Lab Soft News

An Example of a Government-Sponsored Central Medical Information Repository

In a recent note, I proposed the idea of developing cloud-based central repositories to store radiology reports and images as a way to avoid redundant testing. Before new studies were ordered for patients, at least in theory, such repositories could be queried to search for prior studies. My note was prompted by a comment to a previous note discussing the increasing cost of imaging studies in the U.S. Mark Cox, an astute observer of the global LIS industry who works for Sysmex in New Zealand, responded to my second note with the following comment:

In NZ this is a key focus and justification for a number of projects. Have a look at http://www.testsafe.co.nz/ & http://www.testsafe.co.nz/images/testsafe_diagram_webready.png This is a system set up that contains all pathology (hospital and community), and radiology [reports] for a region. In this case Auckland with a population of 1M. Soon to be added is community Pharmacy dispensing which will have all drugs ordered by a GP and dispensed at the local pharmacy. One of the key justifications for this project was retesting when patients moved from one hospital to another or from secondary to primary care....[T]his is one of the big advantages of living in a socialised environment where the government can invest in regional clinical data repositories.

Here is summary of the New Zealand TestSafe central repository copied from his first link:

TestSafe is part of a regional initiative by the three Auckland DHBs [District Health Boards]...to improve information sharing among community and hospital healthcare providers for the benefit of patients. TestSafe gives healthcare providers access to diagnostic results and reports for their patients. It brings together results from DHB facilities and community laboratories and work is underway to include medications dispensed by community pharmacists. TestSafe helps healthcare providers 'complete the picture' so they provide the best care to their patients.

When I previously raised the topic of centralized health data repositories, I purposely avoided a discussion of exactly who (i.e., what authority or organization) would provide such a service. Although the federal government in the U.S. would seem to be a likely choice, this seems to be highly unlikely to me. Firstly, the government will have its hands full for at a decade or more delivering on its promise of guaranteed healthcare for a wider swath of the population . Secondly, I am not sure that a large percentage of our population would feel comfortable with the government holding their health records, although I personally think that it would be a more reliable steward than certain health insurance companies. At least one of the latter does not have an enviable record of being a good steward of such data. I don't know to what extent we can learn from the New Zealand experience. The country had a total population of only 4,143,279 in 2006 -- fewer people than live in some of our major cities. One promising sign of progress in this area is that there is a large and growing literature in radiology about image exchange.

Google as an Enabler and Protector of Global Information Exchange

Having recently posted my personal reaction to the tiff between Google and China, the evolving global role of the company is uppermost in my mind (see: A Few Suggestions about Google's Long-Term China Strategy). I had been worried that most of the media savants were clueless about what had caused this disagreement until I read David Carr's recent column in the New York Times (see: Not Creating Content. Just Protecting It.). It's one of the most perceptive analyses about Google that I have read to-date. Below is an excerpt from it:

Should we be surprised that the biggest fight over freedom of expression in years involves Google, a company that produces algorithms rather than articles? Probably not. Google executives struck a blow for free speech in China last week when they announced they were moving their service to Hong Kong after a series of mounting conflicts with the government over the privacy of its users and the free flow of information. That would seem to put Google in league with newspapers, television news divisions and other outlets that look to protect information from government control. But no, Google insists, it is definitely not a media company....But regardless of how it defines itself, Google has come to grips with its role as both enabler and protector of the global exchange of information....By espousing traditional journalistic values like openness, transparency and access, the company is walking away from the largest Internet market on the planet in the hopes of putting pressure on China’s government....That’s not to say Google doesn’t see this as good business ultimately: the company wants consumers to believe its searches are free from commercial and political agendas....Google has shied away from the media label, and for good reason. Already, Italian courts have held three Google executives criminally liable in an invasion of privacy case over an offensive video on YouTube. Among other arguments, the courts held that because Google monitors and censors search results in China, it could be expected to observe community standards in Italy. Australia, South Korea and other countries are also looking to Google to exercise editorial control over its Web products....In China, Google and other Internet companies act as virtual publishers for millions of people using the Internet to connect with others and to question the excesses of their government. In a sense, Google is championing the rights of all the citizens of the Internet kingdom.

This article begins to address some of the key questions that we are facing in the internet era such as the following: What is a publisher? What is a virtual publisher? What is content? What is a media company? Should virtual publishers be required to pay for content? How does protecting content and providing access to it differ from publishing it? What is censorship? To what extent do western democracies practice censorship? Is content search on a global basis more important than the creation of the original information? To what extent does open internet search destabilize totalitarian countries like China?

