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Press releases Saturday 08 September 2007

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(1) Screening family members could prevent 4 in 10 premature heart attacks
(2) Should terminally ill patients have the right to take partially tested drugs?
(3) Virological evidence cannot prove transmission in HIV criminal cases
(4) Developing World could suffer if drug safety is not properly assessed
(5) Concerns over effect of health reforms on public accountability

(1) Screening family members could prevent 4 in 10 premature heart attacks
(Families of patients with premature coronary heart disease: an obvious but neglected target for primary prevention)
http://www.bmj.com/cgi/full/335/7618/481

Screening and treating middle-aged adults with a family history of coronary heart disease could prevent more than 4 in 10 premature heart attacks, according to an article in this week's BMJ.

Researchers from the University of Glasgow looked at data from previous studies which show that immediate family members of patients with premature coronary heart disease (CHD) are at significantly increased risk of developing the disease.

Siblings are twice as likely to have a heart attack compared to the general population. Partners are also known to be at greater risk, due to shared risk factors in their lifestyle. The risk to family members increases further if more than one member of the immediate family has CHD.

Family history, the researchers say, can identify a large proportion of people at high overall risk of developing CHD. They point to one study which found that the 14% of families with a positive family history accounted for 48% of all CHD events and 72% of all premature deaths.

Using data from previous studies they estimate that in England and Scotland alone 7,369 premature heart attacks occur each year in people with a family history of premature heart attacks. Of those 6,485 might be preventable.

Once the risk of having a family member with CHD was taken into account they calculated that screening and treating middle aged adults with a family history could have prevented 42% of premature heart attacks and 8% of all heart attacks.

Many of the factors which increase the chances of developing CHD are modifiable, for example, smoking or having high blood pressure. So the researchers argue that family members would benefit from effective interventions to reduce these risks.

There have been attempts to identify high risk families via school, work or on-line questionnaires in the past, but the researchers believe "wide coverage could be achieved by identifying relatives whenever someone is admitted to hospital for premature heart attack. Furthermore they may be motivated by their relative's illness, thereby improving the attainment and maintenance of risk factor control."

Patients with CHD usually present acutely to A&E or are referred to an outpatient clinic. These patients, they say, could be flagged as requiring family counselling. They conclude immediate family are an obvious, but neglected group at which primary prevention should be targeted.

Contact:
Jill Pell, Greater Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland
Email: j.pell@clinmed.gla.ac.uk 

(2) Should terminally ill patients have the right to take partially tested drugs?
(Head to Head: Should terminally ill patients have the right to take drugs that pass phase I testing?)
http://www.bmj.com/cgi/full/335/7618/478
http://www.bmj.com/cgi/full/335/7618/479

As the United States considers allowing experimental drugs to be given to people at the end of life, two experts in this week's BMJ debate whether terminally ill patients should have the right to take drugs after initial safety (phase I) trials but before final approval.

Professor Emil Freireich at the University of Texas believes that patients should be allowed to judge the risks for themselves.

Around half a million people will die from cancer related causes in the Unites States this year, and many are given a hopeless prognosis, he writes. For most, the option of participating in clinical trials of new drugs that offer some promise helps them remain optimistic, but most cancer patients are unable to participate in these trials.

So why not offer these drugs to these patients on a compassionate basis, he asks?

He points to several objections including safety, interference with the development of the drug and with the clinical trial process. But he rejects these and argues that patients with advanced cancer and limited life expectancy should have the same privilege as all individuals in a free society – that is, to decide their own benefit : risk ratio.

It is tragic, he says, that regulatory bodies have created a circumstance where people have to live in an aura of hopelessness even though they have the will, the resources, and the ability to expose themselves to the risk of participating in investigational studies and to enjoy the potential for benefit.

The solution is legislation or judicial action to permit expanded access to experimental treatments for patients with limited life expectancy, he concludes.

But Dean Gesme, a medical oncologist in Minneapolis believes that use of drugs after phase I testing and outside clinical trials will damage both individuals and science.

He points out that more than 90% of drugs entering phase I trials are found unacceptable, and, of those approved, most provide incremental improvements rather than lifesaving treatments.

The allure of promising new drugs continues to engender false hope, he says, which may delay approval and erode the clinical trials system by substituting clinical enthusiasm and wishful thinking for evidence based medicine.

And who will bear the costs of open access to these partially tested drugs, he asks? Will government and others who are now seeking to minimise payments for marginally beneficial therapies be willing to pay for unproved drugs outside of formal clinical trials?

While doctors dream of the miracle cure for each of their terminally ill patients, we must accept the duty and responsibility to conform to both principles of evidence based medicine and the precepts of appropriate end of life care, he concludes.

Contacts:
Professor Emil Freireich, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Email: efreirei@mdanderson.org 
Dean Gesme, Community Medical Oncologist, Minnesota Oncology Hematology Professional Association, Minneapolis, USA
Email: dean.gesme@usoncology.com 

(3) Virological evidence cannot prove transmission in HIV criminal cases
(HIV phylogenetics)
http://www.bmj.com/cgi/full/335/7618/460

Virological evidence cannot prove transmission in HIV criminal cases, warn experts in this week's BMJ.

Viral phylogenetics provides a way of assessing the relations between viruses from different people. It allows us to estimate the probability that viruses from two particular people have a recent common origin. But there are serious limitations on what can and cannot be inferred using this technique.

The recent flurry of criminal cases brought against people in the United Kingdom accused of infecting their sexual partner(s) with HIV has resulted in several convictions, write Professor Deenan Pillay and colleagues in an editorial.

This has caused concern amongst health professionals and community groups about the detrimental effect such cases may have on disclosure of HIV infection and uptake of voluntary HIV testing.

