[Ip-health] Le Monde Diplomatique: The hard sell (English translation, January 2015)

Thiru Balasubramaniam thiru at keionline.org
Wed Feb 11 02:58:07 PST 2015


>From research laboratory to doctor

The hard sell

Drug companies prioritise profit over patients, and they control their own
clinical trials, which do the same

by Quentin Ravelli

“I realised I was being spied on, and the drug company knew exactly what I
was prescribing,” said a doctor from a smart Parisian practice. “I was
naive. I’d never realised. A drug company rep said to me: ‘You don’t
prescribe much.’ And I thought — how would she know that?” Drug companies’
marketing departments coordinate such tactics, which shock many medics: the
big pharmaceutical firms go to great lengths to maintain or grow their
market share, and will change a drug’s indications to gain new business.

Pyostacine (“Pyo”) was long prescribed as an antibiotic for skin infections
and considered by some medics the best for the job. It is now widely used
to treat broncho-pulmonary and ear, nose and throat infections. This last
use has been criticised by many doctors and public health authorities, as
it may contribute to over-consumption of antibiotics and the wider problem
of antimicrobial resistance, a major public health issue responsible for
700,000 deaths a year (see ‘Antibiotics aren’t automatic’). Pyostacine is
made by Sanofi, the fourth largest pharmaceutical company in the world
(with a turnover of $40.3bn in 2013).

For four years, I followed the development of this drug, from the research
laboratories through the manufacturing plant to doctors’ consulting rooms,
to gain an understanding of the versatility of medical products (1). At
every stage, the product had a different name: the biologists talked about
Pristinae spiralis bacteria; the chemists referred to the pristinamycin
produced by the bacteria; sales reps told doctors about the benefits of
Pyo; and the factory workers nicknamed it “Pristina” or “the bug”. Over
this process, there was a shifting dynamic between the patient’s needs and
the company’s profits, and between the drug’s use value and its exchange
value (2). This increased the tension between employees and managers,
particularly strong in a company that was going through major
restructuring, a process in which employees had little say.

Sales and marketing

Sanofi’s marketing department is on the third floor of the company’s
offices, in a southern suburb of Paris. Members of this team have been
promoting Pyostacine for respiratory infections since the 1990s. They
increased sales for broncho-pulmonary infections over eight years by 112%
(compared to growth of just 32.6% for skin infections). This is the result
of commercial strategy, as the market for respiratory infections is by far
the larger. “It turned out to work really well against germs that infect
the bronchia, lungs and sinuses,” a company doctor said. “So that was the
direction we developed its recommended uses in.”

The people who work this commercial magic are the product managers, who
specialise in promoting a single drug or family of drugs. Celia Davos (3)
is product manager for Pyostacine. She describes herself as “very business
orientated”: “Your job [as a product manager] is to monitor your [drug’s]
performance, monitor your product, to see where it’s going compared to its
competitors, in the context of the market ... and to do everything you can
to maximise its turnover.” This role is central to the marketing
department, which is the heart of the company, and acts like a career
turntable. Employees may be appointed as product managers from various
departments and subsequently redeployed to other managerial, marketing, PR
and sales roles.

The product manager provides support materials to the drug reps who visit
doctors to get them to prescribe their products. For Pyostacine there is a
guide to help reps explain the product, using arguments set out by the
marketing team; a short synthesis of the key points; and extracts from the
medical journal Infectiologie, sponsored by Spilf, France’s professional
body for the study of infections, describing the latest clinical trial
successes for Pyostacine. The reps also carry Pyostacine-branded freebies:
plastic torches with tongue depressors to allow the doctor to examine a
patient’s throat, boxes of tissues for the consulting room, pens and USB
thumb drives.

Some doctors are of more interest to the drug companies than others. Those
deemed to have significant “prescribing potential” receive most attention.
To identify them, the companies use information from the health sector
economic interest group GERS (Groupement pour l’Elaboration et la
Réalisation de Statistiques), which collects sales data from wholesalers
and pharmacies, and Cegedim (Centre de Gestion, de Documentation,
d’Informatique et de Marketing), which collates data from doctors’
prescription software. There are informal information sources, too, such as
feedback collected by reps from pharmacists or other colleagues. Doctors
classified as “low prescribers of antibiotics”, even if fans of Pyostacine,
will be less aggressively targeted than “high prescribers of antibiotics
who are low prescribers of Pyostacine.”

Preferred doctors

Such strategies do not automatically translate into sales. That is where
the reps come in. In 2014 there were 16,000 in France, the majority of them
women. At six calls per day for 213 days a year, that is 20m annual
encounters with doctors. To maximise their effectiveness, the marketing
departments produce brochures outlining “typical profiles”: the “female
doctor who is a union member”, the “thrifty doctor”, etc, which are used in
training seminars to establish “loyalty pathways”. Reps learn that the
family doctor — 55 years old, with a large practice — is more “sensitive to
the humanist approach to the patient” than the scientific doctor “working
in the countryside”. The rep tries to increase doctors’ “elasticity”; the
more elastic the practitioner, the more receptive he is to the company’s

Doctors are increasingly critical of drug companies’ methods, and some
refuse to see reps; rep numbers have fallen in the past decade. This has
forced drug companies to find less blatant forms of lobbying, by targeting
“key opinion leaders” (KOLs), figures respected by other professionals.
Sanofi tries to influence heads of university faculties, because of their
role in training junior doctors.

