Industry and Clinical Trials
Robert M Califf MDDirector, Duke Clinical Research InstituteDuke University Medical CenterDurham, NC
Salim Yusuf MDProfessor of Medicine,
McMaster University Hamilton, ON, CanadaFrans J Van de Werf MD
Professor and Chairman, Department of Cardiology University Hospital Gasthuisberg Leuven, BelgiumValentin Fuster MD
Director, Cardiovascular InstituteMount Sinai Medical CenterNew York, NY
•The medical products industry?
•The academic community?
• Is all this being done
On behalf of patients
Or to generate profits for the medical products companies?
Who controls the evidence for evidence-based medicine?
The "era of evidence-based medicine"
Rob Califf
• Who is generating this evidence, and what is the motivation?
• How are studies designed?
• How are they presented to the public?
• Is there a fair balance between patient interests and sponsor interests?
20 years of success
• 20 years ago, we had almost no treatments in cardiology that were shown to save lives
• Research has made huge strides in cardiology by validating those ideas in large clinical trials
Salim Yusuf
Trials funded by industry
Industry trials are fine if
•Studies are done independently
•Results are presented fairly
Salim Yusuf
"We have to be very careful that we work with industry
rather as opposed to working for industry."
Industry independence
• We are now more dependent on industry
• Industry is less dependent on academia
• Most important trials are performed correctly
Frans Van de Werf
• All important new agents have been made by industry
• You need to have an industrial partner for large-scale production of important agents
No real alternative
Frans Van de Werf
"We have to work with industry but it can be done in a
correct way."
Overemphasis on drug and device trials
• We have no clinical trials informing us about diet
• Industry is designing trials based on the products they want to sell
• Still, industry research has achieved much in the field
Valentin Fuster
Public-private partnerships
• We need to link industry more with the federal government
• Trials should focus on the patient, not solely on pharmacology and devices
• The problem is trials are very expensive
• It would be ideal to bring industry and federal organizations together to share the cost of trials Valentin Fuster
The system
Rob Califf
• Much of the advance in cardiovascular medicine is due to developing new medical products
"I would certainly be a strong advocate that the capitalistic system is an effective system, obviously within certain bounds."
Fundamentals overlooked
• Clinical trials of lifestyles
• Clinical trials of alternative medicine
• Long-term outcomes
• Combining therapies in the same patient
Rob Califf
Decoding journal articles
• It is sometimes difficult to learn how a trial was conducted
• Important trials should be clear about
The structure of the trial
Who developed the study and where was the data analyzed
Frans Van de Werf
Collaborating with industry• Industry people may know the drugs or
devices better than any of the investigators. Investigators must maintain editorial independence while collaborating
• Investigators must maintain editorial independence while collaborating
• Industry should recognize the benefit of collaborating with a strong, independent academic group
Salim Yusuf
Editorial independence
• Data management should be run independently of industry
• Must maintain editorial control
We wrote a draft manuscript before industry even knew the results of the study
They could comment but we had the final word.
Salim Yusuf
• The ideal is symbiosis with the final word with the academic group
•Industry can find subtle ways to put pressure
Symbiosis
“A tough and strong academic group on one hand and a sensitive industry on the other hand can strike the right balance" Salim Yusuf
Outside cardiology
• Independent steering committees and data safety monitoring committees are relatively new ideas
• Academic communities often have little say
Rob Califf
Supplements
• Ghostwritten articles are worrisome
• Supplements should not relate to a single product
Focus on a single disease state to an end point
Discuss all the possible strategies involved
Valentin Fuster
Ghostwritten articles
• The “non-writing author, non-author writer” syndrome
• If the editors at a journal are familiar with the subject
matter, it should not be hard to detect ghostwritten articles
“We will do our best to identify these articles, I can promise you."
Frans Van de Werf
• Primary manuscripts are usually written by the researchers
• The problem lies in secondary publications, summaries, and supplements
Secondary publications
"I would be happier if we had 20 or 30 percent fewer
publications but each of those publications were more substantive" Salim Yusuf
• In the US, sales forces cannot talk about off-label claims but can present off-label research
• Supplements are big money-makers for journals
Motivating factors
Rob Califf
• If an article is ghostwritten, the ghostwriter should be first author
• It should be clear that the article was not written by the researchers
Clear authorship
"I might say my suggestion has not been embraced by
people who are sending these articles in"
Rob Califf
• If the government can create the playing field for clinical trials, industry would respond
• Government consortia could reduce cost and provide a balance between the public need and the private need
Public-private partnerships
Rob Califf
Generic questions
• We have to answer generic questions in addition to product-oriented questions
• 2 solutions
Joint partnership between academic, industry, and government
Factorial designs in studies, which are not utilized enough
Salim Yusuf
Useful approaches
• In every instance, propose a factorial design with an important generic question
Half the companies accept this
• Epidemiological studies linked in with the trial
Salim Yusuf
"Government can also bring into the picture certain checks and balances that keep us all on the straight and
narrow."
Government bureaucracy
• Government trials require years of reviews and committee meetings so it is hard to get things done
• Trials are designed with political considerations in mind instead of focusing on answering a single question
Rob Califf
Striking a balance
• Investigators must judge if it is worth the effort to go through the government
In Canada, we get little money, but also very little interference
• Some flexibility is needed on the part of government, because it's in everyone's interest to cooperate
Salim Yusuf
Public pressure
• Government agencies are moving in the direction of partnering with industry
• These agencies are taking a lot of time in terms of the process
• Public pressure to test promising therapies and devices should create systems that will be probably less bureaucratic and much more expeditious
Valentin Fuster
Review Process
• Pool of qualified reviewers is extremely small and very busy
• We must bring the young generation of scientists into the review system with the help of more senior people
Valentin Fuster
European Perspective
• Less of a tradition of cooperation between government and industry in Europe
Multiple countries mean additional bureaucratic hurdles involved in trials
• Hopefully in the future a more unified Europe will make it easier to get funding from European organizations for industry-sponsored trials
Frans Van de Werf
•Cardiovascular medicine a leader in academic independence while working with industry
•Ensuring independence requires
The presence of an independent steering committee
Management of the data and analysis independently of industry
Publication certified by the investigators, with industry having input but not the final say
Summary – academic independence
Rob Califf
Summary - partnerships
• Government infrastructure with industry funding will be a critical step in the future
• Ghostwriting should be discouraged but acknowledged when it happens so readers are aware of the source of the message
• Public pressure can help move public-private partnerships to answer questions of public health beyond medical products
Rob Califf
"Whenever possible, consider factorial designs so that we will not just move the drug agenda forward, we’ll also move the broader agenda of improving patient outcomes."
Factorial design
Salim Yusuf
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