Building bridges: A new dawn of collaboration for the pharmaceutical industry

Medical Tribune June 2009 P2

Pharmaceutical companies must branch out and forge new collaborations if they are to survive the global economic crisis, says Mr. Abhijit Ghosh, life sciences leader, PricewaterhouseCoopers Services LLP, Singapore.

The pharmaceutical industry is entering a challenging era of uncertainty. The global economic crisis has intensified the strain on a marketplace which was already struggling to come to terms with soaring costs, the drying up of drug pipelines, and the pricing pressures created by the emergence of generic medications. We predict that by 2020 the current business model will become unsustainable, and a new landscape will arise for companies, healthcare providers and patients alike.

Pharmaceutical companies must adapt quickly if they are to survive these challenges and emerge stronger in the new marketplace. The days of ‘blockbuster’ drugs are coming to an end, and companies can no longer rely on a strategy of making huge investments to single-handedly develop and market their most promising molecules. Public expectations, too, are changing: as patients become better informed they demand a more holistic approach to healthcare, shifting the balance away from universal, one-size-fits-all treatments and into the realms of prevention and personalized medicine. Moreover, by 2020, medicines will be paid for on the basis of results, not products, and companies will be forced into offering broader health management services to ensure that they achieve the best outcomes.

Few companies will be able to meet these daunting goals on their own. In an industry where ‘profiting alone’ has long been the mantra, it is now ‘profiting together’ that offers the key to survival.

We predict that pharmaceutical companies will join forces with a range of external organizations in future: from hospitals and academic centers to companies which offer physiotherapy, stress management, nutritional advice and health screening. Many of these collaborations will be unconventional, as an increasing number of non-pharmaceutical companies enter the arena. The technology sector in particular is one where partnerships with the pharmaceutical industry will be beneficial, as drug providers team up with manufacturers of portable devices and implants.

Two models are proposed for the strategy of collaboration. The first is the federated model, which would see a network of separate entities coming together with a common goal and a shared supporting infrastructure. Each partner could play to their strengths and expertise: for example, the pharmaceutical company could focus on drug development while other players worked on improving patient compliance and encouraging them to lose weight. One such example of federated collaboration is already underway in Spain, where Vodafone has joined forces with Aerotel Medical Systems, a device manufacturer, and Medcronic Salud, a telemedicine provider, with a view to providing wireless home monitoring services. Bringing clinics and hospitals into such partnerships in future could even provide medical companies with access to outcomes data, allowing them to monitor the long-term effects of treatment outside the clinical setting.

The second approach to collaboration is the fully diversified model, in which a pharmaceutical company expands to provide related products and services. This enables them to spread their risk away from reliance on blockbuster drugs and into other market areas. Johnson & Johnson, for example, has branched out from drugs into medical devices and diagnostics, and has recently begun building a web-based wellness and prevention platform. GlaxoSmithKline (GSK) and Novartis have both invested heavily in vaccines, while Roche is translating its expertise in molecular diagnostics into consumer products for measuring allergen levels indoors. These diversification approaches, however, require substantial investment, and may detract from the core business and create risks which might even alienate investors.

Besides the financial and commercial benefits of increased collaboration, there are also obvious public health implications, particularly as the global burden of chronic disease continues to rise. Research by the RAND corporation shows that the US alone could save some US$28 billion if all diabetes, asthma, pulmonary disease and congestive heart failure patients enrolled in disease management programs – not to mention the considerable economic benefits in terms of working days saved.

Pharmaceutical companies will need to make their own decisions on how to move forwards, depending on their individual circumstances. Some are already exploring collaborations which previously may have seemed unlikely. In April this year, for example, GSK and Pfizer announced the joint formation of a new firm for HIV drug development, with 11 existing products and a further 17 in the drug-discovery pipeline. It is hoped that this combined venture will offer a broad and sustainable approach, with potential for growth in future.

Some companies, however, will find it harder than others to survive the current economic crisis, and it is small biotech firms that may face the roughest ride. Those with one or two promising molecules in the pipeline will most likely need to collaborate with big companies for their development, or seek to sell their stake entirely and join the ever-growing number of mergers and acquisitions.

