Often protocols and informed consents have a reference to the declaration of Helsinki as an ethical guide for the conduct of a clinical trial. And clearly the declaration in all its versions have important guides for appropiate and ethical conduct. However in the newer versions controversy have emerged as the the requirements got more and more extensive.
The World Medical Association first adopted the Declaration in 1964 and, subsequently, has revised the document several times – most recently with the Helsinki-Brazil 2013 version.
However not everybody accept the later versions.
The US FDA rejected the 2000 and subsequent revisions, only recognizing the third (1989) revision, and in 2006 announced it would eliminate all reference to the Declaration. After consultation, which included expressions of concern, a Final rule was implemented April 28, 2008 replacing the Declaration of Helsinki with Good Clinical Practice effective October 2008 where the agency is amending its regulations on acceptance of foreign clinical studies not conducted under an investigational new drug application (IND) (non-IND foreign clinical studies) as support for an IND or application for marketing approval for a drug or biological product. The final rule replaces the requirement that these studies be conducted in accordance with ethical principles stated in the Declaration of Helsinki (Declaration) issued by the World Medical Association (WMA), specifically the 1989 version (1989 Declaration), with a requirement that the studies be conducted in accordance with good clinical practice (GCP), including review and approval by an independent ethics committee (IEC). The final rule updates the standards for the acceptance of foreign clinical studies not conducted under an IND and helps ensure the protection of human subjects and the quality and integrity of data obtained from these studies.
In practical terms the FDA sticks to the Good Clinical Practise – ICH E6 standard for the conduct of clinical trials
For the pharmaceutical industry however the bigger issue is in the requirements in the latest versions to provide experimental drug indefinitely to trial subjects if there was any benefit of the treatment. It means that a sponsor is bound to keep manufacturing and delivering the trial substance to the trial participants as long as it provide any benefit.
This can be almost impossible to do if the drug is not commercially viable. It can be very difficult to keep production, distribution and registrations going in the non-commercial quantities and it can cause substantial financial problems for a company.
The declaration of Helsinki-Brazil 2013 talks about the commitment to provide post trial access to the treatment in section 34.
2013 Version Section 33/34
In advance of a clinical trial, sponsors, researchers
and host country governments should make
provisions for post-trial access for all participants
who still need an intervention identified as beneficial
in the study. This information should also be
disclosed to participants during the informed consent
process. All study participants should be informed
about the outcome of the study.
Similarly the 2008 Declaration of Helsinki have provisions for post-trial access. but here the language gives a bit more flexibility to provide other beneficial interventions like alternative drugs or care for instance.
2008 Version Section 33/34
At the conclusion of the study, patients entered into the
study are entitled to be informed about the outcome of
the study and to share any benefits that result from it, for
example, access to interventions identified as beneficial
in the study or to other appropriate care or benefits.
Also in the 2004 Helsinki version there are access provision post study in section 30, but here there is no direct mention of the “intervention”.
2004 Version Section 33/34
At the conclusion of the study, every patient entered into
the study should be assured of access to the best proven
prophylactic, diagnostic and therapeutic methods identified
by the study.
The 2004 version looks like the 2002 version, but there is a footnote added to section 33 with an important clarification. The latest version of Declaration of Helsinki that is in line with the current GCP (ICH E6) standard from 1996 you will have to go back to the 2000-2002 Helsinki version where there is a clear reference to proven methods which favours existing therapies where there is more experience and therefore better proven
2000 Version (2002 update) Section 30
At the conclusion of the study, every patient entered into the
study should be assured of access to the best proven prophylactic,
diagnostic and therapeutic methods identified by the study.
It is important to assess very carefully which approach to take in each clinical trial and review the implications it will have for patients, institutions and the company. You can go with GCP only or implement any of the Declaration of Helsiki versions, but make sure that you can actually comply if you end up in a situation where the test therapy have some benefits, but will never be commercially viable.