary to the usual standard of articles published in SI, it used a panoply of spin, bad arguments, and, yes, misinformation to paint a picture of seven horrifically deadly “medical hypotheses,” most of which, even if the reader accepted Dr. Spector’s arguments at face value in a worst case scenario, weren’t actually all that deadly at all, with the alleged deadliness of the others being in dispute. In addition, Dr. Spector painted a picture of medical science that is not nearly rigorous enough. While we at SBM would probably agree that much of medical science is insufficiently rigorous, given how so-called “complementary and alternative medicine” (CAM) or “integrative medicine” (IM) has found a prominent place in medical practice in all too many academic and private medical centers, Dr. Spector got it so wrong that he wasn’t even wrong when he conflated preliminary, hypothesis-generating studies with the big, randomized, phase III clinical trials necessary to achieve FDA approval for a new drug or device. This latest article by Dr. Spector seemed to be of a piece with his previous article in the January/February 2010 issue of SI entitled The War on Cancer A Progress Report for Skeptics, which was so negative in its assessment of scientific progress against cancer that for a moment I was wondering if I were reading NaturalNews.com or Mercola.com.

Unfortunately, Seven Deadly Medical Hypotheses itself is not yet online on the CSI website; so readers without a subscription to SI cannot at the present time judge for themselves whether Mark and I were too harsh on Dr. Spector, but our criticisms, along with that of SBM partner-in-crime Harriet Hall, did have an impact. Seemingly genuinely stunned at the level of criticism leveled at an article published in SI, SI’s editor Kendrick Frazier, to his credit, invited several responses to Dr. Spector’s article, which Harriet Hall, Mark Crislip, Carol Tavris, Avrum Bluming, and I eagerly provided. These letters were originally scheduled to be published a couple of issues ago, along with Dr. Spector’s response. Unfortunately, publishing in dead tree media being what it is, Harriet Hall and I were disappointed to find that the latest issue of SI still didn’t contain our rebuttals. Fortunately, Mr. Frazier has posted this material online for your edification, although, again, I wish he had also published the original article as well.

What other skeptics said about Seven Deadly Medical Hypotheses

Before I deconstruct Dr. Spector’s response to criticism, I think it’s worth briefly commenting on some of the other criticism that Dr. Spector garnered, the first of which appeared in the letters section of the July/August 2011 issue of SI in the form of two letters, one by Dr. James Kolter and one by a professor of social science named Robert J. Miller. Unfortunately, both appear to be primarily single issue critiques, rather than taking on the entire wrong gestalt of Dr. Spector’s article. For example, Dr. Kolter, as both Dr. Crislip and I did in our SBM blog posts, pointed out that the evidence indicting hormone replacement therapy (HRT) after menopause as a cause of breast cancer is not as definitive and clear-cut as Dr. Spector represented it, while Dr. Miller took Dr. Spector to task for a “seeming too-easy dismissal of a positive role of fresh fruit and vegetables in disease prevention.” Both of these are, of course, valid criticisms, but the miss the meta-issues underlying Dr. Spector’s medical pseudoskepticism, one of which Mark Crislip, in his usually insightful manner, picks up on right away:

The article “Seven Deadly Medical Hypotheses” has fundamental flaws. The argument, as I understand it, is that medical researchers fail to use the hypothetical/deductive approach to decide upon research agendas and therefore waste a “vast quantity of resource to disprove them.”

The argument as presented is circular. The author uses information from completed studies to prove the studies should not have been done in the first place. He fails to consider the state of knowledge at the time the studies were done and the cumulative nature of medical knowledge.

Meanwhile, Carol Tavris and Avrum Bluming pointed out a more irritating aspect of Dr. Spector’s entire attitude:

Of course, scientists and other skeptics can and do disagree with one another when it comes to interpreting data. Our primary objection to Spector’s discussion of HRT is not his conclusion but his tone of certainty, his oversimplification of an enormous body of research, and his unwillingness to question received wisdom from the WHI. Even some investigators who share his belief that the relative risks of HRT warrant concern acknowledge that the absolute risks from this treatment are small. In one worst-case analysis, researchers calculated that a fifty-year-old woman taking estrogen and progestin for ten years has a 96 percent chance of remaining free of breast cancer versus a 98 percent risk if she does not take HRT.

