Genetic testing for PD is more accessible than ever before through research studies like PD GENE, direct-to-consumer testing, and traditional clinical settings with a physician or genetic counselor14. However, there is the potential for discrepancy between perceived utility by providers and what PwP may actually experience with such testing, which has not been explored in depth by researchers. This study aimed to address this gap in the literature by investigating the personal utility reported by PwP who underwent genetic testing for PD in the context of a research study. Additionally, we investigated the impact of genetic testing on life changes and enrollment in additional research studies, including gene-specific clinical trials. Importantly, 80% of participants found some personal utility in their genetic test results, regardless of whether results were positive or negative. In addition, 45% of participants were interested in participating in additional research studies, and 16% of participants actually enrolled in another study.
Most participants found genetic testing for PD to be personally useful in multiple ways. Greater than 75% of participants reported that their genetic test results were useful for satisfying their curiosity, making them feel good about helping the medical community, providing information, and having information to share with family members. There were no significant differences between the proportion of PwP with positive results and PwP with negative results who found their genetic testing results useful for any aspect of personal utility. Multiple prior studies have demonstrated that PwP and their family members are interested in genetic testing for many reasons, including medical management, informing family members risks, or financial planning10,11. Our study adds to this knowledge by demonstrating that most people who receive genetic testing for PD do find personal utility in their test results, even when clinical utility is limited. Participants who found their genetic test results to be useful for informing plans for school or career, informing decisions about having children, and helping them cope with their health risks were significantly younger on average than participants who reported that genetic testing was not personally useful. This data suggests that some elements of personal utility provided by genetic testing, such as reproductive decision-making and career planning, may be more valuable for younger individuals.
Most participants with negative genetic test results report finding genetic testing useful in multiple ways, despite not receiving an explanation for why they developed PD. Prior research reported that people with negative genetic test results find comfort in their results while still understanding that other factors can contribute to disease risk15. This is supported by the open-text responses provided by some gene negative participants who reported feeling relieved after receiving their negative genetic test results. Additionally, 80% of participants with negative results endorsed feeling good about helping the medical community by participating in the study, an example of participant-reported research altruism. Prior research has found altruism to be a common motivation for participation in research, particularly in combination with a perceived benefit to participation such as learning health information16,17.
One of the aims of our study was to assess the clinical trial interest and enrollment behavior of participants after genetic testing. We hypothesized that identifying PwP with positive genetic results would lead to enrollment in gene-specific clinical trials. One-third of participants with positive results reported interest in participating in a PD research study due to their positive genetic test; however less than a third of those participants had enrolled in another PD study. Participants were not required to write-in the name of a clinical trial they had enrolled in or were interested in, but of those who did, three participants mentioned gene-specific clinical trials. We are aware of at least six gene-specific clinical trials for LRRK2 and GBA1 in the United States that had overlapping enrollment periods to this study, including observational and interventional trials (NCT03545425, NCT04668898, NCT04101968, NCT03234478, NCT02906020, NCT04127578). However, at the time of recruitment there were no phase 2 clinical trials for either LRRK2 or GBA1. There are many reasons why participants may not enroll in additional research studies including various accessibility issues, a high participant burden, risk aversion to interventions that may cause side effects, the possibility of getting a placebo, or not meeting study inclusion criteria18,19. At the time of survey completion, only 30% of participants had shared their genetic test results with a provider. Conversations with a healthcare provider about additional research participation perhaps had not taken place for participants who may have later enrolled in additional research after completing the survey. We highlight that the lack of large clinical trials for PD-related genes at the time could have played a role in trial enrollment. Additionally, enrolling participants with positive genetic results in gene-specific trials presents a challenge. The ideal trial participant may be a recently diagnosed individual who may not be compelled to enroll at the time because they perceive their symptoms to be manageable or are still processing receiving a new diagnosis20. For gene-specific clinical trials to enroll enough participants, PwP with genetic forms of PD will need to be identified through genetic testing; however, an important takeaway from this study is that simply identifying those with a genetic variant linked to PD may not be enough to lead to clinical trial enrollment for various reasons.
