‘Pragmatic’ Clinical Studies are the Way Forward

As a clinician it is near impossible to compare drugs based purely on EBM. Even the best meta-analysis is only a compilation of lesser studies that are, at best, equal comparisons of several treatment types. The real world use of a drug is almost always different, not least because your population in the clinical study may differ to the people you are treating. Hence the need for pragmatic studies.

Pragmatic clinical studies are essentially ‘real-world’ analyses of drugs and require a major shift in the way we approach pharmaceutical science.

The New York Times , in an occasional series called “The Evidence Gap,” examined the “growing movement” among researchers to conduct pragmatic clinical trials to gather evidence “that will fill some of the biggest gaps in medical science: What treatment is best for typical patients with complex symptoms?” According to the Times, “thousands of medical studies are completed every year,” but “most have relatively limited goals.” The Times reports that while such limited studies “can have value,” they “may no longer be enough, particularly when care has become so expensive and real evidence more crucial.”

A group of advocates is lobbying the US congress to provide funds for an Institute for Comparative Effectiveness Research, which would assess treatments and identify evidence gaps. The center also would initiate pragmatic studies.

Technologies to Watch through 2009

Sequencing

Pacific Biosciences is grabbing the attention of a large number of leaders in the genetics world with its assertion that the company will complete a high-quality sequence of the human genome in 15 minutes. Pacific Biosciences CTO Stephen Turner says that the company can complete that mission within the next five years. With it, a “raw” human sequence could be done in three minutes, reports Bio-IT World.

Vaccine Development

A new generation of virus-vectored vaccines is promising to take on a number of diseases like malaria. Instead of a traditional approach using weakened virus to produce antibodies that fight disease, researchers are adding the genetic code of molecules into the DNA of the virus. This ‘InVacc’ approach is believed to be more effective in supporting a strong immune response as it target CD4 cells specifically. It is also able to generate a significant response within days in animal models – days to weeks more quickly than your average vaccine.

Efficacy trials for the new approach may be mounted in Africa in three to four years, after researchers have had a chance to test a malaria vaccine. 

Personalized Medicine

Already a possibility, but not in common clinical practice. Now a few leading groups are using it, backed by impressive e-health systems.

From the NYTimes: The Marshfield Clinic, a large doctors’ group in Wisconsin, has shown that computerized records can indeed improve the quality and efficiency of medicine. Aided by their growing database, Marshfield’s physician-researchers are working on ambitious projects in personalized medicine that use genetic markers to tailor drug dosages. For example, the clinic recently began a clinical test on 250 patients that uses three gene markers to personalize their doses of warfarin.

Marshfield is also researching “predictive” medicine that combines genetics, family histories and lab tests to warn patients about looming health risks. It has a voluntary DNA database on nearly 20,000 people, whose health care information goes back 30 years on average — and the electronic record is the vehicle for collecting and conveying that information. The researchers are looking for patterns in family history, lifestyle, environmental factors, lab test results and selected genetic markers that might predict the onset of conditions like diabetes and Alzheimer’s disease years in advance.

2009 for Australian Pharma

Three key areas to watch the Australian Pharmaceutical industry in 2009:

1. PBS reform

The implementation of PBS reform was undoubtedly the story of 2008. The next 12 months are expected to show whether government promises in this area can be relied on. In particular, the trade off between paying less for listed items and generics and allowing more ‘headroom’ for novel therapeutics, is yet to be seen.

2. Global economic downturn effects

Resizing and restructuring is often managements response – though the exact purpose is not always clear. In this case several companies have been fingered by PharmaInFocus as likely to undergo these processes.

4. Specific M & A’s

I’m not into speculating about these, and they’re not guaranteed until the dotted line is signed as we have recently seen with Genentech, BHP and Quantas. For a good update check here.

Drugs to treat Autism?

The brain is the last frontier of medicine, and one that we are perhaps beginning to approach.

