by James Rudge, PhD, Technical Director, Neoteryx | 6 min read
A “Letter to the Editor” by Christophe P. Stove et al at Ghent University, Belgium, in the April 2021 issue of Clinical Chemistry and Laboratory Medicine (CCLM), reported on a large at-home study using Mitra® devices with VAMS® technology for remote specimen collection to monitor abstinence of alcohol consumption during a ‘dry February’ abstinence initiative. The letter is entitled “Self-sampling at home using volumetric absorptive microsampling: coupling analytical evaluation to volunteers’ perception in the context of a large-scale study.” The letter describes successful recruitment, remote blood sample collection and testing of 796 volunteers to measure the alcohol use biomarker phosphatidylethanol (PEth). The letter concluded that due to the high quality of the samples obtained from Mitra devices with VAMS the results of this large-scale and remotely executed study supported the feasibility of patient-centric home-sampling by non-experienced volunteers. A follow-up paper on the same study published in January 2022 concluded that PEth was “useful to monitor short- to mid-term cessation of alcohol consumption.”
Background on Alcohol Consumption & Overuse
The World Health Organization (WHO) reports that 3 million deaths occur worldwide every year from the “overuse” or harmful use of alcohol. The WHO also reports that harmful use of alcohol is a causal factor in injuries and diseases. Statistics show that 5.1% of the global burden of disease and injury is attributable to alcohol use or overuse, which negatively impacts not only the drinker, but those around them.
Over consumption of alcohol is a major concern for healthcare systems and governments. Concern has heightened in the past two years after a report from the National Center for Drug Abuse Statistics (NCDAS) revealed that people in the United States (US) increased their alcohol consumption by 60% during COVID-19 lockdowns.
Much research has been conducted on the damage that alcohol overuse and chronic alcohol consumption has on individuals, families, and society. A recent paper in the journal Hepatology stated that alcohol-related liver disease (ALD) in the US accounts for more than $5 billion in direct health costs and, in the last decade, ALD mortality has increased by 200% in 25–34-year-olds. It is predicted that over the next decade 260,000 Americans will die as a result of ALD.
Monitoring Alcohol Overuse
From law enforcement and traffic control to teen health interventions, child custody cases, addiction rehabilitation, and medical toxicity concerns, monitoring alcohol consumption and abstinence are of critical importance. However, precise and effective alcohol monitoring has always been a challenge.
There are several alcohol biomarkers, such as ETG and CDT, which can be used to monitor alcohol use a few hours or even days after consumption. However, due to its short half-life, a metabolite of ethanol, (ethyl glucuronide (EtG)), needs to be monitored twice weekly. On the other hand, carbohydrate deficient transferrin (CDT) has a longer half-life (15 days), but it is reported to show low sensitivity (77%) and specificity (88%). In recent years, the biomarker phosphatidylethanol (PEth) has become a popular choice for alcohol monitoring, as it has shown to have an improved half-life of ~7-8 days compared to ETG with higher sensitivity (95%) and specificity (100%) compared to CDT.
Analyzing PEth in Dried Blood Samples
PEth forms when alcohol reacts with membrane phospholipase in blood cells and so it can be measured with a whole blood test. The assay also lends itself to a dried blood analysis. Indeed, the group led by Christophe Stove, had previously fully validated an LC-MS/MS method for measuring PEth from dried blood samples collected on Mitra devices with VAMS. The stability of the biomarker was found to be 1 month at 4° C, RT and 45° C. Furthermore, a long-term study of PEth showed that the VAMS samples were stable for at least 400 days at RT, making volumetric absorptive microsampling with the Mitra device an ideal candidate for remote sampling in PEth studies.
The research group at Ghent University determined that large studies utilizing high-quality VAMS samples self-collected by study participants at home were lacking in the literature and felt that remote specimen collection with VAMS may be an unknown resource in the industry. They conducted this large-scale study, in part, to address this gap in the literature. They used the alcohol abuse marker PEth, specifically 16:0/18:1 (palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol), as a predicate to also gain critical data on whether PEth could be reliably measured from samples collected at home by study volunteers.
