conflitto di interessi in epidemiologia · conflitto di interessi in epidemiologia corrado magnani...
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Conflitto di interessi in epidemiologia
Corrado Magnani e Francesco Barone-Adesi
Università del Piemonte Orientale - Novara
Il conflitto di interessi
• “Conflicts of interest are defined as circumstances that create a risk that professional judgments or actions regarding a primary interest will be unduly influenced by a secondary interest… Conflicts that are disclosed but not eliminated or managed can continue to pose risks to judgment and undermine public trust.” (IOM 2008)
• COI is a condition, not a behavior, in which the circumstances and not the outcome determine the presence of COI.
I diversi attori / ruoli nella ricerca e post-ricerca (biomedica)
• Ricercatore• Istituzione• Finanziatore• (Industria)• Editoria scientifica• Divulgatori (linee guida)• Organismi regolatori• Definizione limiti e standard• Valutazione conseguenze (tribunale)
A COI does occur if a researcher has a direct financial tie to
the success of a product of research because this tie could
bias his or her judgment and harm the integrity of the
research.
In other words, the situation described in the example is not
a potential COI that could result in a real COI; it is simplya COI that could result in real bias or harm.
McCoy JAMA May 2, 2017 Volume 317, Number 17 1721
The notion of a potential COI reflects the mistaken view that a COI exists only when bias or harm actually occurs.
Effetti del COI
“If COI is not managed effectively it can cause authors, reviewers, and editors to make decisions that, consciously or unconsciously, tend to serve their competing interests at the expense of their responsibilities in the publication process, there thereby distorting the scientific enterprise.
This consequence of COI is especially dangerous when it is not immediately apparent to others.
In addition, the appearance of COI, even where none actually exists, can also erode trust in a journal by damaging its reputation and credibility”.
[World Association of Medical Editors (WAME)]
Not only an economic issue
• “We are restricting ourselves to asking directly about competing financial interests, but you might want to disclose another sort of competing interest that would embarrass you if it became generally known after publication” (BMJ)
Ronald Fisher
Quanto sono rilevanti i fondi dell’industria nella ricerca biomedica?
(Chalmers Lancet 2009)
Ruolo dell’industria nella ricerca biomedica USA
Bekelman et al. JAMA 2003
Bekelman et al. JAMA 2003
In che maniera ricercatori con COI possono alterare i risultati della ricerca
biomedica?
• Favorendo la produzione di risultati positivi, vantaggiosi per il finanziatore (tipico nell’industria farmaceutica)
• Favorendo la produzione risultati dubbi/negativi, per enfatizzare l’incertezza riguardo un tema e avere così un pretesto per rallentare l’implementazione di azioni preventive (es. industria del tabacco)
Barnes and Bero, JAMA 1998
Cambiare i criteri di classificazione di una patologia per
aumentare il numero dei pazienti: le Pre-diseases
• Le linee guida del 2003 avevano proposto unanuova classificazione per le persone con pressione sistolica di 130-139 mm Hg o pressione diastolica di 80-89 mm Hg
• La giustificazione: più alta è la pressionesanguigna, più alto è il rischio di malattiecardiovascolari. In teoria gli individuiclassificati come “pre-ipertensivi” non dovrebbero essere trattatifarmacologicamente, ma dovrebbe essereofferto loro aiuto per cambiare stile di vita.
• 1/3 degli adulti nei paesi occidentali sono pre-ipertesi (150 ml di persone in EU e US)
• Nel febbraio 2011 a Vienna (conferenza mondiale) è stato presentato un trial che ha prodotto modesti risultati con pre-ipertesi trattati con un sartanico.
• I responsabili del trial e gli organizzatori della conferenza (American Society of Hypertension) hanno multipli interessi nell’industria (alcuni sono semplicemente dipendenti dell’industria)
• Anche il comitato che ha elaborato le Linee Guida del 2003 era composto da 12 membri, di cui 11 con multiple relazioni con l’industria.
