The FDA and the Declaration of Helsinki

It's not new, however awareness of the following is not yet all that wide-spread...

The FDA has abandoned the Declaration of Helsinki

After years of a power struggle between the American law makers and the World Medical Association (WMA), in 2008 the US Food and Drug Administration (FDA) took the drastic step of removing references to the Declaration of Helsinki from their documents. In April 2008, the FDA published a regulatory change ending the need for clinical trials conducted outside of the US to comply with the Declaration of Helsinki, for them to accept the data from those trials.

When the WMA published the fourth revision of the Declaration (1996), the FDA chose the side of the pharmaceutical industry, and fought the addition to the 1996 Declaration which intended to limit the use of placebos in clinical research where proven interventions had become established. 

In the Declaration of Helsinki 2000, the WMA states that investigational products "be tested against those of the best current prophylactic, diagnostic, and therapeutic methods." They continue to say that "this does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists."

The FDA preferred the 1989 version and publicly criticized the Declaration. Indirectly, they gained support from the EU regulators, who in their 2001 Clinical Trial Directive (2001/20/EC)  AND in their 2005 GCP Directive (2005/28/EC) refer to the 1996 version of the Declaration of Helsinki, blatantly ignoring the 2000 version and the 2002/2004 notes of clarification.

In 2006 the FDA pre-announced their intention to remove all references to the Declaration of Helsinki from their regulations. The WMA published their sixth (2008) revision on October 18, 2008, not budging to the pressure of the FDA, who published the Final Rule in April 2008 . The Final Rule became effective October 27, 2008:

"The final rule replaces the requirement that [non-IND foreign clinical 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."

The use of placebo groups overseas is justified by arguing that patients in poorer countries would not have access to existing standard treatments outside of the trial. The trial simply compares a new treatment against the existing “standard of care” in the country where the trial is conducted. The result however is that a study that is considered unethical in the US, IS allowed to be run in another country.

You can argue that a country is allowed to set higher than the internationally accepted minimal standards for within its own territory. This, however, is a situation where a country is taking the more and more accepted international standards, and decides that as far as they are concerned, data derived from clinical trials that do not live up to those international standards, is now acceptable to them.

Pharmaceutical companies have responded generally positive to the FDA's change in point of view, some even with immediate effectiveness removing the Declaration of Helsinki from their protocols.

There are generally two advantages for the pharmaceutical company for doing placebo controlled trials.

• It is easier to show that a drug is better than placebo than existing therapies. Active comparator trials require more patients and consequently more time and money.
• If the existing treatment turns out to be more efficacious, it enforces the market position of the competitors product.

We should be cautious, however, to take the word of the FDA as gospel for the rest of the world. Just because the FDA is saying that they accept foreign clinical studies even if they do not adhere to the Declaration of Helsinki, does that mean we should all collectively abandon the Declaration? Do we, each, not have the personal and individual responsibility to never let there be any doubt about the ethical standards we apply to our research involving human subjects?

Participants in a trial are providing a valuable service to the investigators and the industry. This has always implied a special requirement that the investigator protect the interests of the subjects.

The FDA's change in what they accept from the rest of the world does not automatically have to change what the rest of the world offers to the FDA.wow gold

EMEA and FDA strengthen collaboration on inspections

The FDA (US) and the EMEA (EU) have started a Bilateral GCP Initiative as of September 1st, 2009. This program has been enabled by confidentiality arrangements between the EU and the FDA which deals with GCP-related information contained in applications for scientific advice, orphan medicines designation, pediatric investigational plans and marketing authorisation or postauthorisation activities of significant public health interest.


The intention of this Joint Inspection Program is that it will help to protect clinical trial subjects in the growing globalisation of clinical research. Most of the time, the same trials are used for Marketing Authorisation Applications (MAA) both in the US and in the EU. This initiative intents to ensure that those trials are executed uniformly, appropriately and ethically.


It concerns a pilot phase of 18 months, after which a joint assessment will lead to modifications and amendments to the scope and process, as needed.


The key objectives are:
 - To conduct periodic information exchanges on GCP-related information
 - To conduct collaborative GCP inspections
 - To share information on interpretation of GCP


The two regulators are currently inviting companies who are planning to submit applications fairly simultaneously to both regulatory authorities between September 2009 and September 2010, to volunteer to partner in this pilot. wow gold

FDA 1572's continued use, though expired

The FDA 1572 form has an official Expiration Date: May 31, 2009. Almost 6 months ago!

However the FDA is reporting on their website that "FDA has OMB approval to use the form until 8/31/2011".

This means that the form will not be updated, it will continue to be used in it's current form, sporting the current expired expiration date, until end of summer 2011.

Though being an FDA, therefore US form, this form is widely used outside of the US, even though, by signing it, non-US investigators are agreeing to work in accordance with the US Code of Federal Regulations (specifically 21 CFR parts 50, 56, 312.62, 312.64, 312.68 and 312 as a whole).

REMINDER:
At audits and inspections, by the way, still often a 2 page version of the 1572 is found, with an original signature. This form needs to be double sided, signature on the back, not enabling changes to the details on the front without having to sign again. In May 2010, the FDA stated that either a double sided 1572 or a two-page document "is acceptable; however, FDA recommends that a two-page document be stapled so that there is no question about what form the investigator signed."
 Any updates warrant a new FDA 1572 to be created, and newly signed and dated.wow gold

Welcome to Clinical Research Weekly!

Today is the birth of this new blog.

This blog is started to share little bits of Clinical Research news on a weekly basis.

Everyone working in Clinical Research (CR) is just too busy to keep up with what's going on in the rest of the world. This blog is the outcome! Just a couple of minutes read every week gets you a bit of news, a reminder, or just an interesting little tidbit.

My name is Eric. I've been working in CR for over 15 years, having done jobs like data manager, CRA, Clinical Team Leader, Clinical Research Trainer, Medical Advisor, etc.

The intention of the writings is to be educational and/or informative.

Please leave comments as you see fit, I'm very open to suggestions or comments.

Welcome, and here's to a successful blog!
Eric wow gold