With the announcement that several trials are underway for drugs that treat rare, inherited conditions that are often linked to autism: Rett syndrome, fragile X, and tuberous sclerosis complex (TSC). 

Scientists hope that the new drugs, if successful in the current trials, will eventually help treat more common forms of autism, which affects about 1 in 200 children.

The mere concept that we might alter brain function is remarkable.

A group at MIT has corrected abnormal brain development and faulty memory and reduce seizures in a mouse model by decreasing mGluR5 activity by 50 percent.

E-Health Needed for Better Primary Care

The Australian Institute of Health and Welfare recently released a publication: Review and evaluation of Australian information about primary health care.

In it they have highlighted that accurate, reliable and timely information must be available to assess the quality, effectiveness and outcomes of services provided in general practice. These are currently not the norm.

Their findings are that existing data collections are limited. In particular:

• At the national level, ‘quality’ is currently only able to be assessed in specific circumstances and for particular health conditions (for example, tracking the annual cycle of care for diabetes).
• To enable thorough investigation of general practice care, data should:
  • be able to be analysed at the individual patient level
  • link each management action (such as a prescription, clinical procedure, pathology or imaging request) to a diagnosis or symptom pattern
  • be able to be linked to allow tracking of presenting problems and management actions over time and to examine patient outcomes.
  
  
  While there exist several info collections groups such as CONDUIT (Collaborative Network and Data Using IT), GPRN (the General Practice Research Network), the Australian Primary Care Collaboratives, ASPREN (the Australian Sentinel Practices Research Network) and the GP Census. These are only starting points. Features of each need to be adapted to a broader system.

Their Recommendations

• A minimum data set specification for GP–patient encounters should be defined, in consultation with all stakeholders, which builds on work already undertaken in this area.
• The options established as potential starting points for an electronic collection should be explored with all stakeholders to formulate an agreed approach for implementing collection of this minimum data set at the national level.
• Where existing collections provide useful data, they should continue to be supported during the transition period and, where appropriate, afterwards.

How they feel their findings relate to NEHTA’s work is not entirely clear from my brief perusal. But the data they provide is good market research for any company willing to enter the e-health arena.

Top Issues in Health for 2009

PricewaterhouseCoopers (PwC) has released a report on what it considers the top nine issues facing the healthcare industry in 2009.

While they are most relevant to the American market, many issues still apply to Australia. 

Listed below, one will notice two main themes arising from this report: 

1. Healthcare is becoming more expensive and therefore prevention, technology, and paying for performance or outcomes are coming to the fore.

2. Technology! More available genetic tests will have a huge impact on medicine and the power of the internet and associated technologies has not really been felt in healthcare as yet.

Here is a brief summary taken primarily from Fiercehealthcare:

1. The Economic Downturn Will Hit Healthcare 
Although the health industry historically has been less vulnerable to economic downturns than other industries, the disrupted economy will hit healthcare in 2009. Hospitals and other providers will experience an increase in bad debt and a drop in elective procedures. Improvement projects involving capital outlays for IT, facilities and equipment have been put on hold. Pharmaceutical and biotech companies have seen their valuations drop, which could further affect their access to raise additional capital. Health organizations that need to find new sources of capital will have to demonstrate that they’re improving their core businesses, improving efficiencies and delivering value.

2. The Underinsured Will Surpass the Uninsured as Healthcare’s Biggest Headache
The uninsured draw most of the attention, but the number ofunderinsured is growing even faster – an estimated 25 million adults qualify as underinsured, an increase of 60 percent since 2003. With some but not enough health insurance, the underinsured often can’t or won’t pay the high deductibles and co-pays for the services they need. In 2009, we could see more bad debts for hospitals, more cost-shifting to commercial plans and more patients delaying or foregoing care.
With growing unemployment, self-pay is becoming a major part of providers’ revenue cycle processes. Many hospitals have begun to prequalify patients. Some are using credit card-like swipe machines to verify eligibility and estimate insurance coverage. Not-for-profit hospitals must tread carefully, as they don’t want to further complicate the credit for uninsured and low-income patients. Business operations will likely look to technology and processes from the retail, banking and credit industries to manage self-pay patients and the underinsured.

