From Phenotype to Genotype: Amersham Health Paves the Way

June 1, 2002
Joanna Breitstein

Joanna Breitstein is a contributor to Pharmaceutical Executive.

Pharmaceutical Executive

Pharmaceutical Executive, Pharmaceutical Executive-06-01-2002,

Terminally ill patients often wonder about the roles of timing and fate in determining their life's course. If only they had been tested or diagnosed earlier; if only the doctors had found the tumor before it metastasized. As purveyors of science and administrators of public health, the world's pharma companies and physicians struggle to intervene earlier-indeed to predict and prevent disease-before it's too late.

Terminally ill patients often wonder about the roles of timing and fate in determining their life's course. If only they had been tested or diagnosed earlier; if only the doctors had found the tumor before it metastasized. As purveyors of science and administrators of public health, the world's pharma companies and physicians struggle to intervene earlier-indeed to predict and prevent disease-before it's too late.

CEO John Padfield (left), Daniel Peters, president, global medical diagnostics (center) and William Clarke, MD, MSc, executive vice-president, R&D, (right) steer Amersham Health into the new era of "predict and prevent."

Genomics seeks to answer patients' questions: Why me? Why now? By determining human genetic predispositions, monitoring disease, and prescribing appropriate treatment, researchers and doctors can alter patients' fate through timely diagnosis. Amersham, a world leader in developing tools for the genomics revolution, is at the forefront with products that may change the current healthcare paradigm. Although it has little name recognition within the industry, Amersham has appeared on pharma's radar screen, not so much because of who it is but because of the way it purports to reshape the traditional healthcare model from "diagnose and treat" to "predict and prevent." (See "A New Pardigm,") Indeed, diagnostic agents will illuminate genomics the way it illuminated anatomy: by making genes, which were once invisible, visible.

Leading that charge is Amersham Health CEO John Padfield, PhD, head of the company's diagnostic imaging business and architect of the business' impressive growth. Padfield, along with Daniel Peters, president, medical diagnostics, and William Clarke, MD, MSc, executive vice-president, R&D, met with PE in the New York-Presbyterian Weill Cornell Medical Center to view the department of radiology's new ultra fast computed tomography (CT) machine. Padfield, whose proven acumen for creating partnerships is tempered only by his disarmingly easygoing manner, says the secret to his success is to use his "two ears and one mouth in proportion." The articulate Welsh businessman is working on bridging the link between diagnostics and therapeutics now, to make personalized medicine possible in 20 years. By doing so, the company may be the first to offer paired diagnostic and therapeutic products-and succeed in giving the right treatment to the right patient at the right time.

A New Paradigm

History of Change

Amersham is no new kid on the block. Its roots began in 1940, when the British government established the Radiochemical Centre in a farmhouse in Amersham, United Kingdom, to refine radium used in luminous paint for ship and plane dials during WWII. By 1950, that mission changed to reflect peacetime applications, and the company turned to researching and supplying radioactive isotopes for pharma and other industries. Renaming itself Amersham International in 1977, it made history in 1982 by becoming the first company under British Prime Minister Margaret Thatcher's government to become privatized. After a dizzying spree of mergers, acquisitions, and divestments, Amersham eventually became a powerhouse of artillery for the genomics revolution. In addition to a long list of "firsts," the company boasts that someone somewhere in the world uses an Amersham product every other second.

Its most recent and far-reaching reorganization took place in 1997, involving Amersham International, Pharmacia Biotech, and Nycomed. That year, Amersham's healthcare business merged with Nycomed's imaging business, forming Nycomed Amersham Imaging, and Amersham's life sciences business joined Pharmacia Biotech to create Amersham Pharmacia Biotech. Shortly before buying out Pharmacia's remaining 45 percent stake, the company rebranded itself under one identity, Amersham, and renamed its two businesses Amersham Health (AH) and Amersham Biosciences.