In some cases, attempts have been made to present evidence on HIV viral sequence data in a similar way to DNA fingerprinting.

In our view, this analogy is seriously misleading, say the authors. When attempting to establish that transmission occurred between specific people, virological evidence should be used with caution and only in conjunction with the clinical and epidemiological evidence.

The greatest difficulty lies with the nature of the data, they write. Identifying a link between viruses from two people on its own says nothing about who infected whom. Other difficulties include the unlikelihood that all sexual contacts of all HIV infected people will be available for viral testing, co-infection with genetically diverse strains, and similarities in two virus genomes as a result of convergent or parallel evolution.

They advise caution when interpreting such data because the strength of any apparent linkage between viruses will never approach the degree of certainty generally expected of DNA data in a criminal court.

Phylogenetic evidence - together with clinical and epidemiological evidence regarding likely duration of infection, sexual history, and other relevant factors - can provide support for linkage between cases but cannot prove transmission, they say.

Despite the difficulty in determining linkage between specific individuals, phylogenetics can provide important new insights in investigations, they say. A recent example is a study of the timing of HIV-1 infections among Libyan children in hospital, which showed that most infections occurred before the arrival of the accused medical workers in the country.

It will be important that sufficient checks and balances are in place to allow full use of HIV surveillance data for public health benefit, without concern that the underlying purpose for identifying possible viral genetic linkage between people will be to support criminal proceedings, they conclude.

Contacts:
Deenan Pillay, Professor of Virology, University College London and Centre for Infections, Health Protection Agency, London, UK
Email: d.pillay@ucl.ac.uk 
Ruth Metcalfe, UCL Media Relations Office, London, UK
Email: r.metcalfe@ucl.ac.uk 

(4) Developing World could suffer if drug safety is not properly assessed
(Pharmacovigilance in developing countries)
http://www.bmj.com/cgi/full/335/7618/462

Millions of people could be put at risk because progress in getting the best medicines to the developing world is not being matched by an appropriate monitoring programme say the writers of an editorial in today's BMJ.

The developing world bears almost 90% of the planet's disease burden. More is being done to make sure the developing world has access to effective medicines. Drug companies are coming under greater pressure to remove the legal and financial barriers to access say the writers. While they acknowledge this is good they say progress is not being matched by the development of proper drug safety monitoring.

Drug safety monitoring, known as pharmacovigilance, was developed in the West after the thalidomide disaster in the 1960s. Around 10,000 babies were born with disabilities as a result of their mothers taking thalidomide as a remedy for morning sickness.

Now, data on any adverse effects associated with the use of a particular medicine are systematically collected and analysed identifying any potential problems. 96% of developed countries have pharmacovigilance systems in place compared to just over a quarter of countries in the developing world.

The writers argue that data compiled from countries in the West cannot simply be used to measure the effects of drugs new to the developing world. They say the incidence pattern and the severity of adverse reactions could differ greatly because of different genetic influences and the local environment.

The writers say there are a number of things that could and should be done.

In the short term they say information in these countries should be better pooled. So, for example, there should be more collaboration between the academic community, the pharmaceutical industry and individual governments in order to create a single database. They cite a successful collaboration between public health, drug access campaigns and a regional surveillance system called the East African Network for Monitoring Antimalarial Treatment and say more of these partnerships could be established.

They suggest the pharmaceutical industry needs to become more involved; effective public-private partnerships need to be established so there is collaboration beyond the obtainment of a drug license. Programmes should be developed which show the effectiveness of a drug in the real world. There are examples of this in Africa say the writers but they need to become the norm, not the exception.

In the long term every country should develop its own pharmacovigilance system, however the writers acknowledge this will be costly. At the moment countries in the developing world just don't have the resources, infrastructure and expertise. At the moment if it comes down to a choice between implementing a new vaccine programme and funding a pharmacovigilance system then the former will win.

So, they say, the WHO needs to take the lead in developing a novel funding model to support pharmacovigilance in the developing world. This could include, for example, developing exchange programmes to increase local expertise.

Contact:
Munir Pirmohamed, Department of Pharmacology, University of Liverpool, UK
Email: munirp@liv.ac.uk 

(5) Concerns over effect of health reforms on public accountability
(The market in primary care)
http://www.bmj.com/cgi/full/335/7618/475

Government reforms to primary care have shifted professional control away from general practitioners and financial control away from government, argue senior doctors in this week's BMJ.

The changes raise important questions about public accountability, they warn.

Since 2003 the UK government has created a market in primary care, write Professor Allyson Pollock and colleagues. This means that general practitioners are no longer contracted directly to the NHS and primary care services can now be purchased from corporate contractors using commercial contracts.

In March 2007 about 30 companies held commercial contracts to provide primary care services in England. These include general practitioner owned and operated companies; international healthcare corporations, including drug companies; and companies providing catering, cleaning, and laundry services under private hospital contracts.

But the authors warn that decisions about services have shifted from general practitioners to contractors. Commercial contracts, they say, have implications for service planning, public accountability, access to health care, and government control.

Market forces have also changed the legal basis of service provision and have replaced government regulation as the principal regulatory control. This allows alternative providers considerable freedom with respect to staff terms and conditions and the way in which care is provided.

Finally, they argue that the introduction of commercial contracts will see the jurisdiction for healthcare policy and law move away from national government to the European Union, even though the EU's mandate is trade and commerce and not public health.

The government has allowed more firms to provide NHS funded primary and community care because it believes that competition will improve the public health, write the authors. But nothing is yet known about the consequences for access, costs, quality, and accountability. It is surely time to evaluate the policy, they conclude.

Contact:
Allyson Pollock, Centre for International Public Health Policy, University of Edinburgh, Scotland, UK
Email: allyson.pollock@ ed.ac.uk 

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