I will note that, as a breast cancer surgeon, I do not quite agree with Tavris and Bluming with their apparent glee in trashing the Women’s Health Initiative study that led to the publication of the famous paper in the Journal of the American Medical Association back in 2002 concluding that estrogen/progestin combined HRT increased the risk of breast cancer, a finding that Tavris and Blum apparently do not accept. Of course, this is an example of how scientists and other skeptics can disagree when it comes to interpreting data.

Finally, Harriet Hall, a.k.a. The Skepdoc, weighs in with a devastating characterization of Seven Deadly Medical Hypotheses:

Spector’s article was doubly disappointing because he had so many excellent points that were sabotaged by the way he presented them. Medical science is far from perfect, but it is a cooperative, self-correcting endeavor that constantly criticizes itself and is constantly improving. We need continued rational skepticism and constructive dialog, not oversimplified contrarian polemics.

Dr. Hall nailed it (as usual). Dr. Spector could have made some very valuable points about the complexity and difficulty of interpreting scientific evidence in medicine or in designing clinical trials. Instead, he decided to go all Mike Adams on us.

Since I’m the one writing this particular post, I won’t bother to quote from my own letter in response to Dr. Spector’s article. If you’re enough of a glutton for punishment or for some odd reason need more David Gorski in much the same way that the world needs more Mark Crislip, feel free to read it yourself. Regardless of your opinion of my characteristic verbosity and false sense of modesty, at the risk of using a reverse argumentum ad populum, I will point out that, in the several months since Dr. Spector’s article appeared, I had a hard time finding any medical skeptic with anything positive to say about it. Still, just because Dr. Spector’s article garnered a lot of negative attention in the skeptical blogosphere doesn’t necessarily mean that he didn’t make some valid points. No doubt, if he is as right as his dogmatic certainty would appear to indicate, Dr. Spector will have prepared excellent rebuttals to our criticisms that address each salient point that each of us raised, at least within the space constraints allowed (which, in all fairness, were significant), right?

Wrong.

Dr. Spector doubles down

The first thing I noticed reading Dr. Spector’s response to criticism is that Dr. Spector does not respond particularly well to criticism. Perhaps he should become a blogger. Of course, not responding well to criticism is not necessarily that horrible a thing in and of itself, as long as it doesn’t devolve into never listening to anyone and some well-intentioned criticism can still get through. On the other hand, these latter two conditions can be a death knell for a scientist, because one of the chief skills needed to succeed in science other than the ability to do good science is the ability to handle criticism with grace and to respond to it with evidence. Outside of science, though, the ability to double down when criticized can be a required positive job skill, particularly in politics, public relations, and, of course, punditry. How else can one explain Rush Limbaugh, Sean Hannity, and Ann Coulter? Like Limbaugh, Hannity, or Coulter, Dr. Spector reacts to criticism primarily by doubling down on his previous statements.

The second thing that I noticed in Dr. Spector’s response is that he is the poster child for a common saying we have in medicine that goes something like, “‘Perfect’ is the enemy of the good.” In other words, yes, in an ideal world it would be lovely if every single medical study had a perfect hypothesis and followed the rigorous methodology of the randomized clinical trial analyzed using exactly the correct statistical analysis. However, many questions don’t easily lend themselves to that approach, and, more importantly, I point out again that there is a difference between hypothesis-generating studies, which are generally smaller, less controlled, and sometimes don’t even have a hypothesis at all (after all, they’re called “hypothesis-generating” for a reason) and final, hypothesis-testing experiments and clinical trials that lead up to FDA approval. Both have their role in science, the former early on in the discovery process, the latter after the discovery process is well under way and approaching an actual, usable treatment that needs to be validated in a phase III randomized clinical trial. Also, such a rigid insistence on methodological perfection above all else smacks of what a favorite blogger of mine (alas, now retired) Revere called “methodolatry.” No doubt Dr. Spector would retort that I say that as though it were a bad thing, to which I would respond that it is a bad thing when taken to an extreme and Dr. Spector does take it to an extreme. Each type of study has its proper place in medical research, from basic science, to translational, to animal studies, to preliminary clinical trials, to the final, big phase III trials whose results are used to apply for FDA approval.