AH develops and manufactures diagnostic pharmaceuticals that allow physicians to visualize all elements of the human body, from organs to molecules, as well as a line of immunotherapy products. It makes up the lion's share of the company's business, accounting for 58 percent of its sales and 77 percent of its operating profit. Amersham Biosciences manufactures gene-sequencing machines as well as other "pick and shovel" equipment for drug discovery and development.

"We were years beyond the merger, and everybody in the company was waiting for a new brand, so there was great energy behind the change," says Padfield. "We've gone from strength to strength since that time."

Although London-based analysts question whether Amersham's business units, with their lack of common products, should be two separate companies, Padfield is certain the synergy lies in the future: "In talking to our colleagues in Biosciences, we are well aware of the possibilities technology offers and what changes in gene-based diagnostic tests might come through. Who knows? We may have our genetic sequence on a computer chip or smart card in ten years. Therefore, we make sure that our work complements advances in technology."

Sales Drivers

Amersham Health is an undisputed leader in the global diagnostic market and the top provider of x-ray, ultrasound, and nuclear imaging agents, the latter for use in spectroscopy and positron emission tomography (PET) scanning machines. (See "Taking the Cake.") Its radiotherapies-four brachytherapies or "seed" implants for cancer treatment and pain palliation-capture 50 percent of the worldwide radiotherapy market. Its MRI contrast agent Omniscan (gadodiamide) is second only to Schering AG's Magnevist (gadopentate).

AH's global 2001 sales increased 13 percent from 2000, reaching $1.35 billion. The company's best-selling product is Omnipaque (iohexol), its x-ray agent in use for more than 20 years and considered the world's gold standard, with global sales of $324 million. Visipaque (iodixanol), another x-ray agent, has global sales of $117 million, a 28 percent increase from 2000. Those nonionic contrast agents, which are believed to cause fewer adverse drug reactions compared with other products, are one reason for the company's growth.

Taking the Cake

Its second largest selling product, Myoview (technetium Tc-99 m tetrofosmin), is a radiopharmaceutical imaging agent with $161 million in global sales. Up 27 percent from 2000, the product is propelled by the ever-increasing rates of cardiovascular disease and patient demand for screening, and AH expects that double-digit growth to continue. Omniscan reached $124 million in worldwide sales in 2001, an increase of 20 percent since 2000. The full portfolio of brachyherapy seeds achieved sales of $86 million in 2001, up 13 percent. Although no numbers were available for DaTSCAN and Neospect (technetium Tc-99m depreotide), two recently launched radiopharmaceutical imaging products, the company says they were "well received" by their respective markets.

Nevertheless, AH's products are not the only things that make its story compelling. Equally important is how it leveraged the years spent as a quiet industry insider to make the partnerships that will move the needle on genomics.

"The company's vision has changed. We now believe, perhaps more than we did five years ago, that the 21st century is all about diagnostics," says Padfield. He supports that vision by pointing to elements of the changing healthcare landscape that will drive growth of AH's products:

Aging population. Padfield notes that in ten years, 20 percent of the population of Western Europe, the United States, and Japan will be over the age of 65. Those numbers are poised to overwhelm current systems, with more people needing care and fewer people paying for it. Keeping patients out of the hospital represents the greatest cost-saving measure, while simultaneously improving patient outcomes. Padfield believes that improved diagnostic testing can do its part by allowing physicians to intervene in illnesses earlier, keeping patients healthier longer and reducing hospitalizations.

He also believes that, through increased use of the internet for healthcare education, people will insist on early intervention to protect their quality of life. He predicts that US baby boomers will be the first to form a new class of patients, the "symptomless ill," because they will be prepared to pay for better lives. The onus will be on pharma companies to discover and develop the products that keep them healthy.

Background on John Padfield

"Patients will become AH's customers much more than they are now," explains Padfield. "I can't use the word 'inconceivable' regarding Viagra (sildenafil), but 20 years ago, who would have imagined that we would be dealing with such sensitive issues? In 20 years, the world will be different again and it's our job to hold the crystal ball, see what the trends will be, and design products to meet those needs. We're all going to die at some point. The death rate is still one per person. It's only a question of when and how and whether we can improve patients' quality of life in the process."

