Anesthesia Providers as Stakeholders to Adoption of Pharmacogenomic Information in Perioperative Care

Abstract

Objectives:

Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care, and pain medicine providers would uncover unique considerations for future implementation within perioperative care.

Methods:

A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program. The survey addressed knowledge, perceptions, experiences, resources, and barriers.

Results:

Of 153 providers contacted, 149 (97%) completed the survey. Almost all providers (92%) said that genetic results influence drug therapy, and few (22%) were skeptical about the usefulness of pharmacogenomics. Despite this enthusiasm, 87% said their awareness about pharmacogenomic information is lacking. Feeling well-informed about pharmacogenomics was directly related to years in practice/experience: only 38% of trainees reported being well-informed, compared to 46% of those with 1–10 years of experience, and nearly two-thirds with 11+ years (p<0.05). Regarding barriers, providers reported uncertainty about availability of testing, turnaround time, and whether testing is worth financial costs.

Conclusions:

Anesthesiology, critical care, and pain medicine providers are optimistic about the potential clinical utility of pharmacogenomics, but are uncertain about practical aspects of testing and desire clear guidelines on use of results. These findings may inform future institutional efforts toward greater integration of genomic results to improve medication-related outcomes.

INTRODUCTION

Pharmacogenomics, the study of how genetic variations affect interindividual variability in responses to medications, is increasingly being incorporated into clinical workflows at many institutions in hopes of achieving more personalized care. Currently, the U.S. Food and Drug Administration (FDA) acknowledges the potential importance of pharmacogenomic information to inform prescribing and includes pharmacogenomic information in drug labels for many medications.[1] International organizations exist to provide evidence-based guidelines and resources to assist clinical implementation efforts, such as the Clinical Pharmacogenetics Implementation Consortium (CPIC)[2], PharmGKB[3], and the Dutch Pharmacogenetics Working Group (DPWG)[4]. With advances in biomedical technology, pharmacogenetic testing has also become progressively more affordable and widespread. Altogether, these have led to broad implementation efforts in multiple clinical settings.[5,6]

However, despite initial enthusiasm about the potential for using genetics to guide medication prescribing and improve outcomes, pharmacogenomic implementation requires overcoming many barriers in order to achieve eventual measurement of clinically meaningful outcomes.[7–12] Providers are key stakeholders in these implementations, but often lack sufficient knowledge and confidence in applying genetic information to clinical decision making. This represents a significant barrier to adoption of pharmacogenomic information.[9] Adoption of pharmacogenomic information into routine clinical care has therefore lagged in many clinical settings.[13,14]

One of the most important challenges is understanding the readiness of clinicians to adopt pharmacogenomic information in the context of their current workflows, which are often over-burdened, and sometimes constrained, by existing healthcare delivery models. Performing assessments of provider knowledge of and attitudes towards pharmacogenomics is therefore essential. Perceptions of different types of providers have been previously explored in various clinical settings.[14–24] However, literature assessing the perceived clinical utility of pharmacogenomic information among anesthesiologists, critical care, and pain medicine providers is relatively sparse[25], despite the fact that pharmacogenomic information could be highly useful in this high-risk setting.

In this study, we used a survey tool to assess perioperative providers’ attitudes, experiences, and understanding of pharmacogenomics with the aim of identifying unique barriers to adoption in this distinctive group. We hypothesized that understanding baseline attitudes and perceptions of these providers would uncover unique considerations for implementation in the perioperative care setting.

PARTICIPANTS AND METHODS

Ethical approval for this study (IRB17–1422) was provided by the University of Chicago Institutional Review Board (IRB), Chicago, IL on April 25, 2018. The trial was registered at clinicaltrials.gov (NCT03729180, Principal Investigator: Peter H. O’Donnell, Date of registration: November 2, 2018), and written informed consent was obtained from all provider-subjects and patient-subjects.