Be that as it may, the last thing that comes through in Dr. Spector’s response is that he appears to think that we do not understand his arguments or the basics of medical science. In fact, Dr. Spector arrogantly doubles down on his previously bad arguments while at the same time accusing skeptics of not understanding him:

It is clear from reading these letters that the correspondents do not understand how to evaluate the medical literature—how to discriminate the wheat from the chaff. They do not understand the hierarchical nature of proffered evidence. For example, I doubt any of the correspondents understand Hill’s criteria for assessing causal relationships in epidemiology/observation studies (see below). I recommend they read Spector and Vesell (2006) or the online methodological supplement to my paper on nutrition in SKEPTICAL INQUIRER (Spector 2009). They should also consult the FDA regulations for what constitutes proof in drug development.

I realize that we’re not supposed to use NSFW language here on SBM. Heck, I’m even the managing editor who says that we bloggers are not supposed to use NSFW language here on SBM, with Dr. Novella’s agreement. So instead of saying what I was thinking as I read this paragraph, I will instead say, “What a pair of fetid dingo’s kidneys!” In any case, I’ll simply point out that reading the medical literature and “separating the wheat from the chaff” is part of my job. It’s what I do, both in my “real world” job and as editor and blogger at SBM. Readers can peruse my work here at SBM and judge for themselves whether I (and all the other bloggers) do a good or poor job at it. As for not understanding “Hill’s criteria,” well, I must admit to a tiny chuckle when I read that sentence, given how often we’ve written about it here on SBM in the context of countering the use and abuse of Hill’s criteria by promoters of unscientific medicine. In fact, Mark Crislip, who wrote one of the letters, also wrote a rather nice discussion of Hill’s criteria. While no one would expect that Dr. Spector would have searched SBM for posts on Hill’s criteria, it is rather presumptuous of him to leap to such conclusions based solely on our letters.

It’s also rather presumptuous of Dr. Spector to assume that I (or others) didn’t read any of his other papers. For instance, I read Spector and Vesell (2006). I also read his SI article Science and Pseudoscience in Adult Nutrition Research and Practice. The latter article spent a great deal of verbiage to conclude that “In general, the most powerful method to establish the truth of many nutritional hypotheses, when contributory causality is postulated, is the prospective, randomized, controlled trial.” No kidding. Nowhere in the article, however, does Dr. Spector acknowledge just how difficult, sometimes impossible even, it often is to do a prospective, randomized, controlled trial studying hypotheses involving the role of nutrition in disease. Sure, it’s possible to do for a subset of nutritional trials (supplementation with individual vitamins or nutrients, for instance), but even then it’s not easy. When it comes to more general questions, such as whether a diet rich in certain fruits and vegetables prevents cancer, it might be either too expensive or too difficult to ensure adequate adherence to control and experimental diets, making such a trial impractical or even downright impossible. What would Dr. Spector have us as scientists do when confronting such questions? Throw up our hands and say, “Since we can’t do a rigorous, randomized, controlled clinical trial, I guess we’ll never know the answer”? Apparently so. I would counter: For such questions, science is either forced to use less rigorous methodology and try to determine if there will be a confluence of evidence from a variety of techniques that leads to an answer or give up, and I’m not one for giving up on important questions. Once again, Dr. Spector doubles down:

Three correspondents claim I don’t understand that the evaluation of clinical science is not easy. Gorski talks about the “messiness of science-based medicine.” Crislip states “medicine advances slowly and erratically.” Hall states that “scientists are doing the best they can.” What they do not understand is that one of the reasons for this sorry state of much of the clinical literature is that many published studies do not have a clear hypothesis, are underpowered, or use inadequate methods (e.g., epidemiology/observation studies attempting to “prove” causal connections).