Clinical trials are rapidly evolving, with new trials emerging frequently such that it is not realistic to expect clinicians to be familiar with every clinical trial that could be an option for every patient. However, providers are an important point of contact for patients as research has shown that most clinical trial participants discuss enrollment with their healthcare provider21. A 2020 survey of physicians and nurses found that while over 80% of physicians feel comfortable providing information and discussing clinical trials with their patients, time constraints in appointments, difficulty accessing information about clinical trials, and a lack of time to evaluate clinical trials serve as major barriers to referral21. Less research is available about the behavior of genetic counselors when discussing clinical trials with their patients; however, providing education about research is highlighted as a critical role of genetic counselors in the National Society of Genetic Counselors’ most recent definition of genetic counseling22. Informing patients of relevant clinical trials is clearly within the scope of practice of both physicians and genetic counselors. Our study suggests that patients are interested in participating in research but may need to be encouraged to share test results with their healthcare providers and may need guidance in next steps, such as assistance with finding and enrolling in studies. There are useful resources that can be shared with patients considering participation in clinical trials, including study search tools like ClinicalTrials.gov (www.clinicaltrials.gov) and the Fox Trial Finder (www.michaeljfox.org/trial-finder) and patient-facing materials available on foundation websites (www.parkinson.org/library/fact-sheets/research; www.michaeljfox.org/your-role-research. A detailed patient-facing digital guide to clinical trials is also available: https://www.michaeljfox.org/sites/default/files/media/document/PDEC_Patient_Guide_Digital_12.11.20_1.pdf). Of note, participants with both positive and negative results were interested in participating in PD research studies, highlighting the importance of assessing PwP’s interest in research regardless of test results.
Of those who had experienced change since receiving genetic test results, the most common was a medical event or medication adjustment. Life changes such as changes in relationship status or career changes were reported among both genetic test result groups as well as lifestyle changes including changes to diet and exercise habits. Two participants, both with positive test results, reported negative psychosocial reactions. One participant expressed concern over how the result would affect their family, while the other reported increased anxiety over having an additional disease. This is consistent with prior research demonstrating that although most PwP do not experience negative feelings after genetic testing, some individuals with positive results may have negative psychological reactions23. This finding highlights the importance of providing genetic counseling that includes anticipatory guidance to help patients prepare for and navigate complex emotions when they receive genetic test results.
Our study contains both strengths and limitations. A major strength of our study is the large sample size. However, our sample population is demographically homogenous with overrepresentation of White and college-educated individuals. This could limit the generalizability of our findings to other populations. The study hopes to survey PwP living outside the U.S. as the PD GENE study expands, collaborating with other research groups including the Global Parkinson’s Genetics Program (GP2; https://gp2.org/about-gp2/) and the Latin American Research consortium on the GEnetics of Parkinson's disease (LARGE-PD; https://large-pd.org/). Additionally, selection bias may have impacted our results as our participants must have some interest in research as they are already participants in the PD GENE study, which may have led us to an overestimate of the interest in research participation. The survey design with its structured data format could also limit ascertaining the breadth of participant experiences, which is likely to be heterogeneous; although, the addition of open text boxes allows for some free responses. Comparisons of personal utility items were not performed on genetic subgroups as counts were too small. Some participants received results from their own neurologist, which may have led to an underestimation of the participants who shared results with a healthcare provider; these participants may have responded they did not share results with their provider, perceiving it as unnecessary because their provider already knew their results. The timing of the survey may not have captured those who enrolled in additional research later or participants who discussed genetic test results with a healthcare provider after survey completion. Not sharing test results with health care providers could have skewed some of the clinical trial responses to the questions regarding enrollment, since physician input likely plays a role in decision-making. Lack of large clinical trials at the time of the study may also have played a role in enrollment numbers. Additionally, the COVID-19 pandemic may have had an effect on participants’ enrollment or interest in additional clinical trials. Importantly, most participants had negative genetic test results, which could have resulted in less interest in clinical trials and personal utility responses, although we observed that result type did not always align with expected responses.
Future research could focus on identification of modifiable factors that increase or reduce participants’ interest in future clinical trials. In addition, it will be important to investigate perceptions of personal utility among individuals with PD from other population groups. In the future, we plan to study the personal utility of genetic testing in PwP using qualitative methods. Reassessing clinical trial interest and enrollment will be important, as large gene-targeted trials such as ACTIVATE by Bial R&D (NCT05819359), LIGHTHOUSE, now LUMA, by Biogen (NCT05418673, NCT05348785), and PROPEL by Prevail Therapeutics (NCT04127578) and others continue to emerge.
In conclusion, we observed that most participants find personal utility in their PD genetic test results in multiple ways, including satisfying their curiosity, contributing to the “greater good” in medical research, and providing information to family members, with younger participants endorsing certain items more frequently (i.e. career planning, family planning). For most participants, genetic test results did not lead to medical or life changes. We observed that many research participants are interested in participating in other studies, but may not enroll. This requires further exploration as to why PwP may not be enrolling in studies and suggests that physicians and genetic counselors should act as facilitators when there is expressed interest. While it may not be realistic for clinicians to be familiar with every emerging trial, clinical providers are an important point of contact to aid and provide resources for patients and their families who are interested in research.