China is only a very small portion of Google's advertising business today. Europe, on the other hand, provides a major component of its revenue stream and can only grow in the future. I had missed a key point about Google's reaction to China's demand that it censor its search functions on the basis of government requirements. If the company allowed itself to bow to the censorship demands of China, it would need to do likewise for democratic countries such as Italy, Australia, and South Korea. I had pointed out in my previous note that Google was actually pursuing its long-term strategic interests by pulling out of China. This idea now seems to be even more relevant. And in so doing, it is also providing a benefit to its internet search rivals that are currently cowering in the background.

A Suggestion for Decreasing Unnecessary Radiology Studies

In a recent note, I raised the issue of how the rapidly increasing number of medical imaging studies was raising the cost of care. I must admit that I was very pessimistic about most efforts to "bend the curve downward" and listed a number of reasons for my position (see: CTs, MRIs, and PET Scans Drive Cost of Healthcare Upward). A reader, Jackie Walsh, responded with an interesting and practical comment:

Bruce, I agree that it will be hard to reverse this trend for the reasons you state. However, there is a category of imaging exams that can be reduced to offset the overall growing volume. That is the percentage of exams that are ordered simply because a similar or recent exam for the same patient isn't accessible (perhaps because it lives within the firewall of another hospital, or was burned to a CD and from some technical reason is inaccessible). In the US it has been estimated that over 10% of all diagnostic exams may be wasteful duplications because physicians do not have access to their patients’ previous records. This waste is costing billions of dollars annually and some patients are exposed to excessive radiation as a direct result of redundant exams. This is part of the overall cost of diagnostic imaging that we could really tackle.

Jackie's idea deserves serious discussion. Most hospital-based personal health information (PHI) is not particularly portable and cannot easily be reviewed if a patient is admitted to a different health system than the one in which the electronic records were initially generated and stored. She refers to such information as "living within the firewall of another hospital." I will include within this PHR category the radiology reports, residing on the first hospital radiology system (RIS), and the images themselves that reside in the first hospital PACS. When a patient is admitted to a new hospital, it is both possible and recommended that a CD be obtained from the previous radiology department and carried to the new one so that they can be reviewed. It may be possible to avoid redundant radiology studies if this latter step is taken. One would think that the burden of responsibility should fall on the original hospital to transfer a patient's records and images when notified of a status change but I fear that it's the patient who usually needs to perform this task.

In the future, a solution could be devised to correct this medical imaging access problem to avoid rework. If Jackie's assertion above that some 10% of all imaging exams are redundant, such a solution could result in substantial cost savings. Recall that I have posted a number of previous notes about cloud storage, which is particularly relevant for radiology images. A suitable solution for this problem would be a national central image repository for radiology reports and images using cloud storage. An accompanying metafile could contain patient demographic data plus the date and type of all radiology studies performed in the U.S. for, say, the last decade. When a patient is admitted to a U.S. hospital, a query could be automatically generated to this metafile to quickly determine whether there was a record of any recent imaging studies for that patient. If the records show the existence of such studies and with proper permission, the images themselves could be downloaded to the requesting facility. This approach would not solve the need for overreads, where the new hospital policy would require that their radiologists review the newly downloaded studies to determine whether there is agreement with the previous reports.

A Few Suggestions about Google's Long-Term China Strategy

By now, most people have heard that Google is disengaging from its search business in China, one of the largest markets in the world. The reasons for this action are, first, that China is requiring Google to censor web search for clients in the country. Secondly, Google is stewing about cyberattacks on its software originating in China that may have had government sponsorship. These points, plus others, were detailed in the recent news story focusing about Sergey Brinn, one of the founders of the company (see: Brin Drove Google to Pull Back in China; subscription required).Below is an excerpt from the story:      

Google Inc. co-founder Sergey Brin pushed the Internet giant to take the risky step of abandoning its China-based search engine as that country's efforts to censor the Web and suppress dissidents smacked of the "totalitarianism" of his youth in the Soviet Union....On Jan. 12, Google said it would stop self-censoring its search engine in China, citing a major cyberattack that appeared to target the email of human rights activists. On Monday, Google began routing mainland Chinese users of its search engine to a site in Hong Kong that the company isn't censoring....The move appears to have left Google's China business in jeopardy. On Wednesday, China Unicom Ltd., the country's No. 2 mobile-phone operator, said it wouldn't install Google's search functions into new handsets given its decision to stop censoring. Google employees in China are contemplating defecting to rivals such as Microsoft Corp., according to recruiters....Mitch Kapor, a Silicon Valley venture capitalist, said Google's moral stand made sense long term, because China will eventually get more open....Whether others will follow Google remains unclear....Mr. Brin sees Google's China stance as a signal to other countries....The 36-year-old co-founder said he was moved by growing evidence in China of repressive behavior reminiscent of what he remembered from the Soviet Union.

