Astonishingly, children still face similar risks today. The vast majority of
drugs have never been tested on children, forcing doctors to prescribe them “off
label”— outside the conditions for which they were licensed. They have to
gamble on a child being able to cope with the dosage they prescribe. This also
means that liability for the outcome rests with them or their health authority,
rather than the drugs company.

“Every paediatrician and GP caring for children faces this problem on a daily
basis,” says Vas Novelli, a consultant in paediatric infectious diseases at
Great Ormond Street Hospital in London. “Each is expected to weigh up the pros
and cons of using an unlicensed medication, knowing full well that they are
taking on the responsibility themselves for any major problems that may
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“Recent advances in biomedical research have not been translated into
advances in child health,” says Tim Westmoreland, a Washington lobbyist working
with the Elizabeth Glaser Pediatric Aids Foundation in Santa Monica. “For years,
doctors and parents have been put in the untenable position of [either] ignoring
drugs that are effective in adults or exposing children to drugs of unknown
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In 1997 in Britain, a House of Commons health committee on the needs of young
people expressed astonishment at this situation. Since then, however, nothing
has been done to remedy it. “The present lack of resources and capacity of the
workforce to improve knowledge and practice of paediatric drugs is nothing short
of a national disgrace,” says Al Aynsley-Green, the director of clinical
research and development at Great Ormond Street.

In the US, an estimated 80 per cent of prescription drugs are not licensed
for use in children, according to a 1996 report in Pediatrics (vol 98,
p 18). And the National Institute of Child Health and Human Development in
Bethesda, Maryland, estimates that only 5 of the 80 drugs most frequently used
in infants are licensed for paediatric use. However, the situation is set to
change with the Food and Drug Administration’s 1997 Modernisation Act, which
comes into force on 1 April this year. The act will force drugs companies to
provide the FDA with information on the paediatric use of any medicine that may
offer children better treatment than existing therapies, or will be widely used
by children.

Life-threatening

The legislation is long overdue, and doctors in Europe are hoping it will
encourage similar action there. On both sides of the Atlantic, there has been a
string of tragedies resulting from giving children pharmaceuticals that have not
been tested on them. In the 1980s, a drug called verapamil was widely used for
the treatment of certain heart conditions in children. The drug was approved by
the FDA after safety and efficacy tests in adults only. Between 1983 and 1987,
reports emerged of life-threatening adverse reactions, including heart attacks,
that required resuscitation. The drug is no longer recommended for use in
children.

More recently, adverse effects have been reported in children taking
cisapride, which helps gut contractions and is given every year to thousands of
young children who regurgitate their food. Some children who were given
unsuitably high doses suffered dangerous heart problems. The manufacturer now
plans to test the drug in children.

“In many cases, we have no real idea of the side effects different drugs
produce in children,” says Richard Cooke, director of the research unit at the
Royal College of Paediatrics and Child Health in London. “If randomised control
trials have not been performed, it is impossible to tell whether symptoms are
part of the patient’s condition or an effect of the drug.”

If a drug is not licensed for children, a doctor will often estimate a
suitable dose by extrapolating according to body weight from the recommended
adult dose. But children are not simply miniature adults—they react to
chemicals quite differently. For a start, the way the kidney excretes substances
changes in the first few years after birth, with different mechanisms maturing
at different times. Because of this, the proportion of a drug that stays in the
bloodstream depends on the age of a child.

The same applies to the liver, where enzyme systems that detoxify drugs
mature at different times. Thus the ability of the body to break down drugs also
varies with age. In addition, the proportion of water in the body changes
dramatically during the first two years of life, which affects the concentration
of a drug. Finally, children’s ability to respond to a drug may be different.
“The organ upon which it is supposed to work may be immature,” says Robert Ward,
a paediatric pharmacologist at the University of Utah in Salt Lake City.

Market forces

There are two main reasons why pharmaceuticals companies are reluctant to
test their drugs on children. First, there is not much money to be made.
Children consume small quantities of drugs and are a small proportion of the
market. Secondly, parents are generally reluctant to allow their children to
take part in clinical trials. For example, this month the Public Health
Laboratory Service in Britain announced that trials of a new children’s
meningitis vaccine had been delayed for up to a year because only half the 2000
volunteers needed had been recruited. In particular, they lacked recruits aged
three to four.

But in the US, drugs companies will soon have an incentive to overcome these
difficulties. As part of the new Act, for 493 drugs that the FDA considers a
priority, companies will be granted a six-month extension of their patents, in
exchange for comprehensive paediatric data. This could be lucrative: a 1993
report estimated that for an average drugs company, each year of exclusivity is
worth $100 million.

However, this deal will not help with drugs whose patents have expired and
that can now be produced by any company. Without market exclusivity, there would
be no financial incentive for the original patent holders to do trials in
children.

Despite the lack of legislation in Britain, there is momentum for change. The
Royal College of Paediatrics and Child Health is producing Medicines for
Children, the first formulary with data on drugs prescribed for children.
The dossier, due to be published in the spring, will provide information on how
drugs should be used and their common complications.

And last August, Aynsley-Green and four colleagues set up the British Forum
for Use of Medicine in Childhood. Their aim is to improve research, development
and training in paediatric pharmacology, and to make sure doctors get the
information they need. Such action is desperately needed to prevent children
being treated as what Harry Shirkey, former chairman of paediatrics at the
Children’s Hospital in Birmingham, Alabama, described 30 years ago as
“pharmaceutical orphans”.

Drugs companies in the US have been allowed to advertise prescription drugs
on television and radio since August 1997, and the hay fever campaign was among
the first to be shown. The companies have been free to promote their products in
consumer magazines since 1985.