Despite the current crisis there is optimism in the industry: in a recent survey we found that CEOs of pharmaceutical companies were more confident about their prospects for growth than their peers in other industries. It remains to be seen how the landscape will evolve and whether this optimism will be justified, but it is clear that the industry cannot stand still. Profiting alone is no longer an option, and the sector must branch out into new partnerships if it is to continue to move forward.

New risk tool allows prediction of dementia in elderly

Medical Tribune June 2009 P3

David Brill

A new algorithm could help physicians to stratify elderly patients according to their risk of developing dementia.

The late-life dementia risk index was developed using data from 3,375 subjects with a mean age of 76. Just 4 percent of those classified as low risk developed dementia over 6 years, compared to 23 percent of moderate-risk and 56 percent of high-risk subjects.

"This new risk index … could be used to identify people at high risk for dementia for studies on new drugs or prevention methods,” said lead author Dr. Deborah Barnes, University of California, San Francisco, US. “The tool could also identify people who have no signs of dementia but should be monitored closely, allowing them to begin treatment as soon as possible." [Neurology 2009 May 13; Epub ahead of print]

Laughter: The best medicine for cardiovascular disease?

Medical Tribune June 2009 P3
David Brill

Watching comedy shows can improve cardiovascular risk factors, researchers have reported in the journal Psychosomatic Medicine.

The study of 18 healthy people found that arterial stiffness and central hemodynamics improved after watching a 30-minute section from the movie Naked Gun. Cortisol and von Willebrand factor levels also decreased with laughter, reported the team from Athens Medical School, Greece.

Watching stressful scenes, however, had the opposite effect: carotid-femoral pulse wave velocity increased after watching a 30-minute clip from Saving Private Ryan. Stressful viewing also lowered interleukin-6 levels, but did not affect fibrinogen or soluble CD40 ligand levels. [Psychosom Med 2009 Feb 27]

Gene variants point to East Asian health risks

Medical Tribune June 2009 P3
David Brill

Korean scientists have identified East Asian-specific gene variants which play a role in obesity, blood pressure, bone density and pulse rate.

The group, led by the National Institute of Health, Seoul, conducted the first large-scale genome-wide association study of an East Asian population. They analyzed 8,842 samples from Korean population-based cohorts.

Besides identifying novel East Asian gene variants, they also found that many genetic markers are shared with Europeans, including several which play a role in height, body mass index, type 2 diabetes, obesity, heart disease and osteoporosis. [Nat Genet 2009 May;41(5):527-34]

Alcohol ‘flush’ signals cancer risk in Asians

Medical Tribune June 2009 P4

David Brill

East Asians who ‘flush’ when drinking alcohol could be at increased risk of esophageal cancer if they do not drink responsibly, a recent study has warned.

The characteristic red cheeks and nausea are a well-recognized phenomenon, but few people are aware that the underlying enzyme deficiency also predisposes heavy drinkers to squamous cell esophageal carcinoma, say the researchers.

With some 36 percent of East Asians displaying the flush response, there is potential to save “a substantial number of lives” by counseling affected individuals against heavy drinking. [PLoS Med 2009 Mar 24;6(3):e50]

"Cancer of the esophagus is particularly deadly, with 5-year survival rates ranging from 12 to 31 percent throughout the world,” said lead researcher Dr. Philip Brooks, of the US National Institute on Alcohol Abuse and Alcoholism. “And we estimate that at least 540 million people have this alcohol-related increased risk for esophageal cancer.

"We hope that by raising awareness of this important public health problem, affected individuals who drink will reduce their cancer risk by limiting their alcohol consumption," he said.

Flushing is caused by a deficiency in aldehyde dehydrogenase 2 (ALDH2) – an enzyme which breaks down acetaldehyde, a carcinogenic by-product of ethanol metabolism. People with normal ALDH2 function can convert acetaldehyde safely into acetate, but in ALDH2-deficient individuals it accumulates in the body, leading to facial redness, nausea and tachycardia.