Even with prevention, the graying of the population will drive product sales. According to the US Census Bureau, those age 45 and older require three to four times as many internal examinations as younger people. Currently, 35 million of "visually enhanced" procedures are done each year; by 2006 that number is predicted to increase to 50 million.

Technology advancements. Hardware companies have invested in replacing traditional CT scanners with high throughput multi-slice CT scanners that take "salami slice" pictures of the body in three or four seconds, replacing slower machines that take only a single picture at a time. That trend is expected to continue, enabling hospitals to meet increased demand for scanning. The annual growth rate for multi-slice machines is predicted to be 48 percent during the next five years, according to AH. That demand should propel growth of CT visualization agents, such as Omnipaque, Visipaque, and new products in development. (See "Down the Pike.")

Down the Pike

But because the machines run very fast, contrast products will be needed in greater quantity for most procedures to ensure the best possible image, as evidenced by an October 2001 study published in the American Journal of Roentgenology. A hospital upgraded to a multi-slice machine in one room after running single-slice CT machines in two rooms for one year. When compared with the control group, the number of scans conducted on the multi-slice machine increased by 50 percent, and the use of contrast products increased 70 percent.

New medical devices. Stenting, the procedure by which a thin, stainless steel mesh tube is inserted into a clogged artery, is possible because of arterial

visualization agents such as Visipaque. Currently, physicians conduct about 100,000 such procedures each year, but the compelling decrease in patient trauma, rate of restenosis-or reclogging-of the arteries, and faster recovery associated with interventional cardiology compared with surgery have analysts predicting that the number will more than triple to 350,000 by 2005.

From Modality to Disease

Jean-Michel Cosséry, Pharm D, PhD, MBA, executive vice-president, product strategy, joined AH in November 2001 and helped shift the company's approcach from an imaging modality to a disease-focused one. That move helped integrate its R&D and marketing departments, which now more closely mirror traditional pharma companies' therapeutic franchise models.

"When R&D scientists work with Cosséry's product strategy and marketing people, they understand the disease, the unmet diagnostic needs, where therapy monitoring is going, and the product needs," says William Clarke."That gives them clear marching orders. That doesn't sound revolutionary to some of my Big Pharma colleagues-but it really is revolutionary in the diagnostics business."

The approach offers more flexibility in diagnosis, taking into account patients' medical histories as well as physicians' differing approaches, which often varies by region. It also fits AH's raison d'etre, which is to enable physicians to perform the least invasive procedure possible.

"If a patient comes in with chest pain, the physician can use a radiopharmaceutical like Myoview to assess myocardial perfusion [blood flow] and/or an ultrasound product like Optison to see the functioning and border delineation of the heart wall," says Padfield. "If there is a problem in the heart wall, the physician may conduct a cardiac catheterization, inject the patient with the x-ray diagnostic Visipaque, and see whether the narrowing of a particular blood vessel is causing the lack of blood flow to the heart. Then, if the physician decides to do an angioplasty and put a stent in, they can do so using Visipaque to guide the process. In that way, AH provides products from the least invasive to the most invasive for physicians for every stage of heart disease."

That principle-doing the most for patients by doing the least to them-is also the basis of the company's line of brachytherapies: OncoSeed (iodine-125), TheraSeed (palladium-103), EchoSeed (iodine-125), and a method of implanting the therapeutic "seeds" more precisely, Rapid Strand (a rigid, absorbable, permanent implant device). The seeds, each about the size of an uncooked grain of rice, are implanted into tumors using a minimally invasive outpatient procedure. The seeds give off localized doses of radiation without harming healthy tissue, compelling physicians to use it for a wide variety of cancers.