Their European counterparts may only market their products directly to
doctors—advertising is restricted to medical journals. This ruling stems
largely from a 1992 European Commission regulation, and is backed by many in the
medical profession. They argue that it protects patients from unscrupulous drugs
companies. It is a position that many are finding hard to defend, especially
when over-the-counter medicines can be freely promoted.

European authorities are now coming under pressure to relax their ban. The
pharmaceuticals industry is believed to be preparing a major lobbying campaign.
And it is becoming easy for European consumers to read American publications
over the Internet. Patrick Deboyser, head of the pharmaceuticals unit in the
European Commission’s directorate responsible for the internal market, told a
meeting of the International Federation of Pharmaceutical Manufacturers
Associations this month that the ruling on advertising drugs may have to be
revisited “in the context of worldwide developments”.

Any such move would be highly controversial. Critics argue that advertising
is bound to give patients biased information. “Advertising is advocacy and that
means it only puts one side of the argument,” says Andrew Herxheimer, a retired
clinical pharmacologist and emeritus fellow of the Cochrane Centre in Oxford,
which disseminates data about healthcare to the public. “No balanced position is
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Advertising could disrupt the doctor-patient relationship, Herxheimer
warns. “It could make it more confrontational.” Nancy Dickey, president of the
American Medical Association, says this is just what has happened in the US.
“Valuable time is spent discussing why patients should or should not use a
particular drug, rather than concentrating on their medical problems.” In a
survey of 2000 American doctors published last month by IMS, a market research
group, 53 per cent of them reported an increase in the number of patients
requesting specific brands.

Some American doctors have welcomed advertising. They see it as a way of
countering efforts by private health providers to restrict patients to certain
products to save money. But the majority are worried about the impact it has had
on healthcare. In the IMS survey, 64 per cent wanted prescription advertising
limited or stopped.

The US government’s Food and Drug Administration (FDA) last month announced
plans for a random telephone survey of 1000 people nationwide to gauge the
effects of television advertising of drugs. “We’re going to ask if ads make
people more likely to talk to their physicians about problems, whether they
think they’re accurate, and whether they make them more likely to go
doctor-shopping,” says Brad Stone, an FDA spokesman. He says television
advertising could still be stopped if it turned out to be damaging.

Meanwhile, pharmaceuticals companies claim that promoting prescription
medicines helps to improve public health, by encouraging people who are ill to
see their doctor. A spokesman for Eli Lilly, which markets the antidepressant
Prozac, cites an article in The Journal of the American Medical
Association (vol 227, p 333) suggesting that only one depressed person in
ten receives adequate treatment.

Advertising directly to consumers can hugely increase profits for drugs
companies by targeting people with relatively mild symptoms who might not have
visited their doctor for help. Hay fever is one example. “It’s a huge market,”
says Gillian Shepherd, an allergist at New York Hospital’s Cornell Medical
Center. “In many cases there are no real differences between drugs a and b.”

Other conditions for which drugs are heavily promoted in the US are high
cholesterol, hypertension, osteoporosis, baldness, asthma, migraine and
arthritis. Scott-Levin, a US-based market research group specialising in
pharmaceuticals, estimates that last year American drugs companies spent
$1 billion in advertising such medicines
(see Figure). And it seems to
pay off. In August, the British-based drugs company Glaxo Wellcome announced a
sharp increase in US sales of several products it had promoted directly to
consumers by television advertising over the previous year. Sales of the group’s
antidepressant Wellbutrin, for example, had more than doubled.

Increased sales are one thing. Better medical care may be another, and
doctors in Europe warn that giving people unbalanced, superficial information
about medicines can be harmful. “The thing about advertising consumer products
such as washing machines and cars is that all things being equal people can make
up their own minds,” says Howard Stoate, a doctor who now sits as a Labour MP.
“It’s much more difficult to understand the exact pros and cons of an
antihypertensive drug. People don’t have a high enough level of medical
knowledge.” They may be persuaded to demand from their doctor a treatment they
do not fully understand.

A recent report by the King’s Fund, a London-based medical think-tank, does
not inspire confidence in the ability of pharmaceuticals companies to issue
balanced, useful information. A panel of 62 patients and 28 specialists surveyed
54 promotional leaflets, videos and audio tapes, mostly aimed at patients or
support groups. Just four were found to be of “adequate quality”. David Gilbert,
one of the authors of the report, says one of the main problems was the tendency
to promote the use of drugs rather than other types of therapy. “For companies
writing about depression, even if they didn’t mention brand names they
emphasised drug treatments over counselling and other psychological
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But the campaign to change the rules on advertising in Europe is gathering
pace. Richard Sykes, chairman of Glaxo Wellcome, told the Institute of Directors
in London earlier this year: “Patients . . . should always be as well informed
as possible. We need to get this debate out in the open.” Britain’s Patients
Association also says it would welcome patients becoming better informed. “We’re
supposed to have a partnership with doctors. Advertising encourages debate,
getting people to discuss what’s out there and whether it might be useful to
them,” says Joyce Robins, a member of the association’s council.

Even the attitude of Britain’s medical profession, which has traditionally
opposed consumer advertising, may be thawing. In March, an editorial in The
Lancet (vol 351, p 921) called for advertising of prescription-only drugs
to be allowed in Europe for a trial period. “Physicians should be strong enough
to cope with more informed patients, and the patient needs to realise that with
empowerment comes the opportunity to take a truly informed part in the
prescribing process,” it said.

Gilbert remains cautious. Promoting prescription drugs directly to consumers
may bring financial gains for companies, but there is no guarantee of health
benefits. And he warns that patients’ interests may not come first. The debate
could be decided by economics, not health.