One wonders what Dr. Spector thinks of the epidemiological studies that first demonstrated a causal link between smoking and lung cancer. It’s notoriously difficult (albeit not impossible), for example, to induce lung cancer in experimental rodents using tobacco smoke or extracts from tobacco smoke. It would also be highly unethical to do a randomized clinical trial to test whether smoking causes lung cancer in humans. Seriously. I ask Dr. Spector in all earnestness how he would have demonstrated that smoking causes lung cancer in humans, if not accepting strong results from epidemiological studies as sufficient.

Ironically, Austin Bradford-Hill (yes, that Hill, of Hill’s criteria) was a pioneer in demonstrating the link between smoking and lung cancer, and his criteria came partially out of that work. Teaming up with Sir Richard Doll, Austin Bradford-Hill published a case-control study in 1950 that showed that smoking greatly increases the risk of lung cancer. The two followed up that study with a long-term prospective study known as the British Doctors Study, which followed the health of 30,000 British doctors for several years, which was a prospective cohort study. Neither of these were controlled, randomized clinical trials. In any case, Hill’s criteria were designed specifically to determine when a disease or condition associated with an environmental exposure could be considered to be caused by that exposure, which, of course, can’t ethically be done in general through a randomized clinical trial. Thus, Dr. Spector implicitly recognizes that for environmental exposures causality can be scientifically inferred from a confluence of epidemiology and other evidence. For everything else, apparently, if it isn’t a randomized clinical trial, to Dr. Spector it’s crap. In any case, Dr. Spector seems to leap back and forth between advocating randomized clinical trials for everything and invoking Hill’s criteria, the latter of which do not necessarily require randomized clinical trials specifically, although #8 (experiment) can, depending on the specific exposure, be interpreted as requiring an RCT of some kind. The problem is, again, that because it’s not acceptable ethically to do an RCT for an environmental exposure that results in disease in a lot of questions, Hill’s criteria #8 will automatically go unfulfilled.

Dr. Spector seems particularly stung over the criticisms of his take on hormone replacement therapy, so much so that he spends a considerable fraction of his limited space in answering them, pointing out that estrogen can cause mammary cancer in female rodents (true) and that it can cause uterine cancer in humans (also true). All of this is rather beside main criticisms I had, given that in general I accept that mixed progestin/estrogen HRT increases the risk of estrogen receptor-positive breast cancer, although more recent evidence suggests that estrogen-only HRT probably does not, or if it does it does so so modestly that it is difficult to detect the increased risk in epidemiological studies. I also can’t help but point out that more recent work suggests that in some cases estrogen HRT can be protective against breast cancer. Once again, the evidence is more complex than how Dr. Spector represents it, as this analysis of the Women’s Health Initiative Estrogen-Alone Trial demonstrates.

In any case, Spector’s arguments miss the point entirely, as he piously proclaims:

In fact, I believe a good physician should use only proven therapies for which the risk/benefit ratio favors the patients. That was never the case with HRT, a known carcinogen. Fortunately, when my sister asked me if she should take HRT for her menopausal symptoms in the mid-nineties, I said no; it’s too risky and its benefits are uncertain.

How condescending of Dr. Spector! As if we believe that a physician should use unproven therapies for which the risk/benefit ratio doesn’t favor the patient! (Look for that sentence to be quote-mined some day.) The point was that it wasn’t so clear at the time and medicine has to use the best available evidence that it has at the time. Even now, the situation is not as clear as Dr. Spector makes it out to be.

Finally, I must admit that Dr. Spector truly disappointed me with his last paragraph, where he doubles down yet again, in essence referring readers to an article many of whose points were easily refuted:

To answer the questions on cancer chemotherapy, I recommend my SKEPTICAL INQUIRER article “The War on Cancer” (Spector 2010). Moreover, the problems with chemotherapy keep surfacing. For example, it was shown that for lung cancer patients, hospice care with minimalist chemotherapy was better than standard chemotherapy in terms of both quality of care and longevity (Temel et al. 2010). The scandals associated with the so-called targeted chemotherapy—such as the ineffective, incredibly expensive, and risky Avastin in breast cancer treatment—escalate (Tucker 2011). Finally, the authors of a recent long, thoughtful article (Smith and Hillner 2011) argue persuasively, as I did, that there is tremendous overuse of chemotherapy. The authors point out that “some oncologists choose chemotherapy in order to maximize their practice income. A system in which one half the profits in oncology [practice] are from drug sales is unsustainable.” Where is the well-being of the patient in this? A thoughtful, empathetic reader will weep.