The procedure offers substantial benefits over other cancer treatments, such as radical prostatectomies and external beam radiation for prostate cancer. Implantation takes about an hour, with three days' home rest, compared with a one- to four-hour radical prostatectomy, three-day hospital stay, and three to eight weeks of recovery time. Seed implant therapy is also a one-time treatment, compared with external beam radiation that is administered five days a week for four to six weeks. A decrease in side effects such as erectile dysfunction and incontinence, and reduced hospital costs are other implantation benefits.

Media coverage of former New York mayor Rudolph Giuliani's fight against prostate cancer and his subsequent participation in PROstate Health, a public relations initiative aiming to raise prostate cancer awareness, highlighted use of TheraSeed, which AH co-markets with Theragenics. Although the publicity helped get the word out about the product, TheraSeed's success brought increased pricing pressure from the resulting entry of multiple competitors into that market, according to Credit Suisse First Boston.

Its analysts also believe that the small number of seeds used per procedure contributes to the weakness of the brachytherapy market. Yet, the company is optimistic that the European market, among others, holds substantial growth opportunities for seed implant therapy because it is not well known or widely available there. As awareness grows, analysts also expect demand to grow. That even includes Japan, which currently has no approved seed products. Although the Japanese population suffers less from prostate cancer than other populations, the incidence is on the increase and seed products are expected to soon be available in that market.

Predict and Prevent

Although the idea of "predict and prevent" is familiar, AH's future ability to bridge the phenotype and genotype of disease-the physical symptoms and the genetic code that determines what causes them, respectively-may help usher in the much heralded age of personalized medicine.

Although Padfield says the promise of predict and prevent won't be entirely fulfilled for another 20 years, or until scientists know what happens before symptoms appear and how to use that information therapeutically, companies are already taking steps along the way.

The following drivers for the predict and prevent paradigm also ensure that AH will have a major seat at the table:

Less trial and error. Today's "one size fits all" approach to developing and prescribing products sometimes induces the desired effect in only one out of three people. Predictive tests using improved diagnostics equipment and agents will guide physicians' prescribing choices, ensuring efficacy for targeted populations and decreasing adverse drug reactions, currently a leading cause of death in the United States. To that end, FDA has already approved the first therapy targeting a specific gene expression shown to play a role in the development of breast cancer, Genentech's Herceptin (trastuzumab).

"One of my colleagues says that a clinical diagnosis used to be, 'I've heard you. Try this for two weeks. If it doesn't work, come back,'" says Padfield. "There is still too much of that, but the more diagnostics we can find and use, the more guesswork we can eliminate."

More effective, less costly, and safer clinical trials. It is reasonable to expect that, in the future, companies will screen clinical trial patients based on their genetic profile. Genetic biomarkers will play greater roles in determining patient selection and trials' clinical endpoints. In moving away from symptomatology and toward more concrete biological targets, trials may become more predictable, requiring less time and money, and resulting in fewer patient dropouts. Patients and patient groups are also expected to pressure those running clinical studies for diagnostic pretesting to safeguard against deadly side effects. (See "Post Genomics Drug Development, Is Pharma Ready?" PE, March 2002.)

More targeted marketing. Instead of driving sales of "blockbuster" drugs through a widely cast promotional net, marketing departments will increase their ROI through extremely targeted promotions. Targeted marketing may also bring disease management programs to a new level by capturing the market early, providing treatment, and being able to ensure outcomes because patients are preselected.

Cost-containment. To control costs and improve outcomes, third-party payers of the future may demand confirmed diagnoses before approving reimbursement for treatments. Although pharma costs may rise, indirect healthcare costs, such as emergency room visits, may shrink in response to greater patient awareness and treatment of disease through diagnostic testing.

No Longer an Ugly Word

"Drug companies need to welcome diagnostics as opposed to feeling they're a threat," says Padfield. "They will realize that they cannot get their products past regulators and payers unless they can demonstrate that the right patient is receiving the right drug at the right time. That's what we're about, and we'll work together more and more."

To make that a reality, AH established Imanet, a global network of imaging research centers, to serve as an interaction hub linking itself with hardware, pharma, and biotech companies. With access to radiopharmaceutical imaging, primarily through PET but also including spectroscopy scanners, AH stands ready to create intellectual property for all involved.