Sample Extraction Study Methods & Findings
The study recruited 796 volunteers online, where kits (assembled by the investigators) containing Mitra devices were sent for home collection. Kits also included clear instructions (written and video) produced by the group.
Samples were collected at 3 timepoints (2-week intervals) throughout the month of elected abstinence (‘Tournée Minérale’ initiative), similar to other events such as ‘Dry January’).
A high percentage of the cohort (86.3%) completed the study.
Cohort ages ranged from 18-60 years, with a slightly higher bias observed towards females (63%).
Less than 5% of the cohort needed to request additional kits or required additional lancets.
Of the kits that were returned, the device tips were inspected for evidence of over or under sampling prior to testing. At each time point, 91-93% sampling success rate was observed.
Around 83% of volunteers were able to provide samples of acceptable quality for all three timepoints.
In terms of sampling imprecision:
14% imprecision was observed compared to controlled sampling (11%).
Statistical analysis of the data showed that sampling imprecision accounted for 9% of the method; the authors concluded that “overall imprecision was deemed acceptable, when applying international guidelines on incurred sample reanalysis and considering the in-house allowed expanded measurement uncertainty (k=2, 38%) for PEth.”
The volunteers were also surveyed on their views on home sampling:
A high proportion of the participants (n=501, 73%) completed the survey.
Most of the responders had never conducted a fingerpick (77%).
The majority judged the instructions (prepared by the investigators) to be good or very good.
The participants scored the pain of sampling as less than four out of ten.
The investigators commented that almost “80% would prefer this type of sampling over a conventional blood draw by trained personnel, if needed on a monthly basis.” This preference for capillary sampling was also reported on in a previous VAMS study also headed up by Christophe Stove (measuring HbA1c) and reported that only 16% of a cohort preferred traditional blood sampling and furthermore that VAMS was a preferred technique compared to DBS. Indeed, they stated, “VAMS clearly stood out, in both adults and children.” Finally, a separate VAMS study by the Mayo clinic 2020 also reported that 82% of an n= 100 cohort of transplant patient preferred self-collection and 73% of a cohort of 48 reported that capillary sampling was less painful than venous sampling.
Drawbacks of the study:
A high portion of the cohort were well educated, and this could have had a positive influence on the success and the quality of the sample collection.
The study used the Tournée Minérale initiative to recruit the volunteers so they may have been more motivated towards success of the project.
Study Authors’ Conclusions
The study supports the feasibility of home sampling by the layperson
The success of the study was in part due to good quality samples obtained; this was attributed to the participants being intrinsically motivated.
Final Thoughts & Comments
The study by the authors demonstrated that when executed well, very high-quality data can be achieved from samples collected by laypeople at home. The volunteers’ preference for capillary sampling in this study was also reported in a previous VAMS study headed up by Christophe Stove (measuring HbA1c). That earlier study reported that only 16% of a cohort preferred traditional venous blood sampling and it was reported that VAMS was a preferred technique compared to DBS. Indeed, for that earlier study the investigators stated, “VAMS clearly stood out, in both adults and children.”
Finally, a separate VAMS study by the Mayo Clinic in 2020 also reported that 82% of an n= 100 cohort of transplant patient preferred self-collection and 73% of a cohort of 48 reported that capillary sampling was less painful than venous sampling. Indeed, a recent follow up paper published by the same group statistically analyzed the data and concluded the following:
The half-life of PEth was 7.9 days which was in line with other observations.
In terms of scoring compatibility with abstinence, looking at the relation between two consecutive PEth values they were able to yield a sensitivity / specificity score of 89%, which “offers an added-value compared to other well-established procedures assessing biomarkers for ethanol intake.”
The approach was “useful to monitor short- to mid-term cessation of alcohol consumption.”
This study paper was summarized for our readers by James Rudge, PhD, Neoteryx Technical Director. This is curated content. To learn more about the important research outlined in this review, visit the original "Letter to the Editor" published in the journal, Clinical Chemistry and Laboratory Medicine (CCLM).