Here are some my personal reactions to this truly astonishing event:

• This is a prime example of a global corporation functioning as a kind of super-state, placing its short-term profits at risk by drawing a line in the sand for a totalitarian regime.The Chinese technocrats must be shaking their heads in bewilderment. No world government of late has shown such resolve.
• In taking this action, Google's has displayed more cohones than one might expect from even a powerful sovereign state and particularly from the United States. Veteran diplomats around the world must be hyperventilating at the hubris of a company, even one with a market cap of some $180B.
• Unbelievably, Brin, the co-founder, states publicly for the record (see above) that Google's response to China's bullying can be attributed, in part, to his personal experience living in totalitarian state. Again, a burst of honesty that must be making diplomats cringe.
• In my opinion, Brin and Google have a deeper understanding of the true value of information in today's world, most particularly in China, than most governmental officials. I believe that, in the long run, China will soften its stand toward Google and hand the company both a moral and financial victory. To do otherwise will risk an upheaval of its growing educated class.
• I reject the idea that this initiative by Google is motivated primarily by ethical and moralistic goals. People often mockingly refer to the company's code of conduct: Don't be evil. Rather, I think that Brin and other Google executive believe that their action vis-a-vis China will be good for their business in the long-run. Such long-term thinking has gotten Google where it is today and the leaders of the company are still thinking along these same lines.

CTs, MRIs, and PET Scans Drive Cost of Healthcare Upward

The point is frequently made in the media that the cost of imaging studies is a significant and growing percentage of the total cost of healthcare. It's useful to put some numbers to this assertion. A recent blog note by KevinMD raised the issue (see: How CTs and MRIs drive health care spending). Here's his note in its entirety:

It’s well known that the use of imaging scans, like CTs, MRIs and PET scans, have been growing at an alarming rate. But a recent study provides some stark numbers (see: MRIs, other scans quadrupled in recent years). According to a recent CDC report, “MRI, CT or PET scans were done or ordered in 14 percent of ER visits in 2007, the report from the Centers for Disease Control and Prevention found. That’s four times as often as in 1996.” Although a physician called that growth “astounding,” it’s really no surprise. Emergency departments are becoming more crowded, and with patient satisfaction scores becoming more influential in financial incentives for physicians, sometimes just ordering a test is the path of least resistance. Factor in the specter of defensive medicine, which, according to a survey from the Massachusetts Medical Society, accounts for up to 28% of tests ordered, it’s a wonder that more scans weren’t ordered. Imaging scans are clear cost driver in health care, contributing $12 billion to Medicare’s bill. But costs won’t resonate with patients requesting the tests, or the doctors ordering them. One encouraging sign is the recent trend of publicizing the harms of scans, like radiation from CTs. I’m finding that patients are becoming increasingly aware of the risk, and making a more informed decision after I explain it to them. It’s a small step forward.

Dr. Kevin raises most of the key factors that contribute to the increasing use of CTs, MRIs, and PET scans in our healthcare delivery system. I will add a couple more ideas to his list: (1) imaging technology is truly outstanding and improving -- clinicians increasingly rely on it to arrive at most diagnoses and to rule-out others; (2) patients, in turn, expect their physicians to order these studies when they are being seen in the office and the ER; (3) physicians are reluctant not to order imaging studies for fear of missing a diagnosis, described above as defensive medicine; (4) imaging studies are often formally incorporated into the standard workup of patients with non-specific complaints such as chest pain, joint pain, or headaches; (5) hospital administrators and physician executives have few incentives to attempt to tamp down the ordering of imaging studies because they constitute a major profit line in the hospital budget; (6) the ordering of CTs, MRIs, and PET scans can facilitate the workflow of patients through busy clinics by generating objective, actionable reports.