The ImPreSS Trial is a single-center, prospective, randomized controlled study to examine the feasibility and utility of implementing pharmacogenomic decision support in the perioperative care setting. The full trial has been previously described in detail elsewhere.[26] Briefly, the study consists of an initial run-in period wherein patients enrolled in the first 6 months had clinically relevant pharmacogenomic markers preemptively tested prior to surgery with results delivered to the treating Anesthesia care team prior to the day of surgery. The purpose of the run-in period was for process evaluation and refinement. The run-in phase was followed by the randomized phase where patients are randomized in a 1:1 fashion to either the pharmacogenomic arm (n=900 patients) with upfront pharmacogenomic testing and delivery of results to the anesthesia team prior to (and during and after) the surgery, or the control arm (n=900 patients) where upfront pharmacogenomic testing is not performed (usual care). Participating providers completed a longitudinal survey at baseline (at the beginning of the run-in period, before treating their first study patient), and will complete the same survey every 6 months for the duration of the trial to assess attitudes, experiences, and understanding of pharmacogenomics over time.

Participants

Providers from the Department of Anesthesia and Critical Care (DACC) at the University of Chicago, including faculty physicians (MD-F), house-staff physicians (MD-H; including residents and fellows), certified registered nurse anesthetists (CRNA) and advanced practice nurses (APN), and intensive care unit (ICU) pharmacists (PharmD) were eligible for participation in the ImPreSS Trial. We engaged providers through a process of stakeholder engagement by presenting at departmental and other clinical specialist group meetings to share the concept for a pharmacogenomics implementation study in the perioperative care setting. Providers consented to collection of survey responses at baseline and every 6 months for the duration of the ImPreSS Trial, as well as passive tracking of medication prescribing/administrations during the care of enrolled patients.

Development of Surveys

The longitudinal survey instrument (Appendix A) was designed to assess key constructs of an implementation and dissemination model that combined elements of Self-Regulation Theory of Health Behavior[27,28] and Rogers’ Diffusion of Innovation Theory[29]. Key constructs include physician awareness/understanding of the topic (pharmacogenomics), education/opportunities for learning about the topic, attitudes/perceptions about genomics and pharmacogenomics, perceived attributes and limitations of genomic information and using genomic information at the point-of-care (compatibility, complexity, trialability, relative advantage), attitudes regarding adoption of new clinical practices, medication outcome expectancy, features of the institutional learning climate, peer behaviors, and patient influences.

These themes were identified through extensive literature review and from discussion topics at several national meetings, and the final themes were narrowed and chosen with assistance of members of The University of Chicago Survey Lab and Center for Health and the Social Sciences (including D.O.M. and P.H.O.) and include those illuminated by our prior pharmacogenomics implementation projects.[30–33] The large majority of the items in the final survey were contained within our previously-developed and published instrument, already tested in >200 providers from our other studies.[9,30] Wording of several questions was updated for relevance to the perioperative prescribing setting. The final instrument consisted of 37 multiple choice and Likert-scale questions. Administration of the survey to all participating providers was part of the pre-specified procedures for the ImPreSS Trial and all consenting providers agreed to being regularly surveyed.

Collection of survey responses

Surveys were distributed, completed and returned between June 2019 and March 2020. Each of the participants was invited by email to participate in the on-line survey with a unique link. Study data were collected and managed using REDCap (Research Electronic Data Capture), a secure, web-based application designed to support data capture for research studies, hosted at the University of Chicago.[34] Responses from all survey respondents were anonymized to ensure confidentiality and all collected data were de-identified prior to analysis. Following the initial invitation, up to two additional reminders were sent to each participant after approximately 3–4 weeks. Those not captured through the above mechanisms were approached by a member of the study team, and the surveys were administered in-person and collected using either REDCap or on paper. Paper surveys were then manually entered into REDCap.

Statistical Analyses

The purpose of analyzing the baseline survey as a unique time point was to determine perceived perceptions and barriers to adoption and implementation in this setting, prior to receipt of any genetic information. The primary outcomes were 1) to assess providers’ attitudes, experiences, and understanding of pharmacogenomics at baseline; 2) to determine differences in responses between provider types; and 3) to determine differences in responses between providers stratified by years of experience.

Individual surveys were included in the final analysis if the majority of questions were completed. Individual questions that were left blank were excluded from analysis of that item. Descriptive statistics were used to present survey responses. For multiple-choice questions, data were reported as a percentage of responses. For Likert-scale questions, “strongly agree” and “somewhat agree” were combined and compared with combined responses from those who reported “somewhat disagree” and “strongly disagree”, compared to “not sure”. For each question, the responses were first compared overall across all four provider types using Fisher’s exact test. If the overall p-value was statistically significant, pairwise comparisons were performed to assess which individual provider group(s) were significantly different from other provider groups. If the overall p-value was not significant, no further comparisons were formed. A nominal p value of < 0.05 was considered statistically significant, and was not adjusted for multiple testing.

