Who Volunteers for Clinical Trials? Personality Pathology May Skew the Science

Every clinical trial rests on a quiet assumption that is rarely examined: that the people who agree to take part are, in the relevant scientific sense, ordinary. Researchers design protocols, calculate sample sizes, and randomize participants with great care, yet the very first step of any study, the recruitment of volunteers, happens before any of that machinery can exert control. A new study from Poland suggests that this first step may be quietly reshaping the data that flow from it. In a representative community sample of 1,030 Polish adults, researchers found that people who expressed interest in participating in clinical trials differed systematically from those who did not, and not in trivial ways. Those drawn to trial participation showed lower levels of personality functioning and higher levels of pathological personality traits, along with more depressive symptoms, than their uninterested counterparts.

The study, published in the journal Current Psychology by Anna Włodarska, Anna Zajenkowska, and Izabela Kaźmierczak of VIZJA University in Warsaw, addresses a long-standing methodological worry known as volunteer bias or self-selection bias. Scientific research is vulnerable to both random error, which scatters measurements unpredictably, and systematic error, which pushes them consistently in one direction. Random error can be tamed with larger samples and better instruments. Systematic error is more insidious, because it can masquerade as a genuine finding. If the people who volunteer for studies differ from the population they are meant to represent, then every downstream statistic inherits that distortion, no matter how elegant the analysis.

Volunteer bias has been documented for decades in psychology, where researchers have repeatedly noticed that participants in behavioral studies tend to score differently on personality and affect measures than non-volunteers. Earlier work by some of the same Polish team, published in PLOS ONE in 2023, found that personality and affective disturbances were prevalent among participants in psychological studies, hinting that the problem extended beyond simple demographic skew. The new study extends that logic into clinical research, where the stakes are considerably higher. Clinical trials generate the evidence on which drug approvals, treatment guidelines, and ultimately patient care depend. If trial volunteers carry a distinctive psychological profile, the safety and efficacy data produced by those trials may not generalize cleanly to the broader patient population.

To investigate, the team drew on a representative community sample of Polish adults, a design choice that matters enormously. Most studies of volunteer bias compare actual trial participants with actual non-participants at a single research site, which limits what can be said about the wider population. By surveying a representative cross-section of the community and simply asking respondents about their interest in participating in psychological studies and clinical trials, the researchers could estimate how personality pathology is distributed across the willing and the unwilling in the population at large. Participants completed validated measures, including the Polish adaptations of the Personality Inventory for ICD-11 and the Level of Personality Functioning Scale-Brief Form 2.0, alongside the Patient Health Questionnaire-9 for depressive symptoms.

The theoretical framework underlying the measurement is worth understanding, because it represents a major shift in how psychiatry conceptualizes personality disorder. Both the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the eleventh edition of the International Classification of Diseases have moved toward dimensional models, in which personality pathology is understood as a matter of degree rather than a set of discrete categories. The ICD-11 model assesses two things: a level of personality functioning, which captures how severely a person’s sense of self and relationships are impaired, and a set of pathological trait domains, including negative affectivity, disinhibition, dissociality, and others. This dimensional approach allowed the Polish team to measure personality pathology continuously across their entire sample rather than only in people with formal diagnoses.

The results were striking in their consistency. Individuals who said they were interested in participating in clinical trials showed lower levels of personality functioning, meaning greater impairment in self-organization and interpersonal capacities, than those who were not interested. They also scored higher on negative affectivity, the trait domain encompassing anxiety, emotional lability, and a tendency to experience distressing emotions, and on disinhibition, which reflects impulsivity and difficulty with planning and restraint. Dissociality, a trait involving callousness and disregard for the rights and feelings of others, was likewise elevated. On top of the personality findings, interested respondents reported more depressive symptoms than their uninterested peers, suggesting that mood disturbance and personality pathology travel together in the population of potential volunteers.

Perhaps the most intriguing finding concerned the type of trial. The highest scores on personality pathology and depressive symptoms appeared among respondents interested specifically in psychiatric drug trials. The authors suggest a plausible explanation rooted in perceived benefit: people struggling with psychological distress may see psychiatric drug trials as a route to new treatments and structured care that they might not otherwise access. This creates a paradox with real methodological consequences. The very trials designed to evaluate psychiatric medications may disproportionately attract participants whose personality functioning is impaired, meaning the samples on which psychiatric drug evidence rests could be psychologically distinctive in ways that current screening rarely captures.

Why should this matter for the integrity of trial results? Prior research offers several concrete mechanisms. Psychopathological traits have been shown to influence participant behavior in ways that complicate protocol adherence and data accuracy. Neuroticism, a close cousin of negative affectivity, is associated with larger and more prolonged physiological responses to emotional stimuli, altered cortisol reactivity, and even differences in antibody response to vaccination, all of which could interact with the outcomes a trial is designed to measure. Depressive symptoms can bias decision-making, and personality pathology is linked to poorer treatment outcomes and higher treatment utilization in clinical populations. Participants with elevated disinhibition may struggle with the demands of strict dosing schedules and follow-up visits, while those with high negative affectivity may report side effects differently, skewing safety data in either direction.

The study’s authors argue that their findings highlight the importance of screening trial participants for personality pathology, not to exclude them from research, but to account for their characteristics in the design and analysis of studies. There is a delicate ethical balance here. Volunteers with psychological distress are precisely the people who may benefit most from access to experimental treatments, and excluding them wholesale would be both unfair and scientifically wasteful. But ignoring the pattern risks a subtler form of harm: trial results that look generalizable but are actually calibrated to a psychologically atypical subset of the population, with safety profiles and efficacy estimates that may not transfer to typical patients.

The research, which was part of a larger project on hostile attribution and was approved by the Maria Grzegorzewska University Research Ethics Committee, adds a compelling new dimension to an old methodological conversation. It suggests that the gate through which every participant passes, the decision to volunteer, is itself psychologically patterned, and that the pattern runs toward pathology rather than away from it. For a field that has invested enormously in randomization, blinding, and statistical rigor, the message is humbling: some of the most consequential selection into the evidence base happens before a single protocol procedure begins. As clinical science grapples with replication problems and questions about generalizability, understanding who volunteers, and why, may prove to be one of the most underappreciated levers for improving the reliability of medicine itself.

Subject of Research: Volunteer bias in clinical trials linked to personality pathology and depressive symptoms

Article Title: Personality pathology and willingness to participate in psychological and clinical trials

Article References: Włodarska, A., Zajenkowska, A., & Kaźmierczak, I. (2026). Personality pathology and willingness to participate in psychological and clinical trials. Current Psychology, 45(19), Article 1566. https://doi.org/10.1007/s12144-026-10067-y

Image Credits: AI Generated

DOI: 10.1007/s12144-026-10067-y

Keywords: volunteer bias, selection bias, personality pathology, clinical trials, depressive symptoms, ICD-11, negative affectivity, disinhibition, psychiatric drug trials, research methodology, personality functioning, self-selection