In people who are homozygous for the ALDH2-deficiency gene, the response to alcohol is so unpleasant that they cannot consume large quantities, and are thereby protected from the associated risk of esophageal cancer.

Heterozygotes, however, can develop tolerance to acetaldehyde and may become heavy drinkers. Studies from Japan and Taiwan have shown that ALDH2-deficient heterozygotes who drink heavily are over ten times as likely to develop esophageal cancer, [Jpn J Clin Oncol 2003 Mar;33(3):111-21; Int J Cancer 2008 Mar 15;122(6):1347-56]

Dr. Michael Wang, a radiation oncology consultant at the National Cancer Centre Singapore, agreed that the link between flushing and esophageal cancer is not likely to be common knowledge among doctors.

“From the article, it is fair to comment that there is a causative relation between deficiency of the gene and increased risk of esophageal cancer,” he said.

“However, there has been a lot of material published since the 1970s regarding this condition. This relationship may be confounded by smoking, which is also related to esophageal cancer. Before we say something drastic like ‘people who flush when drinking have a higher risk of contracting esophageal cancer,’ we should research all the previously published articles first.”
Wang added that all heavy alcohol drinkers should be counseled, since drinking also predisposes to other medical conditions and to drink-driving.

The study authors advise clinicians to determine whether East Asian patients are ALDH2 deficient by asking simple questions about their history of flushing when drinking alcohol. Identified flushers should then be advised of their cancer risk and encouraged to moderate their consumption, they say.

Fatty fish and fish oils could lower HF risk in men

Medical Tribune June 2009 P5
David Brill

Moderate consumption of fatty fish and marine omega-3 fatty acids may help to protect against heart failure (HF), a study of Swedish men has found.

Eating fatty fish once a week reduced the chances of developing HF over 6 years by 12 percent, while consuming around 0.3 grams a day of marine omega-3 fatty acids reduced the risk by 33 percent (adjusted hazard ratios 0.88, 95 percent CI 0.68 – 1.13; and 0.67, 05 percent CI 0.50 – 0.90).

The apparent protective effect did not grow stronger with increasing consumption, however. Eating more than moderate amounts, in fact, restored HF risk almost to that of men who did not consume any fatty fish or marine omega-3 fatty acids.

The researchers conducted food questionnaires in 39,367 men aged 45 to 75, and followed them up in inpatient and cause-of-death registries from 1998 to 2004. A total of 597 men developed HF in this time, 34 of whom died. [Eur Heart J 2009 Apr 21; Epub ahead of print]

“Our study shows that a moderate intake of fatty fish and marine omega-3 fatty acids is associated with lower rates of HF in men, but that the men did not gain a greater benefit by eating more of these foods,” said lead author Dr. Emily Levitan, a cardiology research fellow at Harvard Medical School, US.

“This study reinforces the current recommendations for moderate consumption of fatty fish. For example, the Swedish National Food Administration recommends consuming fish two to three times per week, with one of those portions being fatty fish. Similarly, the American Heart Association recommends eating fish, preferably fatty fish, twice a week,” she said.

Omega-3 fatty acids, which are found in fish oil, have been previously shown to reduce blood pressure, triglycerides and platelet aggregation, and to benefit heart rate and endothelial function. Consumption of fatty fish, such as salmon, herring and mackerel, has also been shown to confer cardiovascular benefits: one such study found that moderate consumption reduced the risk of coronary death by 36 percent and total mortality by 17 percent. [JAMA 2006 Oct 18;296(15):1885-99]

The reason for the U-shaped association between consumption and HF risk in the present study is unclear, said Levitan, although she speculated that men with poor health may be eating more fish in an attempt to improve their wellbeing.

“It will be important to replicate these findings in other populations, particularly those including women, as our study was conducted in men only,” she added.