When I was an intern at Sanofi, I had to come up with ways to persuade
faculty heads to allow the company’s reps into their lecture theatres. The
poor results of some schools of medicine were used as leverage. At one
school that had seen a sharp fall in the number of its students ranked in
the top 25% in the national competitive exams, Sanofi claimed this was
because of the personality of the dean, who would not allow reps to
distribute corporate brochures, posters and other publicity material.

At every level there are doubts, disagreements and contradictions. Some
reps, well versed in drug resistance, talk to doctors about all the
antibiotics available, not just the most profitable ones. They try to
establish relationships that are not solely commercial, and voice their
doubts. But such reps often find their jobs or their territory changed, or
are disciplined by management, all of which are difficult to oppose when
the threat of redundancy is in the air.

Production, a tough shift pattern

The factory where Pyostacine’s active ingredient is made is south of Rouen,
an area that is home to a number of industrial complexes including Total
and ASK Chemicals. At the Sanofi plant, which has been affected by
redundancies, some buildings have been replaced with grass. Production
units still functioning are linked by pipes that carry oxygen, purified
water, solvents and acids. When you enter these buildings for the first
time you are struck by the smell: agricultural byproducts (sugar beet
molasses) feed the fermenting bacteria.

Noise levels are high in the fermentation rooms; the long blades of dozens
of fermenters turn like propellers. The pristinamycin produced here will
later be sent to Spain for packing and then sold under the Pyostacine
brand. The workers say they find their jobs interesting and enjoy the
unpredictability of working with living organisms. But conditions are
tough: workers are on a shift pattern that divides them into five teams
working two days from 5am to noon, two days from noon to 8pm, then two more
from 8pm to 5am. Officially they are then entitled to four days off. But 11
times a year, they lose a day under a “catch-up” system (otherwise they
would end up working fewer than 35 hours in a given week) and have just
three days off, further abbreviated by the requirement to finish the cycle
late at night or return to work early in the morning. Workers never sleep
the same hours three nights running. “Your brain can’t get back into a
regular pattern of sleeping and waking,” said Etienne Warheit, who is in
his 34th year of this regime. “You feel permanently unable to do your job
properly. You do things three times because you’re scared of forgetting
something, or making a stupid mistake. You lose confidence in yourself.”

When exhausted workers ask to switch to day shifts, they are often told no
posts are available. The main objective is to maximise the profitability of
the machines, which run round the clock, and management falls back on
technical determinism, claiming that the biochemical rhythms of
fermentation and bacteria extraction make the pattern inevitable. This
“scientific” justification discourages any collective organisation. It’s
part of a “biotechnological” attitude: the factory comes to resemble a
laboratory according to the production director, or a “small or medium
business”, where workers have no reason to protest.

There is a huge gap between the company’s practices and its message —
“Health first” (the slogan at the factory entrance). But neutralising
protests, which make one HR employee feel they are “sitting on a powder
keg”, has become part of the company’s industrial strategy. By inviting
many workers to become technicians, the company has managed to convert
collective demands for better conditions into individual hopes of
promotion. From the late 1990s until 2005, the group management used the
threat of a factory sell-off to push through a restructuring plan and
redundancies. The factory has gone from “under threat” to “pilot site” for
the Sanofi group.

This turnaround — which did not change working conditions or salaries —
reflects the powerful industrial usefulness of bacteria. The “biotech boom”
may mark a general reorientation of industrial capitalism in the 21st
century towards biotechnologies: green (agriculture), white (industrial),
yellow (pollution treatment), blue (based on marine organisms) and red
(medicine). Markets are developing for all of these and the profit margins
are often enormous, which explains why the pharmaceutical industry has been
snapping up biotech firms. In April 2011 Sanofi acquired Genzyme for $20bn;
this US company specialises in biomedicine for multiple sclerosis and
cardio-vascular conditions. The appeal is that the new treatments are not
coming from classical chemistry but from the exploitation of living, often
genetically modified, materials, which allow significant economies of scale
in production.

Desirable research spaces

At a national conference on infections I attended in 2011, there were two
distinct zones; the “brand space”, where drugs reps talked about Pyostacine
— 56 pharmaceutical company booths were laid out in a way that forced the
1,500 doctors to follow a specific itinerary; and the “molecules space”,
where people talked about pristinamycin rather than Pyostacine. Symposiums
were held in the Einstein and Pasteur auditoriums. This is how drug
companies can exert some control over publicly funded research: they
finance medical conferences and influence their organisation. At the same
time, Sanofi progressively scaled down its research programmes on new
antibiotics and the improvement of existing ones. In 2004 this policy led
to the closure of its anti-infections research centre at Romainville, in
spite of opposition from chemists, biologists and technicians, who believed
the decision would prove disastrous from the point of view of public health
as well as employment. To reach the “scientific space” at the conference,
doctors had to go to the far end of the hall, passing at least 13 booths
that each reflected the exhibitor’s status and influence.

