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Fonte: Sifoweb. 8 gennaio 2009
Dopo anni di discussioni e attriti, la Food and Drug Administration
statunitense abbandona la Dichiarazione di Helsinki sui principi etici
per la ricerca medica che coinvolge gli esseri umani. Dallo scorso ottobre
la Dichiarazione è stata ufficialmente sostituita con il documento
Good Clinical Practice della International Conference on Harmonization.
"Ma la mancanza di regole chiare e condivise può creare
solo confusione nel mondo dei grandi trial internazionali", commentano
sull'ultimo del Lancet tre esperti di ricerca biomedica Jonathan Kimmelman
della McGill University, Charles Weijer della University of Western Ontario
e Eric Meslin della University of Indiana. Questo divorzio è un
problema non da poco.
Formulata nel 1964 dalla World Medical Association, la Dichiarazione di
Helsinki è stata (e cerca di continuare ad esserlo) la pietra angolare
dell'etica della ricerca umana. Nei sui quarant'anni e più di vita
è stata sottoposta a una serie di revisione e modifiche. La FDA
aveva già rifiutato la revisione del 2000 e nell'aprile del 2008
avevano annunciato che voleva abolire tutti i riferimenti alla dichiarazione.
Il problema però è che le nuove linee-guide adottate dall'FDA
sono meno rigide negli standard etici per le ricerche all'estero. Come
fanno notare i tre colleghi canadesi sul Lancet mancano dei principi fondamentali
della dichiarazione di Helsinki: la divulgazione dei risultati negativi,
la dichiarazione dei conflitti di interessi, la pubblicazione dei protocolli
degli studi e anche il controllo dell'uso del placebo che è stato
oggetto di diverse revisioni e di accesi dibattiti a partire dall'FDA
che si oppose a una restrizione dell'uso del placebo.
La separazione statunitense mette in discussione il futuro della Dichiarazione
di Helsinki. Il rischio è una "balcanizzazione degli standard
nella ricerca internazionale". Di fatto la nascita continua di
linee-guida e documenti guida nella ricerca biomedica non fa altro che
confondere le idee e mettere in luce la non obbligatorietà di tale
dichiarazione. Il documento della World Medical Association non ha infatti
nessun valore legislativo, ma si pone come una serie di raccomandazioni
da seguire nella ricerca clinica che deve essere finalizzata al bene della
popolazione ma nel pieno rispetto dei diritti del singolo individuo. Le
norme proposte sono solo una guida per i medici di tutto il mondo: i medici
non sono pertanto sollevati dalle responsabilità penali, civili
ed etiche previste dalle leggi del loro paese.
Il problema è che la FDA controlla un grossa fetta del mercato
farmaceutico mondiale e la mancanza di una guida standard nell'esecuzione
dei trial clinici internazionali può minare la salvaguardia dei
principi etici nelle sperimentazione clinica e lasciare campo libero agli
interessi del mercato.
"Chiediamo che il nuovo governo statunitense sospenda queste nuove
linee-guida in attesa di un'analisi delle conseguenze", concludono
i tre colleghi canadesi. "Nel caso che i nostri dubbi vengano confermati
la Fda dovrebbe ricongiungersi alla dichiarazione di Helsinki".
HELSINKI DISCORDS: FDA, ETHICS, AND INTERNATIONAL DRUG TRIALS
Kimmelman J, Weijer C, Meslin EM
The Lancet 2009; 373:13-4
ARTICLE
Since 1964, the Declaration of Helsinki has stood as one of the world's
most authoritative statements on ethical standards for human research. [1]
Drafted by the World Medical Association to provide medical researchers
with ethical guidance, the Declaration has undergone six major revisions,
most recently in October, 2008. [2] For many years the US Food and Drug
Administration (FDA) has required that foreign clinical studies supporting
applications for drug licensure comply with the Declaration. However, on
Oct 27, 2008, the FDA formally discontinued its reliance on the Declaration
and substituted the International Conference on Harmonization's Guideline
for Good Clinical Practice (GCP). [3]
The rationale behind the FDA's action is complex, and no doubt reflects
an effort to balance important interests and public-policy goals. Among
the FDA's reasons are the need to assure the quality of foreign data submitted
to the agency, a wish to prevent confusion among researchers when the Declaration
of Helsinki undergoes revision, and a worry that future modifications could
"contain provisions that are inconsistent with US laws and regulations".
[3] The FDA's latest action completes a process begun in 2001 when the agency
declined to recognise the 2000 revision, in part due to the Declaration's
restrictive stance on placebo-controlled trials in economically developing
countries. [4] The practical consequences of the FDA's current action are
unclear because the ruling applies to only a subset of clinical trials-ie,
international trials. Moreover, several countries that host such research
have regulations that endorse or emulate the Declaration of Helsinki.