3. Big Pharma turns to M&A to build the drug pipeline
With revenue from existing pharmaceuticals slowing down and the decrease of approved new drugs in the pipeline, Big Pharma is focusing on acquisitions of smaller biotech firms to reenergize the drug pipeline. Cash- rich pharmaceutical companies may be able to find bargains in the mergers and acquisition market as the financial markets continue to hit turbulence.

4. From Vaccines to Regulation, Prevention Is on the Rise 
Prevention will get a boost from drug makers, regulators and nonprofit benefactors, making vaccines one of the few bright spots for pharma sales. In addition, more state and local governments are regulating health-related behaviors, such as banning smoking in public areas and trans-fats in foods. Next up for consideration: Nutritional posting requirements for fast-food restaurants, limits on where cigarettes may be sold and fees for sugary sodas.

5. Genetic Testing Reaching a Price Point for the Masses 
The direct-to-consumer market for genetic testing may begin to take off in the year ahead as costs drop, enabling people to purchase a complete map of their DNA to identify markers for specific diseases such as Alzheimer’s. A federal ban on discriminating the use of genetic data could accelerate the use of these tests by the public. Research will focus on how genetics can affect pharmaceuticals and enable personalized medicine. The marketing of these tests bypasses traditional clinicians, raising questions about how the information will affect diagnosis and treatment. Regulations regarding genetics at a state and federal level will continue to develop.

6. The Internet and Social Networking Is a Powerful Health Extender
Technology will empower patients in new ways during 2009. The increased information and growing patient-to-patient interaction over social networking platforms and Web sites such as patientslikeme.com and americanwell.com are changing how healthcare is navigated and experienced by consumers, especially as electronic health records become more common.

7. Hospitals Must Perform to Get Paid
Medicare, Medicaid and insurance companies are increasingly basing reimbursement to hospitals on performance, and, despite resistance to it, pay for performance isn’t going away. In 2009, healthcare providers will have to get serious about not only improving performance but documenting it. The Centers for Medicare & Medicaid Services (CMS) has proposed adding a new index: the total performance score. It’s part of Medicare’s move to value-based purchasing. If Congress approves, CMS would replace the current quality reporting system with one in which Medicare withholds between 2 percent and 5 percent of its reimbursements to hospitals. They will need to focus on process improvements to improve safety and avoid unreimbursed medical errors, known as “never events.”

8. Payers and Employers to Give Incentives for Wellness Programs
More employers will give incentives to encourage responsible health behaviors and participation in wellness and disease management programs. Wellness programs don’t work if employees don’t participate, and most of them don’t, according to research by PricewaterhouseCoopers’ Health Research Institute which found that less than 15 percent of eligible individuals enrolled in wellness programs actually participate. However, they found that workers are two to four times more likely to enroll in wellness programs if they receive gift cards or other incentives. In 2009, health plans will begin to play a more active role in wellness program design, tools and support.

9. ICD-10 Will Require a Major Resource Investment
The conversion to a new International Classification of Disease code sets, known as ICD-10 will be a painful and costly process that health organizations will begin in 2009. The federal government has proposed an accelerated timetable for increasing the number of code sets used for billing and clinical classifications from 17,000 to 150,000. In addition to clinical process changes, the entire healthcare system – from quality of care, to medical records, to incentive salary systems, to reimbursement – will have to be adapted. The good news: When it’s done, providers and payers will have far more data on which to document diagnosis, decisions and reimbursement.

Direct to Consumer Pharma Marketing in Australia?

It seems we are maintaining our reputation as a conservative lot!  

Currently the EU, like Australia, bans advertising of prescription drugs. But this is to change as the European Commission recently proposed legislation that will let drug companies give consumers “objective and nonpromotional” information about their medicines. 