I think that it will be extremely difficult to reverse the trends listed above because residents and medical students are adopting these practice patterns during their training years and will adhere to them closely throughout the rest of their careers. I believe that recent reports about the harmful effects of cumulative radiation doses from imaging studies will reach the level of consciousness of only a small percentage of patients, most of whom will probably feel that the small risk is worth it. Look for an even a higher percentage of healthcare dollars in the future to be allocated to imaging studies.The federal government, as the major payer for healthcare, will attempt to bend this curve downward but will meet with little success.

March Issue of "CAP Today" Available On-Line

CAP Today recently deployed new technology allowing readers to leisurely page through the electronic version of its tabloid hardcopy publication as if they had a physical copy in their hands. The March issue is now available on-line. If you are shopping for a new anatomic pathology LIS (AP-LIS) or merely want to review the range of such products available in the market, check out the Annual Survey of Anatomic Pathology Computer Systems on page 18. No other survey in the country comes even close to this one. You may also want to look at the first full-page advertisement for the upcoming Pathology Informatics 2010 conference on page 59. This new conference, created by the merger of APIII and Lab InfoTech Summit, will be held on 19-22 September, 2010, at the Westin Copley Place Hotel in Boston. A total of 33 exhibitors have already committed to participate in the event.

Reducing Wastage of Blood and Blood Products in Hospitals

There are two basic ways to reduce wastage of blood and blood products in hospitals. First and focusing on processes that are internal to the blood bank, improved inventory control can reduce outdating of blood. One example of such a process is the maximum surgical blood order schedule (MSBOS) (see: Hospitals Seek to Limit Blood Transfusions as a Cost-Saving Measure). The MSBOS has been widely used and accepted around the world for 35 years. A second approach is to persuade or apply pressure on blood-transfusing physicians to alter their clinical transfusion criteria such that the blood or blood products they would normally transfuse in marginal cases are eliminated. Not only does this latter approach save money, it also conserves scarce resources and reduces the health risk for patients of transfusion-associated infectious diseases. Columbia Healthcare Analytics offers consulting services to hospitals and pathologists for reducing inappropriate blood use by clinicians. Here's a summary of their services copied from the company's web site:

Columbia Healthcare Analytics...provides web-based Interactive External Utilization Review (IEUR) of hospital blood usage and other resources, including peer review, for the healthcare industry. [The company] has re-engineered UR and peer review through innovative use of information technology. Our solutions replace ineffective business processes that restrict healthcare organizations from achieving optimal and cost-effective patient care. Our innovative information technology...permits CHA to review all events, whether it be UR of all blood transfusions, diagnostic test orders or chart documentation. Effective 100% UR results in immediate reduction of resource usage, as high as 15% in the first few months. Immediate reduction of resource usage and reasonable CHA fees create a virtually instantaneous return on investment for healthcare clients.

Here's a summary of the fee structure for CHA consulting services:

A number of hospital charts are selected at random. Typically IEUR of 100 charts is recommended, but as few as 20 charts or as many as one month’s sample may be selected. The fee for Phase I is $190 per chart. This includes a critique of each chart, the results of which can be reviewed by the hospital, the transfusion committee, each department chair and each involved ordering physician..... Potential systemic hospital utilization problems are identified, as well as constructive feedback provided on individual cases to improve physician practice. It is anticipated that this feedback alone may reduce blood usage by at least a few percent, which more than pays for the $19,000 fee to perform a 100 chart review. Upon completion of Phase I, a proposal with detailed cost-benefit analysis will be submitted to the hospital to perform Phase II UR.

If you were to ask me what would happen to blood utilization in a hospital in the midst of an external (or internal, for that matter) review of blood transfusion practices, I would say that it would be immediately reduced by at least ten percentage points. This, in fact, is roughly the assertion made by Columbia in their web site for their "exploratory utilization review" stage. Additional costs are incurred for the following intensive and maintenance utilization reviews, also detailed on the web site. So far, so good.

If the leadership of a hospital pathology department has a desire to decrease blood wastage, it seems to me that the first logical step would be to improve internal work flow processes including inventory control. If there is the political will and mandate to also examine the transfusion practices of the blood-ordering physicians in the hospital, a case can be made for using the services of consultants from CHA. If such scrutiny causes political backlash among hospital physicians, the pathology department can distance themselves from the results with a loss to the institution of only the CHA consulting fees.

I personally would recommend instead an internal hospital-wide review of clinical transfusion practices. Such an "internal dialogue" could result in useful information about the transfusion needs and habits of clinicians, particularly surgeons, and produce gradual changes in behavior without the fear of penalties for non-compliance. Such a process would be harder to walk away from than recommendations from an external consultant, who could be said to lack an understanding of "local medical practices."