PET: Key to the Next Generation

AH taps Imanet's worldwide resources to help pharma companies better understand how its products work through images showing their effects in vivo. By screening molecules early in the development cycle and visualizing products' success in targeted cells, tissues, or chemicals, pharma can expedite their R&D process. (See "PET: Key to the Next Generation,")

"Imanet's a research tool that is used to help pharma identify whether a particular drug is appropriate for use in a clinical population and to determine variations in patient responses," says Padfield. "If they think a product targets a particular site and it doesn't, then obviously that patient will not benefit from it. It lets failures happen preclinically and not in phase III, when it is more expensive in cash terms and very expensive in stock market terms." AH hopes Imanet will lead to the development of specifically paired diagnostic and therapeutic products for itself and pharma company clients. Product bundling will allow companies to charge the highest price possible because the diagnostic will prove that the drugs are the most effective available. It will also allow physicians to diagnose more confidently. (See "Clinician Confidence,")

Clinician Confidence

Barring that development, the partnership gives AH access to a host of molecules that may have failed to be therapeutic but are excellent imaging agents because of their targeting precision.

"Having access to those highly specific agents with the horsepower of the pharma company that designed it, and not having to do primary target identification and validation, is a good deal," says Clarke. "We do it and are good at it, but not having to feed our entire pipeline through that is super."

AH's recent deal with Pfizer touches all of those points: Pfizer funds the company's research into ways to diagnose individuals' responses to particular medicines, and AH owns the rights to develop and commercialize diagnostics resulting from that research, even if Pfizer decides not to commercialize any therapeutics. The deal marks a milestone -a leading diagnostic company is working with a leading therapeutic company.

Imanet offers AH a spectacular vantage point from which to look inside pharma, according to Clarke. "We see the pharma business identifying an important mechanism of action and everybody running to get a therapeutic target. We can develop one imaging agent to cover all those companies' molecules, if they all make it to market. The pushback is, 'What is the likelihood of Company X's molecule making it to market?' Less than ten percent, but if we know eight of the top 50 companies are working on it, it's a good chance one or two will get approved. And we'll have an imaging agent ready that will let physicians know what patients are appropriate for that treatment."

Questions Abound

Amersham Health's vision for healthcare, a future in which people won't need to get really sick before they can get well, is fraught with uncertainties. Despite the company's 20-year plan, it remains to be seen if contrast agents will continue to play a role in healthcare or if advances in hardware technology will eclipse that need. To answer those questions, AH leans heavily on its other half, Amersham Biosciences. But its challenge is to break down the differences between the two groups, and bring them together as one company.

If diagnostic products are necessary for the near future, AH will have to work with industry and regulatory authorities in deciding who will be diagnosed, and when and how, and then what to do with the information. It is still unclear whether pharma companies will develop medications that could eradicate genetic diseases before or after they are expressed. The question remains: Is knowledge really power if a predisposed patient has no course of action against the disease? To help patients decide if they want to be scanned, genetic counselors and centers would have to be available on a wider scale.

And, if advanced diagnostic testing is available to all, who decides who gets screened? Even if it begins with high-risk patients, it costs too much to diagnose all those individuals. Therefore, various point-of-care diagnostics will be needed, such as cancer and cardiovascular disease testing kits, which doctors can use during routine physicals or patients can use at home.

Another challenge is finessing data into knowledge, or improving bioinformatics. If, in fact, one day people will have a detailed map of their own genome, where will that information be kept? Perhaps everyone will have a computer chip implanted that contains a detailed map of their individual genome and can be scanned by any hospital in the world. Although that may seem far-fetched, the possibility is closer now than ever before. According to news reports, members of one Floridian family have chips implanted in their arms detailing their medical histories.