Nevertheless, at a time when the volume of overseas trials is increasing,
[5] the FDA's new policy is troubling. First, the Declaration of Helsinki
has a moral authority that GCP lacks. The Declaration has long been recognised
as a leading international ethical standard for research. Whereas the World
Medical Association includes 85 national medical societies from every part
of the globe, the International Conference on Harmonization consists of
only voting members from the USA, the European Union, and Japan. Indeed,
the authors of GCP acknowledge the authority of the Declaration of Helsinki
when they state that a goal of GCP is "consisten[cy] with the principles
that have their origin in the Declaration of Helsinki". [6] The FDA
regulates the largest drug market in the world and we worry that its replacement
of the Declaration of Helsinki with a less morally authoritative document
may cause others to follow suit, thereby undermining international ethical
standards for research.
Second, the Declaration of Helsinki has a breadth and depth that GCP lacks.
[1] For sure, GCP covers similar topics to the Declaration, but the focus
of GCP is regulatory harmonisation, not the articulation of ethical commitments.
Careful examination of the two documents reveals several important ethical
issues that are addressed in the Declaration about which GCP is silent.
Panel
Requirements in latest revision of Declaration of Helsinki [2] but absent
in GCP [6]
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Investigators to disclose funding, sponsors, and other potential conflicts
of interest to both research ethics committees and study participants |
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Study
design to be disclosed publicly (eg, in clinical trial registries) |
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Research,
notably that in developing countries, to benefit and be responsive
to health needs of populations in which it is done |
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Restricted
use of placebo controls in approval process for new drugs and in research
done in developing countries |
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Post-trial
access to treatment |
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Authors
to report results accurately, and publish or make public negative
findings |
Thus
reliance on GCP rather than on the Declaration of Helsinki may result
in less protection for research participants. If so, the FDA's action
might lower the bar for international research under its purview-a scenario
that has worried previous commentators. [7, 8]
Third, the FDA's departure from the Declaration of Helsinki could undermine
its stated goals of clarity and regulatory harmonisation. For example,
if many countries continue to use the Declaration, US researchers will
encounter the same "confusion" that the FDA is attempting to
prevent with its new rule. Similarly, should other countries follow the
FDA's lead and abandon the Declaration of Helsinki, the result could be
the balkanisation of ethical standards in international research.
In view of these concerns, we suggest the new US administration suspend
this rule pending a review of the implications for US-sponsored research
overseas. If such review confirms our concerns, the FDA should be directed
to rejoin the international community in requiring that studies be done
in accordance with the Declaration of Helsinki. We also see an important
role for major medical societies-though they lack regulatory authority,
collectively these organisations can give voice to the commitment of medical
researchers to the Declaration's high ethical standards. The American
Society of Gene Therapy is considering policy on this issue [9] and others
should follow suit.
References
1. RE Aschcroft, The Declaration of Helsinki. In: EJ Emanuel, C Grady
and RA Crouch et al., Editors, The Oxford Textbook of Clinical Research
Ethics, Oxford University Press, New York (2007).
2. World Medical Association,
Declaration of Helsinki (October, 2008) (accessed Oct 25, 2008)..
3. Department of Health and Human Services, Food and Drug Administration,
Human subject protection; foreign clinical studies not conducted under
an investigational new drug application. Fed
Reg (April 28, 2008) 22800-16. (accessed Nov 9, 2008)..
4. Department of Health and Human Services, Food and Drug Administration,
Guidance
for industry: acceptance of foreign studies (March, 2001) (accessed
Nov 9, 2008)..
5. FA Thiers, AJ Sinskey and ER Berndt, Trends in the globalization of
clinical trials, Nat Rev Drug Discov 7 (2008), pp. 13-14. Full Text via
CrossRef | View Record in Scopus | Cited By in Scopus (6)
6. International Conference on Harmonization, Guideline
for good clinical practice (e6) (1996) (accessed Oct 25, 2008)..
7. National Bioethics Advisory Commission, Ethical and policy issues in
international research: clinical trials in developing countries, vol
1 (2001) (accessed Oct 25, 2008)..
8.
Nuffield Council on Bioethics, The ethics of research related
to healthcare in developing countries (2002) (accessed Nov 9, 2008)..
9. T Friedmann, The ASGT and ethical codes for research, Mol Ther 16 (2008),
pp. 1643-1644. Full Text via CrossRef | View Record in Scopus | Cited
By in Scopus (1)
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