RESULTS

Provider descriptive characteristics and response rates

Of 153 providers contacted, 149 returned the surveys (97%). Of these 149 included in the final analysis, 132 respondents answered all items, and only 17 (11%) had 1–3 questions left blank (surveys with >3 items unanswered were excluded from analysis). Provider summary statistics and survey response rates are summarized in Table 1.

Table 1.

Department of Anesthesia and Critical Care provider survey response rates and average years in practice.

Provider Type	Surveys Sent	Surveys Completed	Response Rate (%)
MD-F	55	55	100.0%
MD-H	61	60	98.4%
CRNA and APN	30	27	90.0%
PharmD	7	7	100.0%
Total	153	149	97.4%

Years in Practice
Provider Type	0	1–10	11 or more	Average (range)a
MD-F	4	25	26	11.5 (0–30)
MD-H	60	0	0	N/A
CRNA/APN	0	21	6	8.8 (1–32)
PharmD	0	6	1	6.7 (4–13)
Total	64	52	33	10.3

The average years of experience for the entire group was 10.3 years. Most providers with 11 or more years of experience consisted of MD-F (26 out of 33). MD-F: faculty physicians; MD-H: housetaff physicians, including residents and fellows; CRNA: certified registered nurse anesthetists; APN: advanced practice nurse; PharmD: pharmacists.

^aAverage years in practice post-training. MD-H, including residents and fellows, were excluded from average years in practice calculation, since by definition their value was “zero”.

Survey domains and themes

Responses to questions within each domain and emerging themes are discussed in detail below.

Support, resources, and guidelines for adopting genomics in clinical practice

Questions regarding institutional support, resources, and guidelines for adopting clinical practices are summarized in Table 2 and themes discussed in detail below.

Table 2:

Questions regarding institutional support, resources, and guidelines for adopting genomics in clinical practice

	Disagree Strongly	Disagree Somewhat	Not Sure	Agree Somewhat	Agree Strongly
My institution encourages exploring novel innovations/tools for use in clinical practice.	0%	0%	5%	40%	54%
My department promotes the integration of new knowledge into clinical decision-making.	0%	1%	4%	32%	63%
I feel pressured to conform to institutional or national practice pattern guidelines in my clinical decision-making.	13%	16%	34%	29%	8%
In some circumstances, I adopt clinical practices despite the lack of formal guidelines.	4%	9%	19%	53%	15%
I feel uncomfortable adopting new clinical tools unless my peers and/or my medical specialty have adopted/endorsed it first.	9%	34%	23%	32%	4%
I generally have adequate nursing and ancillary staff to support my clinical practice.	1%	7%	16%	50%	25%
I have adequate time and institutional resources dedicated to clinical research efforts.	7%	23%	36%	26%	9%
My institution’s EMR adapts to incorporate new clinical practices/tools/decision support.	1%	11%	21%	48%	19%
Improving patient safety through the promotion/adoption of enhanced clinical practice tools is a goal of my institution.	0%	2%	10%	42%	46%
I feel that my institution supports/champions the adoption of PGx.	1%	3%	26%	50%	20%

EMR = Electronic medical records; PGx = pharmacogenomics

Almost all providers felt encouraged to explore novel innovations/tools for use in clinical practice, and felt their practice setting promotes the integration of new knowledge into clinical decision-making (94% and 95%, respectively). Additionally, the vast majority (88%) said improving patient safety through the promotion/adoption of enhanced clinical practice tools is a goal of their practice.

Although some providers reported feeling pressured to conform to local or national practice pattern guidelines in their clinical decision-making and some reported feeling uncomfortable adopting new clinical tools unless their peers and/or medical specialty have adopted/endorsed it first, many would still adopt clinical practices despite the lack of formal guidelines. Notably, more MD-F and PharmDs would adopt clinical practices despite the lack of formal guidelines (84% and 86%, respectively), compared to MD-H and CRNA/APN (57% and 56%, respectively, p<0.05 comparing MD-F to MD-H and CRNA/APN).