Web-Based Genomic Testing Sites Fail to Attract Large Paying Audience

Web-based genomic testing sites such as 23andMe and Navigenics have faced a number of barriers in order to attract clients including a high test price and a complex information product. It should therefore come as no surprise, as detailed by a recent article, that these companies have had difficulty in attracting paying customers (see: Consumers Slow to Embrace the Age of Genomics). Below is an excerpt from it:

Connected to Google by both love and money, 23andMe seems the epitome of a 21st-century company — a cutting-edge merging of biotechnology and the Internet, with a dash of celebrity thrown in. The scarce ingredient so far is customers. 23andMe is the most prominent of a trio of companies that in 2007 began using the Web to market personal genomics services. The companies scan people’s DNA, promising to tell them their risks of getting dozens of diseases. Propelled by its co-founder Anne Wojcicki, the wife of Google’s billionaire co-founder Sergey Brin, 23andMe attracted attention by holding swanky “spit parties” where people gave saliva samples for DNA analysis....But for the common consumer, 23andMe’s service — and those from its main competitors, Navigenics and DeCode Genetics — have been a much harder sell. Two and a half years after beginning its service, 23andMe has only 35,000 customers. And at least a quarter of them got the service free or for only $25, instead of the hundreds of dollars on which the business model is based. Navigenics and DeCode have even fewer customers. The low turnout suggests that many people have not yet embraced the genomics age — despite efforts by the companies to present genetics in an understandable and even entertaining way. It does not help, either, that the services cost $300 to $2,000 and have been trying to catch on during a severe recession. But the services face an even more fundamental problem: in most cases, the current level of DNA scanning technology and science is unable to offer meaningful predictions about the risk that a person will get a disease.

I have been a strong advocate for direct-access-testing (DAT) whereby consumers order and pay out-of-pocket for common lab tests on the web without a physician intermediary. Although the demographics of DAT customers are not widely available, I know that they generally skew toward an older and more affluent population. I suspect that many of them have health insurance so that their interest in monitoring their health is prompted, in part, by convenience factors. The cost of such testing is generally low and test result interpretation (e.g., cholesterol levels) is not particularly challenging.

It should come as no surprise that 23andMe has generated abundant media and venture capital attention given the identity of its co-founder and well as the continuing interest of the media in genomic testing (see: Celebrity Endorsement" of Genomic Testing on the Web). Clinical lab professionals are generally not accustomed to this much attention. I think that it's fair to say that the genomic testing industry has suffered as a result of this media hype and thus far been unable to deliver actionable test results that can justify the cost of testing for most clients. However, I think that it's time for all of us to take a deep breath and reduce our expectations. The science will soon catch up with its diagnostic potential. However, an interesting question to ponder is whether genomic testing will totally revert to hospitals and doctors' offices or whether there is a future for genomic testing sites on the web. After all, DAT itself continues as only a minor niche in the clinical lab industry as a whole.

Health Systems Use Their Regional Dominance to Muscle Insurance Companies

Our healthcare reimbursement system is broken and evidence for this keeps accumulating (see: Why the Prices Charged by Hospital for Inpatient Care Are Irrelevant). I am not sure that healthcare reform will do anything to remedy this situation. The amount of money that insurance companies reimburse hospitals for services is determined by high-level yearly negotiations. These discussions are far removed from the cost of the set of services that are delivered to individual patients. If you don't have insurance and are required to pay the fictional posted list prices, you may be forced into bankruptcy. A recent article raises a new and interesting point about these negotiations (see: Health Insurers Toughen Stance in Disputes Over Hospital Rates). Below is an excerpt form it:

Health insurers are fighting demands by hospitals for sharply higher reimbursement rates by threatening to drop the hospitals from their health-plan networks, and blaming them for higher insurance premiums....In a fresh battle, Stellaris Health Network....just asked a unit of health insurer WellPoint Inc. to increase its payments by 16% this year—in part, so that Stellaris could fund a new cancer center, according to the insurer. The hospital's contract is set to expire at the end of the month, and WellPoint's Empire BlueCross BlueShield unit is pushing back. It sent letters to members on March 2 warning them that the insurer might lose the hospitals from its network....Last week, Continuum Health Partners, a coalition of five New York City hospitals, resolved a protracted dispute during which UnitedHealth Group Inc. said the hospital initially asked it to raise payments by 40%. During the negotiations, UnitedHealth had warned its members that the contract with the hospitals was at risk....Hospitals argue that low Medicare rates and cuts to Medicaid mean that hospitals have to get money from elsewhere, and increasingly that is private insurers. Rising ranks of uninsured Americans have led to more uncompensated care and have swelled the rolls of Medicaid, exacerbating the problem. But insurers contend that in recent years big hospital systems have been buying up smaller medical centers and using their dominance in a region to demand big rate increases. America's Health Insurance Plans, a trade organization, points to data showing hospital markets are 47% more concentrated than they were 13 years ago.

