The advancement of sample tracking is becoming so complex that we’ve reached the limit of our use of spreadsheets. Systems that can do such tasks are inevitable. The simplicity of counting the number of samples (how many do I have?) and the simplicity of knowing where the sample is (the “chain-of-custody”) are two very easy components of a sample tracking system.
The third component needed within such a system is the ability to incorporate the regulatory component of sample tracking – the “what can I do with the sample” factor. Or, in other words, “what is the consent obtained for that sample?” This is the ongoing investigation; taking a physical single sample and placing it against the right piece of paper, signed by the right subject, telling me what procedure(s) can be executed against that sample. The issue falls to the informed consent document and how it is written and changed over the course of a single study.
Let’s break it down: We have the simple Main Study Informed Consent (and ONLY the Main Study Consent) – the document where the subject agrees to participate in the clinical study. This document outlines what is required, as it relates to the number of samples drawn over a specified period, as well as the volumes extracted from the subject. That informed consent is universal for the study. EVERY sample is taken for the use of the study and EVERY test procedure relates to that study. Any remnant stored for a finite number of months, approximately one year post the last subject last visit (LSLV) or on, or about, the time the clinical study report is issued.
Exploring Future Use Consent
In the advancement of new procedures or biomarkers that could provide us more insight into the investigational product, comes the need for future use consent. This can complicate the issue. That “future use” consent, in its rudimentary form, describes if I have remnant samples left. After the sample is tested to satisfy the defined outcomes listed for the study, I can then appropriately store that sample for a predetermined length of time (the FDA has a guidance of 15 years), and use it in tests associated to the same indication. So, this consent takes effect when the Main Study ends and the clock starts after the trial reaches Last Subject Last Visit (LSLV).
Still, it’s not as difficult as both the Main Study consent and the Future Use consent, in the above context, where all associated samples are collected for the subject. The third type of consent affecting samples is the Genetic Use consent. Like Future Use, Genetic Use carries the stipulation that only genetic testing may occur to those samples. In many ways, this is like Future Use consent as the increased number of procedures that a lab can do against varying sample types is coming to the point where you can get genetics out of almost anything! Genetic is stipulated because certain countries have greater restrictions on genetic testing.
Still, to keep it simple, let’s assume that Genetic Use consent falls in-line with Future Use (from a maintenance timeframe perspective). Thus, once the main study use is completed, the sample is placed in storage until the need occurs to resurrect the sample to perform test(s) against that sample in the predetermined timeframe. And in this scenario, the predetermined timeframes all are in sync with the other.
The simplicity of this is diagramed in Figure 1:
The Difference between Genetic and Future Use is not in the Timeframe
Figure 1 depicts only a single sample from a single subject who has stated “yes” for all consents: Main Study, Future Use and Genetic Use. And, in this scenario, the Genetic and Future Use timeframe coincide. To ensure the sample is available for the needs of the study, post-LSLV, the sample remains under the Main Study consent. This further guarantees retesting requests can be fulfilled for the Main Study. After the (approximate) one year duration, and remnant samples still exist, the sample falls to the Future Use/Genetic Use consent, but the elapsed clock had already started back at LSLV.
To begin the complex development, the subject only needs to answer “no” to one of the consents. So, the Main will be “yes,” else the subject will not even exist in the study. The Future Use could be “no” and the Genetic could be “yes,” or vice versa; or both Future Use and Genetic Use maybe “no.”
Under this scenario, if both the Genetic and Future Use are both “no,” then, from Figure 1, the destruction of the sample WILL occur at timepoint “D.” Since, in this scenario both the Genetic and Future Use have the same time element into the future, the destruction of the sample will occur at timepoint “F.” The difference between Genetic and Future Use is not in the timeframe, the difference would be the list of procedures that could be done against the sample. Genetic Use as “yes” implies, at least in this writers’ experience, that there is an implied timeframe that extends into a point in time beyond LSLV. As I stated, in this scenario, the timeframes for Future Use and Genetic are the same (this is item “E,” in Figure 1).
The uses (“what can I do with this sample”) between Future Use or Genetic Use would be articulated in the Informed Consent documentation or the protocol.
Can I articulate that in an application and codify the interpretation of the document? Do I want to codify that into an application so that the end user need only press a button for a report? To do that would require a standard text used in the Informed Consent documents so that the interpretation would always be the same. As a company, can we do that? The simple answer is “yes,” but in the field of clinical trials the answer is not that simple and is probably “no.” For a protocol and the accompanying informed consent forms to be used they must pass ethics boards in various countries and in various institutions. This is where interpretations of the consents get altered. Once approved, and used within that clinical site, that interpretation would need to be “in-hand” of the sponsor. In that way there is no question as to what testing can be done to the sample.
In conclusion, our experiences with sample tracking management there are two possibilities emerging:
1) Place sufficient Informed Consent information in the application (or system) that will allow sample selection based on which subject has stated ‘Yes’ for Future Use or Genetic Use. The application can then report on this information and becomes a guide for the next step. Manually use the report and compare it with the Informed Consent Master templates (and the Protocol) to be assured of what test(s) can be performed against the samples.
2) Codify the permutations of all the possible outcomes of what test(s) can be completed from the various ICF documents. So that when the report is run from the application the assurances are the same as the first possibility, but with no manual step.
In the implementation of our application we have achieved the first outcome: number 1 above. We can achieve the second possible outcome only when processes that govern the documents (ICF, protocol) are more standardized. Both allow for the same outcome: compliance with the regulations on what test(s) can be performed given I have the appropriate consent.
Associate Director, Clinical R&D IS Business Management & Analytics