“Patients have become more independent (and) actively seek information” about drugs, the EU Commission said in a statement. “Consequently other sources of information are needed.”

It proposed that EU drugs makers be restricted in what they can say on packaging, leaflets and Web sites. They would be able to mention the price, the risks, verified data about the ailment the drug aims to relieve and the product’s environmental impact.

Importantly, manufacturers would not be able to promote a medicine or give information to people who haven’t asked for it.

Critics are concerned that it will ultimately encourage people away from cheaper generic medicines. The British consumer advocacy group Which! is predicting a US-style situation “where people demand specific branded drugs from the doctor when cheaper, equally effective drugs are available,” it said.

In Australia there are strict limits on what can be said on any drugs product information, with few differences being apparent that allow for marketing leverage. Pharmaceutical companies would welcome any move to relax this law as it would most likely allow them to maintain some brand leverage over generics when off patent.

What is far from clear, however, is whether the potential short term loss from lower generic uptake is offset by improvements in healthcare derived from the competition associated with the availability of more information. 

In Australia the mindset is still that consumers require doctors to make these decisions for them. One wonders how long this belief will last, and whether consumers will begin to force the governments hand through the increasing purchase of drugs from non-PBS sources.

Bush’s Parting Gift to Healthcare Workers with a Conscience

A Bush administration has finalized a law that gives health workers more room to refuse to participate in care they find morally objectionable. This law, and those that preceded is, are in stark contrast to recent laws passed in Victoria, Australia, that require healthcare employees to participate in abortion provision (PDF of proposed law).

Over the past three decades, Congress enacted several statutes to safeguard the freedom of health care providers to practice according to their conscience.  The new regulation will increase awareness of, and compliance with, these laws.
 
Specifically, the final rule:
 
– Clarifies that non-discrimination protections apply to institutional health care providers as well as to individual employees working for recipients of certain funds from the Department of Health and Human Services (HHS)
– Requires recipients of certain HHS funds to certify their compliance with laws protecting provider conscience rights; and
– Designates the HHS Office for Civil Rights as the entity to receive complaints of discrimination addressed by the existing statutes and the regulation.

But it’s not clear how long the rule will last once Barack Obama takes office.

Obama said prior to taking office that he was “committed to preserving the reproductive rights of women”. He will also review all 11th-hour regulations and will address them once he is president.”

The rule has the support of anti-abortion advocates but has raised the ire of organizations that favor abortion rights. It is set to take effect the day before President Bush vacates the White House.

IT Managed Elderly live Longer and Better

A Utah study using nurses tracking elderly patients with an e-health care package has found that morbidity and mortality can be easily and cost effectively reduced. This news comes as another study shows that many Medicare supported elderly receive sub-standard care in the US.

From the Portland Tribune: The patients, studied over three years by a team led by OHSU internist David Dorr, were actually enrolled at primary care clinics in Utah. Their average age was 76, and most had at least two chronic illnesses.

The study broke the 2,288 patients up into two groups – one group received standard health care and the second group received what the study calls Care Management Plus, which involved nurse managers using computerized records to carefully track patient conditions as well as needed tests and therapies such as medication changes.

The nurses and their computerized tracking appear to have extended the lives of patients in the second group, according to Dorr. The reason, he said, has to do with the fact that elderly people with chronic health conditions become complicated patients, and their care harder to coordinate.

About six out of 100 seniors receiving the higher level of monitoring died within a year of the program, compared to nine out of 100 of those receiving standard care. After two years, 13 out of 100 Care Management Plus patients died, compared to nearly 17 out of 100 in standard care.

Dorr said the study shows not only the health benefits of more coordinated care, but that electronic medical records and a higher level of patient monitoring also saves money in the long run.

Seniors with chronic illnesses receiving the higher level of monitoring had about four percent fewer hospitalizations after one year, and eight percent fewer hospitalizations after two years.

The study took place at 13 primary care clinics in Utah. The study estimates that decreased hospitalizations would yield a savings of between $17,000 and $70,000 per clinic.