Actually, I suspect that if Austin Bradford-Hill were alive today, he’d weep at Dr. Spector’s obsessive worship of his nine criteria to the exclusion of all else, but I digress.

When called out on his claims, note how Dr. Spector retreats and revises his argument to something that is more easily defensible. Remember, Dr. Spector didn’t argue just that chemotherapy is overused and that it doesn’t do much good in certain circumstances, such as advanced solid malignancies like non-small-cell lung cancer. He went far, far beyond simply suggesting that we need to be more science- and evidence-based in our use of chemotherapy. In fact, let’s revisit what he did say, which was to label chemotherapy as a “deadly medical hypothesis”:

From a cancer patient population and public health perspective, cancer chemotherapy (chemo) has been a major medical advance.

I also note that I spent quite a bit of verbiage in my last post on this issue refuting much of what Dr. Spector wrote in his “war on cancer” article; so I will not repeat it here. I also pointed out how including chemotherapy as a treatment for cancer as one of his Seven Deadly Medical Hypotheses was off-base and exaggerated the problems with chemotherapy as a cancer treatment far beyond the oncological evidence. On the one hand, while it disappoints me that Dr. Spector apparently never bothered to click on the link I provided to my original criticism of his article, it does not surprise me.

As for the rest, Temel et al is a relatively small but nonetheless provocative study telling us something we already know, namely that chemotherapy doesn’t do very much good for metastatic non–small-cell lung cancer, and I’ve already written quite a bit about the problems with Avastin in breast cancer. This is a controversy that has gone both ways in breast cancer even as Avastin has proven value in other cancers, such as colorectal cancer. Again, if all Dr. Spector had argued was that chemotherapy is overused in some cancers, he’d have gotten little or no argument from me. As for what Smith and Hillner actually argue in their NEJM article, it is not primarily that there is huge overuse of chemotherapy, but rather that oncologist behavior should be changed in the following ways:

  1. Target surveillance testing or imaging to situations in which a benefit has been shown.
  2. Limit second-line and third-line treatment for metastatic cancer to sequential monotherapies for most solid tumors.
  3. Limit chemotherapy to patients with good performance status, with an exception for highly responsive disease.
  4. Replace the routine use of white-cell–stimulating factors with a reduction in the chemotherapy dose in metastatic solid cancers.
  5. For patients who are not responding to three consecutive regimens, limit further chemotherapy to clinical trials.

Among other things, they also suggest switching to symptom-directed care when chemotherapy success is highly unlikely. While there is an implication that chemotherapy is overused, the article is more about sticking as closely as possible to science- and evidence-based treatment and recalibrating expectations in order to activate hospice earlier in cases when treatment success can’t be expected. None of these are radical; none of these question the paradigm of chemotherapy use against cancers for which its use is evidence-based. All the authors do is to advocate for integrating hospice care and sticking to evidence-based chemotherapy regimens whose toxicity is lower, all in order to increase the quality of life of cancer patients.