There is increasing consolidation of the health insurance market with Aetna, UnitedHealth, and WellPoint being three of the major players (see: Health insurance industry consolidation a potential threat to providers). As the news clip above indicates, hospitals are being squeezed by cuts in Medicare and Medicaid payments enacted in order to make the cost of healthcare reform more palatable to the public. Hospital executives, seeking to shore up their financial spreadsheets, are seeking large increases from the insurance companies. Part of their demand for revenue is designed to fund new building programs, also as noted above.

Partly in response to the enormous buying power of the health insurance giants and partly to justify their large salaries, hospital system executives are expanding their own empires. This regional dominance provides them with the ability to exercise more influence over a UnitedHealth or Aetna at the bargaining table. What worries me is how little the interests of healthcare consumers such as small business owners are represented in these discussions. The federal government can and will demand low rates for the services it covers. The health insurance companies, perhaps in league with the hospital executives, agree to higher reimbursement rates each year, in part to compensate for the lower rates offered to the government. The net result of all of this is that private employers, and their employees, end up paying the lion's share of the true cost of healthcare.

FDA Studying Approval of Drug Cocktails for Life-Threatening Diseases

In a major policy shift, the FDA is opening the door for the future approval of drug cocktails to treat life-threatening diseases such as tuberculosis in a more effective way (see: FDA Is Easing Way for Drug Cocktails; subscription required). Below is an excerpt from the article:

The Food and Drug Administration is devising guidelines that could accelerate testing and approval of multidrug regimens for some of the world's most deadly diseases....Many diseases, such as AIDS, tuberculosis and cancer, require multidrug combinations. Such drug cocktails can prevent the development of drug resistance, because the microbe or cancer cell needs to undergo more mutations to escape several drugs than to escape just one. By attacking the disease in different ways, drug combinations also improve the chances of therapeutic benefit. Traditionally, the FDA has required each new drug to be tested and approved individually. Afterwards, multidrug regimens are usually developed through additional, time-consuming clinical trials. At least since the mid-1990s, when cocktail therapies slashed the death rate from AIDS, the agency has been urged to streamline its approval process for multidrug regimens....Now the FDA is drafting guidelines on how testing and approving multidrug cocktails composed of new, experimental drugs—something the agency has never done before, according to an FDA spokeswoman.....The new guidelines would apply only to medications for life-threatening illnesses for which good treatment options do not already exist, and for which drug combinations—as opposed to single agents—are believed to be necessary....Testing drugs together can make it more difficult to tease out which drugs or drug interactions cause certain side effects.

This article mentions regulatory science, a term with which I was not familiar. It turns out that academic degrees are now being offered in this field. I am sure such graduates will be cordially welcomed by both the FDA and by the pharmaceutical companies on a much larger scale. One of the core competencies of such companies is the ability to maneuver through this complex bureaucratic pathway. Less time and effort to achieve drug approval equals less cost for them in bringing a drug to market. Knowing how difficult it is to gain FDA approval for new drugs, I can only imagine how complex a process it will be to study new compounds that are administered in combination with other agents. It's a bit of an understatement to say, as above: testing drugs together can make it more difficult to tease out which drugs or drug interactions cause certain side effects.

I can't resist pointing out the analogy of between multi-drug cocktails and the development of panels of biomarkers interpreted by a computer algorithm that the FDA refers to as IVDMIAs. The attempt by the FDA to regulate them has been challenging for the agency. The second draft version of guidance dates back to July, 2007. In my mind, we are now facing a future with both therapeutic cocktails and diagnostic cocktails. This perhaps is a reflection of modern life and modern medicine whereby a single drug or a single biomarker no longer suffices. And the FDA is being forced to operate as a regulatory agency in this new environment. One of the gnarly issues associated with IVDMIAs has been proving diagnostic efficacy. Both efficacy and safety will be even a greater challenge on the drug side of this equation.