COI al di fuori dell’industria farmaceutica
Between 2001 and 2006, as part of their litigation strategy to convince juries to dismiss mechanics’ claims for compensation for asbestos diseases from exposure to asbestos containing brake linings, General Motors, Ford, and Chrysler sought out and paid more than $23 million to Exponent and ChemRisk mainly to reanalyze previously published research. (Egilman and Bohme 2006 )
Editors with at least four research publications say they have received a letter advising them against “publication or other distribution” of data and draft documents. The warning, including a vague statement about “consequences” that could ensue if the advice is ignored, is signed by Henry Chajet, an attorney at the Patton Boggs firm in Washington, D.C., and a lobbyist for the Mining Awareness Resource Group, which works on behalf of the mining industry.
http://www.litigationandtrial.com/2012/02/articles/litigation/scientific-journal-defamation/
La creazione del dubbio
“Even the very best scientific evidence can have less persuasive power than corporate lobbies. A major global problem is the fact that industries fund research geared to create doubt and prevent needed action to protect public health. Industry suppression of scientific data creates misinformation and skews priorities for research and public health interventions” (Margaret Chan, Director-General, WHO.Address to the sixty-sixth world health assembly, Geneva, Switzerland, 20 May 2013.
Epidemiology under attack1) Criticisms of epidemiology as a science (Taubes 1995,
Kabat 2008);
2) small or nonexistent health risks are unjustifiably
highlighted and hyped by researchers who have a vested
interest in continued research funding and the need to publish
to benefit their careers (Boffetta et al. 2008; Kabat 2008;
McLaughlin 2010, 2011;)
3) Epidemiology specifically has been criticized for a tendency
to produce false-positive results (Boffetta et al. 2008, 2009;
Ioannidis 2005; Kabat 2012; McLaughlin and Tarone 2013).
4) Attack to IARC (classification method and composition of
working groups)(Erren 2011; McLaughlin 2010, 2011);
Cosa può essere fatto?
1. Ammettere che esiste un problema
2. Dichiarazione di tutti i possibili conflitti di interesse
3. Accordi trasparenti nel caso di collaborazioni con l’Industria
4. Incompatibilità di specifici ruoli con un conflitto di interesse
5. Creare degli specifici organi di vigilanza
6. Favorire il controllo dei risultati e loro replicazione da parte di
ricercatori Indipendenti
Dichiarazione conflitti di interesseInternational Commitee of medical Journals Editors guidelines (2001)
• “Full disclosure of the sponsor’s role in the research”
• “Assurance that the investigators are indipendent of the sponsor, are fully accountable for the design and the conduct of the trial, have indipendent accesss to all trial data, and control all editorial and publication decisions”
Editoria scientifica e COI: una storia con alti e bassi. L’esempio del NEJM
• 1980 Editoriale di Relman
• 1984 primo COI disclusure at NEJM
• 1990 divieto NEJM per gli autori di editorial e review di COI
• 2002 Drazen allenta le regole sul COI al NEJM
• 2015 Serie di articoli di Rosembaum su NEJM contro la regolamentazione del COI
Esempio di modulo per la dichiarazione del conflitto di interessi
• Virtually all transactions between drug industry and doctors in US reported and publicly available online
• Just in the last 5 months of 2013 financial transactions for $3.7bn to doctors
• This may bring to a rise in the number of physicians unwilling to accept industry payments
Is COI disclosure sufficient?
“The problem with COIs is not the lack of disclosure but the existence of the conflict itself. In fact, assuming that “sunlight is the best disinfectant” and making disclosure the standard fare may exacerbate the problem. First, some physicians are not embarrassed to have their financial arrangements aired widely; some even consider it a badge of honor to be paid handsomely by industry.”
• The Committee on Publication Ethics (COPE) was established in 1997 by a small group of medical journal editors in the UK but now has over 10 000 members worldwide from all academic fields. Membership is open to editors of academic journals and others interested in publication ethics.
