For those of us in the North Carolina office, the frosty mornings of fall are finally upon us. We all know that at this time of year, if you blink, New Year’s Eve has already come and gone. It’s the speedy arrival of the Holidays that causes us to reflect on how quickly things can change, whether the seasons, the dishes on the Thanksgiving table, or yes, even the regulations governing your Trial Master File (TMF). But change also has a habit of focusing us on the things we are truly thankful for.
The traditional Thanksgiving menu has been far from static. Like most traditions, the ‘Thanksgiving Story’ and the meal contained within are more legend than historical reality—Americans did not fully embrace Thanksgiving nationally until the 1860s. As far as the existing historical accounts go, there are quite a few myths to be busted:
- There is no historical mention of turkey as the centerpiece of the original Thanksgiving (where English colonists and Wampanoag Native Americans joined together for a harvest festival in 1621). There is only mention of ‘wild fowl’ – which could have been any game bird. Venison, in fact, is the only protein specifically mentioned.
- Although semi-wild pumpkins and cranberries were native to the New World, both would probably have been prepared much differently than today, as the colonists would have coped with a limited availability of sweeteners to round out their bitterness.
- Corn was bountiful and well known to Native Americans, but was harder and starchier than today’s sweet corn. The colonists would have ground and boiled the dried corn into mush with some salt. As colonies became more established in the New World, they would have sweetened it with expensive imported molasses.
- Fish and shellfish would have played a dominant role in the first Thanksgiving. Oysters, specifically, where one of the few foods colonists would have found familiar and abundant.
- Sorry, no mashed potatoes for you! Although native to North America, Europeans discovered the tuber by way of Europe when brought back by the Spanish. Although the Wampanoag would have eaten similar wild starchy roots, the colonists have been suspicious of these often-bitter roots unless seriously hungry.
Like the dishes on the Thanksgiving table, the regulation of clinical trials and the TMF is far from set in stone; the recent release of the 2017 ICH GCP E6(R2) is the most significant and recent example of this constant change. Although the changes, which went into effect this past June, represent a serious step towards modern ‘paperless’ research, their main goal remains the same: to “provide a unified standard for the European Union (EU), Japan, and the United States [allowing for the] mutual acceptance of clinical data by regulatory authorities.” Here are some of the most important changes impacting your TMF:
- eTMF technology is finally accounted for and contemporaneous filing is now the expectation: “The sponsor and investigator should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should provide for document identification, version history, search and retrieval.” (8.1)
- It is confirmed that there is no forthcoming ‘checklist’ of one-size fits all essential documents: “Essential documents for the trial should be supplemented or may be reduced where justified (in advance of trial initiation) based on the importance and relevance of the specific documents to the trial.” (3.3.1)
- A definition of a certified copy has been created (to address conversion/format changes of electronic items): “A copy (irrespective of the type of media used) of the original record that has been verified (i.e., by a dated signature or by generation through a validated process) to have the same information, including data that describe the context, content and structure, as the original.” (8.1)
- The Principal Investigator is fully responsible for upkeep of source documents and trial records. Most importantly, the new guidance mentions the importance of ALCOA attributes (attributable, legible, contemporaneous, original, and accurate) when it comes to a site’s files. (4.2.5, 4.2.6, 4.9.0) There is also significantly more detail about who has ‘ownership of TMF documents: “The sponsor should not have exclusive control of the Case Report Form, and the Investigator should control their essential documents before, during and after the trial.” (8.1)
Change can be uncomfortable, but oftentimes it’s for the best (aren’t we all glad that corn mush is no longer on the Thanksgiving table?). The advance of new technology and the regulation to support it, specifically surrounding the TMF, can seem relentless, but with this relentless pace comes the promise of accelerated clinical development. At LMK, we’re happy to see this progress, but firmly believe that technology alone is never the best solution. We’re truly thankful it’s our job to be the ambassadors of change in our industry; empowering the best people with the right tools—and ultimately uniting patients with life-changing treatments.