Science: A spectrum of evidence

As I’ve pointed out before, Dr. Spector appears to be someone whose career has been primarily involved in drug development in the later stages. At least, if that’s not the case, I have a hard time figuring out how he can (1) conflate the necessary evidentiary burden required for hypothesis-generating experiments with late-stage randomized clinical trials designed to win FDA approval; (2) lecture critics with a straight face by telling us to read FDA regulations regarding what constitutes proof in drug development and referring us to a paper of his in which he concludes the breathtakingly obvious, namely that the controlled randomized clinical trial is the gold standard for clinical evidence; and (3) dogmatically present a simplified view of scientific and clinical evidence that brooks no ambiguity. All of this bespeaks a narrowness of vision that probably serves him well for defined, limited projects that ask questions like, “How can we design a drug to target this receptor?” and “How do we confirm or refute that the drug works?” However, when it comes to vision that will lead to medical breakthroughs that aren’t simply using existing knowledge to design better new drugs? Not so much, given his obvious contempt for the necessarily less rigorous preliminary studies, the majority of which will fail but a few of which will lead to more rigorous studies demonstrating the efficacy of a new therapy. In other words, sticking to Dr. Spector’s methodology will produce science that is rigorous, safe, and completely uninnovative. I also can’t help but wonder when was the last time Dr. Spector actually took care of a patient, given his obvious intolerance for ambiguity.

No one is arguing against more scientific rigor, least of all me, and where Dr. Spector notes deficiencies in the science being presented that seem reasonable, I’ll be with him. However, when he labels medical hypotheses that are not really hypotheses as deadly when they are not really deadly and then doubles down on the same pseudoskeptical arguments when criticized for them, I’m most definitely not with him there. It needs to be remembered that each of the types of experiments and studies used in science, from small basic science investigations to hypothesis generating genome-wide association studies and next generation sequencing studies of tumors, to the most rigorous phase III clinical trials designed to win FDA approval, are all tools designed to answer specific questions. Each has its place, and a “one size fits all” approach to scientific evidence doesn’t work. Demanding FDA-level evidence for every question makes little sense. This is not a straw man, either; it is what Dr. Spector genuinely appears to be advocating, at least to me. The problem is that Dr. Spector dogmatically clings to the methodolatry of his randomized clinical trials and his FDA regulations in much the same way that a minister, rabbi, or imam holds on to his holy book. That might be a form of science, but it is not good science, and it’s definitely not skepticism, which is why I hope not to see any more of Dr. Spector’s work in SI.

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Verecloud: Tech Partner Spotlight

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Welcome to the next installment in our blog series highlighting the companies in SoftLayer’s new Technology Partners Marketplace. These Partners have built their businesses on the SoftLayer Platform, and we’re excited for them to tell their stories. New Partners will be added to the Marketplace each month, so stay tuned for many more come.
- Paul Ford, SoftLayer VP of Community Development

 

Scroll down to read a guest blog from Verecloud, a technology partner that makes it easier for small- and medium-sized businesses to shop for, select, purchase, manage and monitor the performance of their cloud services and related spending. To learn more about Verecloud, visit http://verecloud.com/.

Cloudwrangler from Verecloud

Ubiquitous Internet access and technological advances in virtualization and IT management have caused an explosion in the availability and adoption of cloud services. Just a few years ago, it would take hours – if not days – to activate a new cloud service for a customer. SoftLayer can now perform this feat with servers in minutes, and other providers of email, CRM and accounting solutions have equally fast turn-up times.

The cloud gives small- and medium-sized businesses (SMBs) access to enterprise grade technology so that they can compete more effectively with little, if any, capital investment, so those SMBs are prime consumers of cloud services. By moving to cloud services, their businesses gains flexibility and affordable scalability to throttle their infrastructure and services up and down as their business grows, changes, moves locations or becomes more mobile.

Even with all of those benefits, adding a little cloud here and a little cloud there ends up making it difficult for these SMBs to manage all of the disparate services. Who is paying for what? Are they accounted for in expense reports? How can you allocate the costs to your sales, marketing, operations or support departments? Is IT aware of all of the cloud services? What happens if someone leaves the company and you need to deactivate their access and reassign all of their data to other employees?

Verecloud’s answer to all of these questions is the Cloudwrangler app store for small businesses. Simply put, it is a single source for SMBs to discover, buy, use and manage their cloud services. This platform makes finance happy since they can properly track and manage costs. IT is happy because they are aware of all the services being used in the company and can manage them from a single control panel. HR is happy because they can monitor and regulate employee access when necessary. Everyone is happy.