Finally, integration of pharmacogenomic information into the electronic medical record (EMR) was identified as a priority, alongside a desire for clear guidelines for adoption. Two-thirds (67%) of providers reported that their EMR adapts to incorporate new clinical practices/tools/decision support, however very few (15%) said that pharmacogenomic information is well-integrated into the institutional EMR. Furthermore, very few (9%) thought there are clear guidelines for how pharmacogenomics information should be used and almost half of all providers were unsure whether clear guidelines even existed.

Understanding of pharmacogenomics

A majority of providers said their awareness about pharmacogenomic information is lacking, with MD-H having the highest rate of such responses (95%), compared to 72–85% in all other provider types (p<0.05, comparing MD-H to MD-F). Possibly related to this finding, a similarly large number of providers thought that the study of pharmacogenomics should be included in formal medical training. About half said they felt somewhat or very under-informed about pharmacogenomics while very few (4%) said they felt very well-informed (Figure 1a). Interestingly, with an increasing number of years of practice, providers felt increasingly more informed about pharmacogenomics (Figure 1b). While approximately half of all providers were unsure about whether there is sufficient pharmacogenomic information for most drugs, the majority thought less than 40% of medications they commonly prescribe/administer have had clinical studies performed exploring pharmacogenomic information about them. Many providers (73%) were likewise unsure whether the laws for protection of patient genetic information are adequate.

Figure 1. Perceptions of degree to which providers feel informed about pharmacogenomics.

Shown are responses to the question “How informed do you feel about pharmacogenomics?” stratified by provider types (top panel) and years of experience (bottom panel). Very few providers felt very well-informed, regardless of provider type or years in practice, and the majority felt somewhat or very under-informed. With increasing number of years of practice, providers felt increasingly more informed about pharmacogenomics. MD-F: faculty physicians, MD-H: housestaff physicians, including fellows and residents. CRNA: certified registered nurse anesthetists. PharmD: pharmacists.

Provider-perceived clinical utility of pharmacogenomics

Select questions regarding provider-perceived utility of pharmacogenomics are outlined in Table 3, and themes are discussed in detail below.

Table 3:

Questions regarding provider-perceived clinical utility of pharmacogenomics

	Disagree Strongly	Disagree Somewhat	Not Sure	Agree Somewhat	Agree Strongly
I am skeptical about the usefulness of PGx.	12%	39%	27%	20%	2%
Patients are skeptical about the usefulness of PGx.	1%	13%	73%	12%	1%
PGx evidence is relevant to medication decisions for most of my patients.	3%	13%	49%	29%	4%
PGx is unlikely to reach the level of necessary evidence to individualize therapy.	5%	35%	49%	9%	1%

	Yes	No	Not Sure
Are you likely to recommend the incorporation of PGx into clinical practice to other healthcare providers?	52%	4%	44%
In your opinion, should there be more widespread clinical use of PGx in your area of medical practice?	63%	1%	36%
Do you think that genetic results may influence drug therapy?	92%	1%	7%

PGx = pharmacogenomics

Most notably, providers believed pharmacogenomics is relevant and useful, with more experienced providers being least skeptical about its usefulness. Almost all providers (92%) said that genetic results may influence drug therapy. Although half (49%) of providers are not sure whether pharmacogenomics is likely to reach the level of necessary evidence to individualize prescribing, few (22%) were skeptical about its potential usefulness. Interestingly, with increasing years in experience, providers became less skeptical about the usefulness of pharmacogenomics – 23% of trainees were skeptical, compared to 19% of those with 1–10 years of experience and only 3% of those with 11 or more years of experience.

Despite half (49%) of providers being unsure about whether pharmacogenomic evidence is relevant to medication decisions for most of their patients, providers were optimistic about the clinical utility of pharmacogenomics in their specialty. In fact, 63% said there should be more widespread use of pharmacogenomics in their area of medical practice. About half (52%) were likely to recommend incorporation of pharmacogenomics into clinical practice to other healthcare providers. Most of the remainder (44%) were unsure. Providers were split on the question of how pharmacogenomic information would affect medication decisions: 27% thought pharmacogenomic results may make medication decisions easier, 34% said more complicated, and 39% were unsure, with CRNA/APNs being the most hopeful about pharmacogenomic information making medication decisions easier (48% compared to 20–29% in other groups, p<0.05, comparing CRNA/APN to MD-F and MD-H).