Padfield also sees a need for major improvements in ultrasound technology on behalf of all involved parties, including hardware, diagnostic, and interpretive software companies, because it enables the least invasive imaging possible. For its part, AH is developing Sonazoid (lipid stabilized suspension of perfluorobutane microbubbles), an ultrasound agent targeted for the liver.

"Other products will come to the market from some of our competitors this year," says Padfield. "The more that people talk about ultrasound as an alternative to MRI or CT, the more it might come into greater use because, with products like Optison, ultrasound in cardiology will expand dramatically. The industry has the biggest challenge in that area because it is new. Maybe it will take 10 or 15 years to introduce ultrasound. But as part of our portfolio, we'll keep plugging away and do the best we can."

Finally, the company must show managed care organizations the value that advanced diagnostic testing will bring to their cost-containment and improved outcomes business model. That seems inevitable, but it could take a long time. After all, it took 19 years to get PET scans reimbursed.

The deciphering of the human genome in June 2000 intensified the spotlight on Amersham. Although the company has thus far blossomed under the scrutiny, how it handles those issues and the success of its pioneering efforts to bridge diagnostics with pharma through meaningful partnerships will determine its place in the emerging new world of healthcare.

Tomorrow's Solutions for Today's Problems: Amersham Health works with a New York physician to extend a helping hand.

With a unique approach to imaging, Amersham Health's investigational diagnostic agent, which it gained with the acquisition of Magnetic Imaging Technologies, has the potential to revolutionize treatment of chronic obstructive pulmonary disease and other respiratory disorders. By using hyperpolarized helium instead of oxygen, MRI images depict the exact pathways of gas in the lungs, which was previously impossible. Currently in Phase II trials, the technology improves the ratio of imaged helium in the lungs from one in 3,000 to 1,500 in 3,000.

Georgeann McGuinness, MD, submitted a proposal to the National Institutes of Health to image the lungs of New York City firefighters who were at Ground Zero on September 11, using Amersham Health's helispin agent, which is still under development.

Georgeann McGuinness, MD, New York University School of Medicine associate professor of radiology, saw the immediate application of helispin in diagnosing inhalation injury in many of the rescue workers who were at the site of the World Trade Center on September 11. She recently submitted a proposal to the National Institutes of Health to conduct a five-year study of 200 New York City firefighters. The study, if approved, will attempt to gauge the impact of that day on their health.

McGuinness: We have been performing computed tomography scans on a large number of World Trade Center-exposed firefighters, through a medical monitoring program jointly supported by the Fire Department of New York, the Bureau of Health Services, and the Centers for Disease Control, among others. The CT scans can give us structural information about lung injury, but this data does not provide us with functional or physiologic information, including evidence of reactive airway disease. Because the site of injury is deep in the lungs where the particle matter was inhaled, the airways involved are peripheral (small), beyond the capabilities of even high resolution CT, and correspond to a region in which lung injury is usually not detected by routine pulmonary function tests.

The New York firefighters are an interesting study cohort: They all had a unique, severe inhalational exposure on September 11. Because of mandatory medical monitoring within the fire department we have access to data, including pulmonary function tests, on the patients before 9/11.

And finally, there is the "healthy worker effect," which eliminates the confounding problems of preexisting diseases, because firefighters must be healthy to be on active duty. It is a perfect project to apply the new imaging technique to, and we may have the opportunity to provide valuable clinical insights into the lung injuries sustained by those firefighters during that tragic event.

In the past, MRI could not be utilized for lung imaging. Now, using a gas other than oxygen in the lungs allows us to gain valuable insight into lung morphology and function. Helispin can show how well the gas is delivered to specific areas of the lungs, the diffusion coefficient indicates whether air spaces and airways are altered in their dimensions; and we can visualize dynamic patterns of gas flow within the airways. We intend to compare this data with CT images and pulmonary function tests, but we already recognize that those tests are not terribly sensitive to the type of small airway disease that we suspect the firefighters have.