Verecloud is proud to feature SoftLayer as a key partner and suppler in the Cloudwrangler marketplace (which also happens to be powered by SoftLayer’s CloudLayer Computing). In addition to the infrastructure piece, we offer business class email, backup and recovery, and collaboration capabilities that can be incorporated quickly, seamlessly and affordably into any business:

Cloudwrangler Services

We’re staying busy building out more features and functionality to the Cloudwrangler marketplace, and we’re excited about the partnerships we’ll make as we keep the community growing. If you’re interested in learning more about Cloudwrangler, visit at Verecloud.com today.

-Russel Wurth, Verecloud

The Importance of Network Security

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On Friday, April 27, 2011, I powered on my Sony Playstaton 3 and prepared to sit down for an enjoyable gaming session. As a Sony customer and a PlayStation Network (PSN) user, I expected my system to be able to connect to a service that I was told would be available. Because I had to sign an agreement to join the PSN, I expected my personal information to be secure. On that morning, I logged in and had no idea that my personal security might be at risk due to a lack of tight-knit practices and possible information redundancy.

My many years of brand loyalty held strong as I was told constantly that the PSN was down as a result of a maintenance. I understand that emergencies happen and proper planning by a professional company is in place to shorten the duration of impact. As it turned out, proper planning for this type of event seemed to have been lost on Sony. A malicious security cracker was able to infiltrate their network to gain access to numerous PSN customers’ sensitive personal information. This kind of blunder had every PSN customer wondering what could be done to prevent this kind of event from happening again.

You probably noticed that I used the word “cracker” as opposed to the more common “hacker.” A hacker is an extremely knowledgeable person when it comes to computers and programming who knows the ins and outs of systems … which is completely legal. The typical misconception is that all “hackers” are engaged in illegal activity, which is not true. If the hacker decides to use these skills to circumvent security for the purpose of stealing, altering and damaging (which is obviously illegal), then the hacker becomes a cracker. To put it simply: All crackers are hackers, but not all hackers are crackers.

When I started working at SoftLayer three years ago, I was told to pay very close attention to our company’s security policy. Each employee is reminded of this policy very regularly. Proper security practice is essential when dealing with private customer data, and with the advancement of technology comes the availability of even more advanced tools for cracking. As a trusted technology partner, it is our obligation to maintain the highest levels of security.

There is not a day at work that I am not reminded of this, and I completely understand why. Even at a personal level, I can imagine the detrimental consequences of having my information stolen, so multiply that by thousands of customers, and it’s clear that good security practices are absolutely necessary. SoftLayer recognizes what is at stake when businesses trust us with their information, and that’s one of the big reasons I’m to work here. I’ve gone through the hassle and stress of having to cancel credit cards due to another company’s negligence, and as a result, I’m joining my team in making sure none of our customers have to go through the same thing.

-Jonathan

Global Expansion: An Early Look at Singapore

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Based on the blog’s traffic analytics, customers are very interested in SoftLayer’s global expansion, and in my update from Tokyo, I promised a few sneak peeks into the progress of building out the Singapore data center. We’ve been talking about our move into Asia for a while now, but we haven’t showed much of the progress. The cynics in the audience will say, “I’ll believe it when I see it,” and to them, I say:

These pictures were actually taken a few weeks ago before our Server Build Technicians came on site, and it looks even more amazing now … But you’ll have to check back with us in the coming weeks to see that progress for yourself. Both the Singapore and Amsterdam facilities are on track to go live by the middle of Q4 2011, and we’re already starting to hear buzz from our customers as they prepare to snatch up their first SoftLayer server in Asia.

If you want to have a little fun, you should compare these build-out pictures with the ones we’ve posted from the completed San Jose facility and the under-construction Amsterdam data center. As we’ve mentioned in previous posts, SoftLayer uses a data center pod concept to create identical hosting environments in each of our locations. Even with the data centers’ varying floor plan layouts and sizes, the server room similarities are pretty remarkable.

Stay tuned for updates on the build-out process and for information about when you can start provisioning new servers in Singapore. If you have any questions about the build-out process, leave a comment below or hit us up on Twitter: @SoftLayer.

-@toddmitchell