Experiences with pharmacogenomics

Almost all surveyed providers had never ordered a pharmacogenomic test nor discussed a genetic result of any kind with a patient in the past 6 months (98% and 89%, respectively). A similar percentage (94%) reported that pharmacogenomic test results have “almost never” or “never” changed how they have prescribed or administered medications within the last 6 months. Less than half (42%) have discussed pharmacogenomics with other healthcare providers. Those in training especially were less likely to have discussed pharmacogenomics with other healthcare providers (30%, compared to 52% to all other providers post-training).

Interestingly, providers, especially trainees, reported not routinely receiving information about pharmacogenomics. When information was communicated, providers cited journal articles (26%), materials provided from this study (i.e. The ImPreSS Trial, 19%), medical conferences (8%), drug labels (4%), and advertisements (1%) as sources of information about pharmacogenomics. Many (42%) said they almost never receive information about pharmacogenomics, with more trainees saying they almost never receive information about pharmacogenomics (59% compared to 29% of providers with 1–10 years and 30% of providers with 11 or more years of experience).

Pharmacogenomic tests

Responses to questions regarding pharmacogenomic testing are outlined in Table 4. The majority of providers (89%) were not sure when a pharmacogenomics test is available. Most were unsure whether ordering a pharmacogenomic test is too difficult and whether obtaining a pharmacogenomic test takes too long (65% and 65%). Only 9% of respondents answered somewhat or strongly agreed to ‘patient pharmacogenomic testing is not worth the financial costs’; however, 72% were unsure.

Table 4:

Questions regarding pharmacogenomic testing.

	Disagree Strongly	Disagree Somewhat	Not Sure	Agree Somewhat	Agree Strongly
I am usually sure about whether there is an available test to perform PGx testing.	38%	35%	15%	9%	2%
Even when I know a PGx test is available, it is difficult to order.	0%	3%	65%	24%	9%
Obtaining PGx testing takes too long.	0%	3%	65%	26%	7%
Patient PGx testing is not worth the financial costs.	2%	20%	69%	7%	3%

PGx = pharmacogenomics

Barriers to clinical implementation of pharmacogenomics

Providers were asked to indicate what they think is the greatest current barrier to more widespread clinical adoption of pharmacogenomics in their practice (i.e., asked to select one from a list of options, as shown in Appendix A). The top cited barriers included ‘testing is not worth the financial costs’ (17% of all providers stated this was the leading barrier), followed by ‘my awareness about the existence of pharmacogenomics information is lacking’ (13%), and ‘there is insufficient pharmacogenomics information for most drugs’ (13%).

DISCUSSION

This study explored the attitudes and perspectives of a diverse group of anesthesia, critical care, and pain medicine providers (including physicians, nurses, mid-level providers, and pharmacists) at a tertiary academic medical center on the emerging topic of pharmacogenomics, specifically with respect to its perceived and potential future clinical application. Importantly, almost none of our surveyed providers had previously utilized pharmacogenomic tests in clinical practice. Despite this, most saw pharmacogenomics as increasingly important for future practice, and physicians with more years of experience felt the most informed about pharmacogenomics and were most ready to consider its use. Key barriers to future use were a self-perceived lack of understanding of the field, a desire for clear guidelines on use of results, and questions about financial costs/test coverage. Identifying these key areas and sampling current perceptions on pharmacogenomics are thus highly valuable in planning and anticipating the next stages of genomic adoption in perioperative care. While it is acknowledged that the treating providers at an academic medical center may not be entirely representative of general clinicians regarding genomic adoption, our overall learnings are likely to be informative because academic and affiliated early-adopters are exactly the types likely to lead genomic advances into wider practice.