The main aim of exhibitors at such events is to show the scientific
superiority of their products. So symposiums bear the names of their
sponsors — Bayer, GSK, Sanofi — and are the forum where each company’s key
opinion leaders speak. To secure the services of influential medics, the
big companies’ lobbyists organise pseudo-scientific trips, among other
things. A Sanofi “medical advisor” said she had put together a group of
medics with expertise in a particular drug by targeting practitioners who
would influence other prescribers: “I said: ‘I’ve got ten places, so I only
want people who will generate €1m [turnover] or more.’” She took them to
Singapore, Durban, Cancun and Burma. “It feels silly saying it — and no one
does because we’re not supposed to — but that’s how you create real

One of Pyostacine’s KOLs, Dr Jean-Jacques Sernine, is an eminent expert on
infectious disease. He coordinates clinical trials for the pharmaceutical
industry (in particular Pyostacine for Sanofi) and provides expertise to
public health authorities. Though he has not evaluated the same drugs in
both contexts — which would have been a flagrant conflict of interest — he
belongs to a small group of experts who shuttle between the pharmaceutical
industry and public medicine. “Conflicts of interests are a permanent state
of affairs. As soon as you take an interest in antibiotics, dealing with
conflicts of interest becomes inevitable,” he said. “The whole thing would
be impossible without any exchange between us, the evaluators, at
administrative level and the pharmaceutical industry.” As both judge and
judged, medical experts are prisoners of their own expertise, bound to face
conflicts of interest.

This situation has repercussions for France’s national agency for the
safety of medicines and health products (ANSM) whose work relies on
experts. Its run-down offices in Paris’s northern suburb of Saint-Denis
contrast with Sanofi’s gleaming headquarters, a reflection of a profound
asymmetry socially and economically that makes it difficult to believe ANSM
can exert effective control. ANSM often lacks the time and the resources to
evaluate all the documentation submitted by drug companies in support of
applications for a licence to take a drug to market. Dr Sernine said of one
application: “There were 57 volumes, each of six or seven hundred pages,
which weighed 110kg and made a stack 2m high ... And that was only part of
the dossier.”

‘The strategy failed, not the antibiotic’

Clinical trials of antibiotics are opaque, and their results are
distributed selectively. Manipulation of data is not unknown. A trial of
Pyostacine for cases of pneumonia illustrates the problem: according to Dr
Sernine, the treatment was unsuccessful in seven patients who took
Pyostacine, compared to four for an alternative. According to Sernine (a
view shared by the medical director of the lab), the severity of some of
the patients’ conditions meant they should have received a different style
of treatment: “So the conclusion I came to was that it was the strategy
that failed, not the antibiotic.” But how can you judge the effectiveness
of a drug if the patients it doesn’t help are automatically disqualified?

It is hard for the ANSM to identify this kind of circular logic in
statistically complex reports, which have now replaced argument based on
medical evaluation of individual clinical case studies. In 2007
telithromycin, under the Sanofi brand name Ketek, was said be responsible
for severe side effects that led to patient deaths from liver problems.
(One of the people responsible for the clinical trials served two years in
prison in the US for having “invented” patients.) Some scientific managers
suggested that there were still “skeletons in the cupboard” where this drug
was concerned. This expression, used by a medical director of the group,
suggests that a degree of cynicism (though not universal) is to be found in
the company; the upper echelons of management have thoroughly internalised
its codes; senior managers put the interests of the company before
patients’ health in cases when the two conflict. Overall, there is a
selective amnesia about drugs. Unexpected side effects, biased clinical
trials and health scandals are forgotten, and clinical failures are given
less weight than successes.

This is one of the industry’s fundamental problems. Clinical trials — the
proof of the effectiveness of drugs — are conducted by the same people who
produce those drugs. This has been described as the “regulatory capture” of
the state by the companies. The same events recur every time there is a new
scandal: Stalinon (1957), Thalidomide (1962), Distilbène (1977), Prozac
(1994), Cérivastatine (2001), Vioxx (2004) — the question of the
independence of clinical trials comes up again and again. But the reforms
that follow never question the commercial ownership of drugs.

The problem is deeply rooted in the economic system, which is no more moral
about drugs than about oil or cosmetics. Not only because the same
shareholders are in control — L’Oréal is the biggest shareholder in Sanofi
since the recent departure of Total — but because the possibility of making
a profit from drugs sharpens the old antagonisms between utility and price.
While big pharma remains profit-driven, those antagonisms will continue to
escape the control of society in general, and those who are most concerned
— doctors and their patients.

Quentin Ravelli is a research fellow at the Centre National de la Recherche
Scientifique and the author of La Stratégie de la bactérie, Le Seuil,
Paris, 2015

This investigation was carried out as part of a doctoral research project
in sociology, during which I worked as an intern in Sanofi’s sales and
marketing department and factories.

Classic economics distinguishes between the use value and exchange value of
a commodity. Adam Smith distinguished between a diamond (high exchange
value, low use value) and water (low exchange value, high use value).

Employees’ names have been changed to preserve their anonymity.

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