• COPE provides advice to editors and publishers on all aspects of publication ethics and, in particular, how to handle cases of research and publication misconduct. It also provides a forum for its members to discuss individual cases. COPE does not investigate individual cases but encourages editors to ensure that cases are investigated by the appropriate authorities (usually a research institution or employer).
Weaknesses of COPE• COPE recommends that, if a conflict of interest comes to light after
publication of an article, the journal should publish a Correction
disclosing the conflict of interest.
• COPE provides a complaint mechanism regarding contraventions
of its Code of Conduct. It also has enforcement ability, although a
weak one.
• If a COPE member is not willing to comply with its Code of
Conduct, COPE “will aim to discuss that with the member, and will
ask them to consider their membership of the organization.
• However in several recent cases COPE categorically notified the
journal that it was free to disregard COPE’s recommendation and
continue as a COPE member without any consequences.
• Without accountability, COI disclosure requirements lack credibility
• COPE also protects its member journals with anonymity, when it
reports the cases on its website. There is no transparency and no
public accountability.
Importanza di avere un «Agreement» scritto quando si inizia una collaborazione con l’industria
• Accordo chiaro sui metodi che verranno utilizzati per la raccolta dei dati, la loro analisi e interpretazione
• Presenza di uno Steering comittee
• Diritto di accesso a tutti i dati rilevanti da parte dei ricercatori
• Accordo che i risultati verranno comunque pubblicati
• Nessuna clausola di confidenzialità che riduca la libertà dei ricercatori
L’importanza degli organi di vigilanza: il caso Lucentis vs Avastin
• In the period 1998-2004, in US there was a four-fold increase of the number of pharmaceutical company-sponsored meetings and talks that featured doctors as speakers.
• At present, industry pays for well over half of the expense of doctors’ continuing medical education in US.
The issue of Continual Medical Education
The initiative of BMJ of banning educational papers funded by industry. “Finally, we want to encourage a shift in the culture of medicine. We think that we can help to do this by promoting authors without financial ties to industry and offering them appropriate prominence and visibility.”
BMJ 2014;349:g7197
Changes in Continual Medical Education• Starting in January 2013, in Canada industry would not be permitted
to attend CME content planning meetings nor be allowed to “have any role” in CME program content development.
• In Canada attempts to allow industry to contribute only with unrestricted funding to a central pool within the larger organization
• In US attempts to prohibit physicians with financial conflicts of interest from planning or teaching CME. The US Accreditation Council on Continuing Medical Education did recommend this in 2003.
• American Medical School Student Association (AMSA) now grades medical schools on their creation of a “pharma-free” environment, issuing annual report cards on conflict-of-interest policies and curricula”
• As of 2014, some these recommendations have been adopted by 79 medical schools, including Harvard.
E noi singoli ricercatori cosa possiamo fare per favorire questo cambiamento
culturale?• Ammettere che il COI è un problema pervasivo nella
ricerca biomedica.• Imparare a valuatare criticamente la letteratura scientifica
tenendo conto di possibili COI• Imparate a valutare criticamente i nostri possibili COI.• Essere un esempio di trasparenza per gli altri ricercatori.• Sensibilizzare colleghi e studenti al problema del COI.• Essere pronti a denunciare eventuali COI non dichiarati
e casi di malpractice alla comunità scientifica e allasocietà civile.
Gruppi di ricercatori • Public Employees for Environmental Responsibility, for example,
representing local, state and federal researchers in the U.S., have filed a legal petition to require the U.S. Department of Agriculture to adopt policies to prevent “political suppression or alteration of studies and to lay out clear procedures for investigating allegations of scientific misconduct”
• Government scientists in Canada are seeking to protect scientific integrity through collective bargaining. The Professional Institute of the Public Service of Canada, representing 15,000 federal government scientists, engineers and researchers has tabled a proposal that would obligate the government to negotiate scientific integrity policies.
• The Center for Science in the Public Interest• Retraction Watch• E molti altri…
Conflitto di interessi:
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