Could fingerprints play a role in drug trials of the future? A forensic scientist’s perspective
Although readers of Drug Target Review may be more focused upstream of clinical trials in the drug discovery pipeline, the efficacy of clinical trials should also be of interest. Millions of pounds invested in drug discovery in the laboratory could easily go to waste if the clinical trials stage is not carried out effectively.
It is well known that adherence to medications in clinical trials is low, and this has a real impact on their efficacy at evaluating the true benefit of a newly discovered drug. Non-adherence can occur for various reasons, such as patients not reporting non-adherence for fear of upsetting clinicians, a misunderstanding of dosing requirements or patients being too busy to remember to take their medications.1 The effect of poor adherence means that clinical trials are forced to over-recruit to gain statistically significant data. For example, a non-adherence rate of 40% would require a 200% increase in sample size. This results in not only increased cost of clinical trials but also a poor understanding of the efficacy of a medication. A medication will not appear to be anything like as effective as it could be if only half of the patients are taking it! So how can a simple fingerprint help to improve the situation?
Fingerprints have contributed crucial information to police investigations for the past 150 years and have helped to solve countless crimes around the globe. But researchers, such as myself and my team at the University of Surrey, are beginning to unravel the many things that a fingerprint can be used for outside of the crime scene.
A fingerprint consists of substances that a person has touched, as well as biomolecules that are excreted from the eccrine glands. Police authorities use various reagents to enhance fingerprints, which are unique to an individual. These reagents interact with the chemicals deposited in the fingerprint material in order to produce visible contrast. However, there are some surfaces on which it can still be very difficult to develop fingerprints, and therefore obtaining a more detailed understanding of the interaction between fingerprint, the surface it is being deposited on and the environment in which it is aged is a key research area in forensics. It is through exploring the chemistry of a fingerprint that researchers have started to realise that a fingerprint can be used for more than just its ridge detail.
Fingerprints at crime scenes are generally known as ‘fingermarks’ – where the fingerprint is deposited under uncontrolled conditions by an unknown donor. Fingermarks are known to be highly heterogeneous in composition, which causes an enormous problem for forensic providers trying to develop them. However, by giving a fingerprint under controlled conditions (an elective fingerprint), it is possible to reduce this variability. For example, by washing a finger before depositing an elective fingerprint, it is possible to obtain a sample of eccrine sweat, reducing the effect of environmental contaminants. Substances from eccrine sweat previously found in fingerprints include amino acids, salts, urea as well as peptides and small proteins. In addition to this, researchers in our group, as well as in other laboratories have detected prescription medications as well as illicit drugs in fingerprints.
In drug testing, a fingerprint offers an attractive sample matrix, because they are easy to collect and the identity of the donor is embedded in the sample, which assures traceability. Fingerprint-based drug testing emerged recently from the University of East Anglia and has become the key business of Intelligent Fingerprinting Limited, who have developed an immunoassay test for drugs of abuse from a fingerprint. An obvious challenge to the efficacy of fingerprints for drug testing is the possibility of accidental environmental contamination, but recent research that we have published in Clinical Chemistry 2,3 shows that although cocaine (a common environmental contaminant) and its metabolite can be detected in the fingerprints of non-drug users, the levels observed in drug users are considerably higher, and it is, therefore, possible to establish a cut-off to avoid false positives.
A fingerprint, therefore, also offers a new opportunity for monitoring whether a patient has successfully taken and absorbed medication in a clinical trial. A fingerprint test is robust enough to demonstrate that a drug has been ingested and metabolised, and is applicable to therapeutic doses of a medication as well as the high doses taken by drug users. Because fingerprints are easy to collect, store and transport, they open up a unique opportunity for testing patients from their own homes. We have recently developed a method for time stamping a fingerprint, so the fingerprint will specify who gave the sample, what they took and when it was deposited. The sample could be transported in a simple collection cartridge, transported to an analysing laboratory and rapidly analysed, thus confirming that a drug is effectively metabolised (and taken in the first place).
Clinical trials, of course, require a different testing paradigm to drug testing, where (unlike in drug testing) a good outcome for a patient is to show that they have taken a medication. Because metabolites of the drug are excreted alongside the various other endogenous compounds present in a fingerprint, it may be possible to also mine information about how a drug is being metabolised and to spot any previously undiagnosed problems, like malabsorption of the drug.
There are various alternative approaches to combatting adherence in clinical trials, including text message, pill counting and video monitoring, but none of these approaches can show that a medication has been taken, absorbed and metabolised. There are many other approaches that can be used to monitor drugs in biofluids, but none offers the ease of collection, transportation and traceability that a fingerprint sample can offer.
Of course, there are many reasons why adherence in clinical trials is poor. Monitoring patients from a fingerprint will not solve all of these problems, and it may well introduce its own problems. What if the collection of fingerprints makes patients feel they are being spied on? What if the pharma industry does not want to take the risk of initially increasing the cost of their clinical trials before they see a benefit? But monitoring from a fingerprint does present some significant new opportunities. Fingerprints contain thousands of biomolecules and mass spectrometry approaches collect all these simultaneously along with the drug. These could be mined to explore the interplay of the drug with other key biomarkers in the body. Additionally, because non-adherence often varies over time (patients do not necessarily avoid taking their medication but may sometimes miss doses or underdose), monitoring gives clinicians the opportunity to exclude results from patients who have not managed to comply with their treatment regimes when determining the efficacy of a new treatment.
- DOI: 10.1373/clinchem.2017.275578
- DOI: 10.1373/clinchem.2017.281469
MELANIE BAILEY is a lecturer in Forensic Analysis from the University of Surrey. She has worked alongside various law enforcement agencies to develop new techniques to image fingerprints and has been exploring the chemical composition of fingerprints for the past 10 years. She is an expert consultant of the international atomic energy agency and Chief Analyst at the Surrey Ion Beam Centre. Twitter: @drmelbailey.