Omega-3 fatty acids may also have a protective effect against age-related macular degeneration (AMD), a recent study of elderly Australians suggests. One serving of fish per week reduced AMD risk by 31 percent, with a similar magnitude observed for consumption of long-chain omega-3 polyunsaturated fatty acids. [Arch Ophthalmol 2009 May;127(5):656-65]

The OMEGA (Randomized trial of omega-3 fatty acids on top of modern therapy after acute myocardial infarction) trial, however, found that daily consumption of omega-3 fatty acids had no benefit for preventing sudden cardiac death after acute myocardial infarction, in a cohort of 3,851 patients with 1-year follow-up. The results were presented recently at the Annual Scientific Session of the American College of Cardiology.

End-of-life discussions reduce costs and relieve suffering

Medical Tribune June 2009 P7

David Brill

The decision to prolong life in advanced cancer patients presents an ethical, emotional, and financial challenge. Buying time can be costly, and a heavy legacy is often left for families and healthcare providers alike.

A new study suggests that physicians can play a major role in relieving this burden, simply by talking patients and families through their options and helping them to make plans in advance. Patients who had these end of life discussions received fewer aggressive interventions and had substantially lower medical costs, researchers found.

Economics aside, these discussions could also be in the patient’s best interests: the study found that high medical costs in the last week of life correlated to increased physical and psychological distress, and a worse quality of death. Moreover, survival was not significantly longer in patients who received aggressive therapies – raising questions as to whether the expense is justified.

Senior author Dr. Holly Prigerson said that patients ultimately have the right to choose, but that physicians can help to ensure that they make an informed decision.

“We’re not saying you should or you shouldn’t [prolong llfe], but you should at least realize what you’re buying with this more aggressive care. There is not improved quality of life,” she said.

“Whether they want to endure that pain is up to the patient to decide, but at least they should have the information to know that when they’re resuscitated, the likelihood that they’re going to survive an extra week really isn’t that much greater.”

Prigerson, director of the Center for Psychosocial Oncology and Palliative Care Research at the Dana-Farber Cancer Institute, Harvard Medical School, US, said that the study was born out of a belief among some oncologists that having end of life conversations would make patients “needlessly hopeless and depressed.” With data now showing that these discussions actually improve quality of life, she hopes that the study will bolster the confidence of physicians to address these “very difficult” subjects in future.

Singapore palliative care expert Dr. Cynthia Goh agreed that these conversations are important but stressed the need to approach them correctly. Physicians should listen to what patients and families want and guide them through their options, rather than pushing them towards a decision, she said.

“When talking about, for example, ‘do not resuscitate’ orders, the wrong way of doing things is to say: ‘do you want us to save your father or not?’” said Goh, director of the Lien Centre for Palliative Care at Duke-NUS Graduate Medical School, Singapore.

“What they’re talking about in this paper is a different kind of end of life conversation, which is certainly not initiated in the hospital corridor. It’s not about ‘do you want this or do you want that’ – really it’s a conversation to say what is important for the patient. People go bankrupt for this kind of treatment, so having the chance to reflect on whether it is likely to fulfill their life goals is a very good thing.”

Prigerson and colleagues interviewed advanced cancer patients from several US institutions, and followed them up until death. Of 603 patients, 188 (31.2 percent) reported having had an end of life conversation with a physician at baseline. [Arch Intern Med 2009; 169(5):480-8]

The mean cost of care for these patients was US$1041 (35.7 percent) lower than in those who did not have such conversations (P=0.002). Medical costs did not correlate to survival time (P=0.70) but were associated with worse quality of death, as assessed by caregivers and family members (P=0.006).

Another recent study led by Prigerson found that cancer patients who used religion to cope with the advent of death were more likely to receive intensive life-prolonging care. [JAMA 2009; 301(11):1140-7]

The explanation remains unclear but the effect appears to be driven by be a subset of patients who are not lifelong believers but rather turn to religion as death approaches, she said. Their new-found beliefs could therefore be a proxy for psychological distress, which manifests in a desire to remain alive for longer.

Goh, who is also honorary secretary of the Asia Pacific Hospice Palliative Care Network and co-chair of the newly formed Worldwide Palliative Care Alliance, said that the findings were very interesting but may not be applicable to Asian populations since the study patients were all American Christians. She added, however, that religion is an important factor in end of life decisions, and said that physicians should take these beliefs into account on a patient-by-patient basis.