The subjects, many of whom are currently symptomatic, are potentially at risk for developing chronic lung diseases, and the available tests are insensitive to this type of lung injury. Even those firefighters without significant symptoms now are at risk for developing disease in the future. We wonder, when we look at the data over the five year duration of the project, if we'll pick up markers that indicate a predisposition for the development of chronic disease."

The long-term effects of breathing the air rising from the debris of the World Trade Center are still under debate, with medical experts disagreeing on its seriousness. The so-called ``World Trade Center cough'' developed by rescue workers and others at the site is characterized by various symptoms including shortness of breath and wheezing.

However, medical experts are still questioning the long-term side effects of that day. McGuninness' efforts, among others, aim to help bridge today's problems with tomorrow's solutions by using advanced imaging diagnostics.

Questioning the Gold Standard

William Clarke, MD, MSc, executive vice-president of research and development for Amersham and a practicing physician for more than 20 years, thinks it's critically important for regulators to reexamine some of the old gold standards and see if they are still applicable in light of new products, with completely novel mechanisms of action. Clarke, whose senior R&D staff will be speaking at the Parkinson's Action Network's upcoming meeting, believes that patients shouldn't have to wait for new diagnostics while investigators and companies perform longitudinal studies on chronic diseases.

William Clarke, MD, MSc

Clarke: The era of molecular imaging and in vivo in-patient diagnostics is ready to happen. The question is, how will we work together to make it happen as soon as possible?

Molecular imaging and molecular in vivo diagnostics are beginning to present the regulators with products that are so much better than the existing gold standards, and they are really struggling with it. Currently, regulators reference information for a new diagnostic against clinical gold standard diagnostics. In the days of registering new x-ray and MRI products, that was quite straightforward. Now, molecular diagnostics can diagnose disease at an extremely early stage in a way that cannot be determined by any other process.

The only way to determine the sensitivity and specificity of the diagnostic is to confirm the diagnosis by following patients around for years. As an example, molecular diagnosis of early stage Alzheimer's disease appears to be on the horizon. But since the confirmation of a diagnosis of Alzheimer's disease is at autopsy, current clinical trials may take as long as a decade to prove the efficacy of the new diagnostics. That is and should be unacceptable to patients, families, regulators, and the diagnostic industry. Together, we must all work to find a new and better way to determine the clinical utility of diagnostics so that patients and physicians can access those exciting and potentially valuable new tools in a matter of a few years versus decades. However, that problem is neither new nor insurmountable.

The industry faced a similar issue in the mid 1980s when presented with the new antiretrovirals for HIV/AIDS. Initially, the regulators told the companies to conduct two- to three-year trials and look for clinical outcomes such as progression of AIDS or even death. But physicians and AIDS activists rightly said that wasn't acceptable. Working together, physicians, AIDS activists, the regulators-and the FDA was notable for its forward-looking approach-and pharmaceutical companies were able to design new and highly accurate ways to predict the safety and efficacy of new AIDS drugs. The result of that joint effort was a revolution in AIDS therapy development and in patient care. There must be a way that a similar group can come together to bring a revolution in molecular diagnostics.

Regulators, medical professionals, and patient communities need to have a joint debate about the risk/benefit ratio in diagnosing diseases earlier. Isn't it better to diagnose thousands and thousands of patients with the disease, and start them on treatment, than to wait ten years and find out that DaTSCAN is 94 percent rather than 97 percent sensitive? The same problem is happening with Alzheimer's disease. There are ways to diagnose the disease early, but we can't conduct a 12-year clinical trial. And the Alzheimer's Association (AA) doesn't want that either because it's not much use to patients or to the pharma industry to design clinical trials that will take 10-12 years, at which time patients may be dead.

What we hope to do with AA and others is to help them understand the problem: Most people focus on therapeutics, but diagnostics are important in finding patients and getting them on the right medicine. Yet information about diagnostics is not available. But not because regulators don't care about patients. They do. It is just a new era, and we need to find a better way to diagnose patients. Consider what it means to misdiagnose only one person out of 100 with a molecular diagnostic agent, when right now we know we misdiagnose one out of four with standard tests.

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