Most of our surveyed anesthesia, critical care and pain medicine providers appeared not to have access to regular educational materials about pharmacogenomics, especially early-career clinicians. These findings are comparable to a study conducted by Rahawi et al.[35] in pediatricians in the U.S. and Japan, which similarly found that less than 10% of all respondents reported being very familiar with pharmacogenetics. However, that study conversely found that a slightly higher rate of pediatricians who had been practicing for 0–4 years felt they were familiar with pharmacogenetics, compared to those with more years of experience (12% compared to ~8%, respectively). Another study among military family medicine physicians by Deluca et al.[36] revealed that 43% of providers had not received any education on pharmacogenomics (including self-education). Over half of respondents from the Deluca et al. study thought it is important to receive training on the use of genetic information to inform appropriate prescription drug use (45% of respondents were undecided). Similarly, and even more strongly, the large majority of all providers in our study (84%) thought that the study of pharmacogenomics should be included in formal medical training.

Importantly, our current survey research was conducted prior to providers receiving any patient-specific pharmacogeonomic results. This highlights an opportunity to educate and engage providers about pharmacogenomics, especially in the context of clinical research efforts. It may very well be that providers “learn” pharmacogenomics by actually receiving and considering pharmacogenomic results during clinical care, especially in the context of early clinical implementation studies. We will follow changes in providers’ responses longitudinally over the course of the ImPreSS trial to assess changes in understanding, perceptions, opinions, and experiences over time.

It is acknowledged that the majority of respondents in our study were physicians. At many institutions, pharmacists play key roles in the consideration and adoption of pharmacogenomic implementation programs.[37–40] From a clinical workflow standpoint, in our ImPreSS Trial anesthesia physicians will make all medication decisions prior to and during surgery, as well as during the recovery period (in the Post-Anesthesia Care Unit, PACU) and as attending physicians in charge of care in select surgical intensive care units (ICUs). However, pharmacists will have a key role in guiding prescription decisions for patients who require such post-operative critical care (by rounding with the physician teams in the ICU), as well as for patients requiring dedicated pain management consultations (pharmacists are integrally involved in direct care as part of the Acute Pain Consultation Service). We will therefore longitudinally follow changes in pharmacists’ perceptions and experiences with pharmacogenomic-guided therapy within these clinical workflows.

Our study had several limitations. First, this study was conducted at a single academic tertiary care hospital. While it is possible that our institutional learning climate views genomics more favorably than some others, this seems unlikely to have greatly impacted the results since there was no pre-existing program or mechanism for testing or utilization of pharmacogenomic results within our medical center’s anesthesia and post-operative care settings, and almost none of the surveyed clinicians had ever utilized a pharmacogenomic test at the time of the survey. We also included a diverse group of clinicians (including nurses, mid-level providers, pharmacists, and housestaff) who were similarly inexperienced with actual use of pharmacogenomics, increasing generalizability. The future advancement of pharmacogenomics is likely to be led by academic tertiary care providers, and our findings regarding “time since training” which correlated with self-perceived “awareness about pharmacogenomics” strongly signals an educational—rather than peer behavioral/institutional influence—on attitudes towards potential genomic adoption. Notably, only 2 of the 149 responding providers were formally grant-funded investigators in ImPreSS with roles to support the subsequent implementation study. Participating providers were given no incentive to participate. Additionally, while this is a baseline survey study in which no intervention had yet occurred, additional learnings about clinical relevance and potential utility will be incrementally included and important, and will be achieved through future survey and behavioral assessments after pharmacogenomic results are delivered in the randomized phase of the ImPreSS trial. Finally, as with any survey instrument, there is a potential for differences in comprehension and interpretation of questions amongst participants, although we mitigated this possibility by extensive pre-testing of the survey instrument among different provider types including physicians, pharmacists, and trainees. Given that the questions had a set number of responses, it is also possible that some questions could have been more informative with the use of in-person interviews or open-ended focus group discussions.

In summary, our study found that anesthesia, critical care, and pain medicine providers are optimistic about considering pharmacogenomics and its potential for future perioperative care. Addressing providers’ desire for additional education about the topic will be important, in addition to eventually solving practical obstacles such as awareness about available tests (when clinically indicated) and desires for clear guidelines about how to use pharmacogenomic information during prescribing/administration decisions. These pre-implementation considerations are important for genomic adoption in general, and highlight perhaps more similarities than differences between provider attitudes about adoption of pharmacogenomics in the perioperative setting and other medical settings. These themes offer a path to informing the next wave of genomic applications in anesthesia and critical care.