About

Alisa J. Stephens Shields, Ph.D., is an Associate Professor of Biostatistics in the Department of Biostatistics and Epidemiology at the Hospital of the University of Pennsylvania and a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics within the Perelman School of Medicine at the University of Pennsylvania. She is also a member of the Graduate Group in Epidemiology and Biostatistics and serves as the Director of the Biostatistics and Data Science Core at the Penn Center for AIDS Research (CFAR). Her educational background includes a B.S. in Mathematics with a minor in Spanish from the University of Maryland, an A.M. in Biostatistics from Harvard University, and a Ph.D. in Biostatistics from Harvard University. Her research interests encompass clinical trials, particularly cluster-randomized trials, longitudinal data analysis, and causal inference with an emphasis on semiparametric methods. She collaborates on projects such as the Testosterone Trials, the Multidisciplinary Approach to Pelvic Pain Network, and various initiatives focused on the prevention and treatment of HIV. Dr. Shields has contributed to the field through her work on statistical methods for treatment effect estimation, and her research has been published in various scientific journals.

Research topics

• Medicine
• Internal medicine
• Physical therapy
• Surgery
• Family medicine
• Virology
• Physical medicine and rehabilitation
• Psychiatry
• Anesthesia

Selected publications

• Cost Analysis of a Scalable Clinician Communication Intervention to Increase HPV Vaccine Initiation

  PEDIATRICS · 2025-02-05 · 1 citations

  article

  BACKGROUND AND OBJECTIVE: For a previous longitudinal cluster randomized controlled trial (2018-2019), we randomized 48 primary care pediatric practices to online communication training vs usual care. Online communication training reduced missed opportunities (MOs) for initial human papillomavirus (HPV) vaccination at well-child care (WCC) visits by 6.8 percentage points among children aged 11-17 years. The current study estimated implementation costs of the communication training intervention at WCC visits. METHODS: We analyzed monthly surveys completed by intervention practice lead clinicians to track clinician plus office staff personnel hours devoted to implementing the intervention. We converted personnel time into 2019 US dollars using national median hourly wages for physicians and other health care workers; we tracked nonpersonnel costs. We calculated costs per practice (overall and by practice size) and estimated costs per averted MO for HPV vaccine initiation using an effectiveness estimate determined by grouped logistic regression at the practice level. RESULTS: Practices varied from 1 to 24 clinicians (mean = 7.5) and from 241 to 8866 visits (mean = 2353) during the 6-month intervention. Total intervention costs varied substantially across the 24 intervention practices from $370 to $6653, with a mean of $2003 (95% CI, $1377-$2762) and median of $1305. The incremental cost per averted MO for HPV vaccine initiation at WCC visits averaged $110 ($212 in practices with 1 or 2 physicians and $94 in practices with 3 or more physicians). CONCLUSIONS: The implementation cost per averted MO for HPV vaccine initiation at WCC visits of this online communication training intervention was modest, particularly among larger pediatric practices.

  PublisherDOI

• Provision of COVID-19 Self-Test Kits to Patients for Distribution to Social Contacts

  JAMA Network Open · 2025-06-04

  articleOpen access

  Importance: Widespread and equitable access to testing remains critical to controlling the COVID-19 pandemic, which has disproportionately affected medically underserved communities. Objective: To determine whether secondary distribution of COVID-19 self-test (ST) kits, in which an individual distributes ST kits to contacts in their social networks, increases COVID-19 testing. Design, Setting, and Participants: The COVID-19 Self-Testing Through Rapid Network Distribution study was a randomized clinical trial conducted between May 2021 and September 2023 at 4 federally qualified health centers serving medically underserved populations in Philadelphia, Pennsylvania. Participants were adults aged 18 years or older presenting to federally qualified health centers without SARS-CoV-2 infection in the past 90 days. Participants were randomized 1:1 to receive 5 COVID-19 ST kits or 5 clinic test referral cards to distribute to contacts in their social network, and testing among their social network contacts was measured. Investigators were masked to study group assignment. Data were analyzed from December 11, 2023, to August 23, 2024. Intervention: Participants in the intervention group received 5 COVID-19 ST kits; control participants received 5 clinic test referral cards. Main Outcomes and Measures: The primary outcome was confirmed testing among at least 2 network contacts 8 weeks after randomization. Secondary outcomes included the proportion of participants with at least 1 network contact tested and total number of network contacts reached. Results: A total of 776 participants (median [IQR] age, 44 [32-57] years; 428 [55.2%] cisgender female) were included in the study, of whom 388 participants were randomized to the ST intervention group and 388 participants were randomized to the control group. There were 112 Hispanic or Latine participants (14.4%), 459 non-Hispanic Black participants (59.1%), and 120 non-Hispanic White participants (15.5%). There was no difference between study groups in the primary outcome, with 5 participants (1.3%) in the ST group vs 2 participants (0.5%) in the control group having at least 2 contacts confirmed tested at the 8-week follow-up (risk difference, 0.0077; 95% CI -0.0056 to 0.0210; P = .45). Conclusions and Relevance: This randomized clinical trial found that secondary distribution of COVID-19 ST kits had no effect on confirmed testing rates among network contacts, which were low in both study groups. Despite these null findings, the study provides insight that may be useful when designing and implementing ST trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04797858.

  PublisherOA PDFDOI

• Towards precision medicine in clinical trials for the treatment of urologic chronic pelvic pain syndrome: lessons from the MAPP Research Network

  Nature Reviews Urology · 2025-04-30 · 6 citations

  review1st authorCorresponding
  PublisherDOI

• A series of randomized trials of behavioral economic interventions to increase racial and ethnic diversity of research participants: Rationale and design of ITERATE

  American Heart Journal · 2025-03-31 · 2 citations

  articleOpen access

  RATIONALE: Prospective clinical research studies are essential for determining the effectiveness and safety of drugs, medical devices, and healthcare delivery interventions. However, low enrollment, particularly among Black and Hispanic patients, challenges the generalizability of results and fairness of research. Leveraging insights from behavioral economics to modify the content of messages recruiting patients to join research studies may increase enrollment and representativeness of trial populations. PRIMARY HYPOTHESIS: Method of outreach, source of outreach, message framing, and financial incentives will have important effects on enrollment fraction of Black and Hispanic patients electronically approached for participation in a prospective clinical research study. DESIGN: ITERATE (NCT05827718) is a series of 4 randomized clinical trials (RCTs) designed to rigorously, systematically, and iteratively test the effects of different messaging strategies informed by behavioral economic theory on the enrollment of Black and Hispanic individuals into the Penn Medicine BioBank (PMBB), a prospective registry. For all 4 RCTs, we will identify patients eligible for enrollment in the PMBB (those with ≥ 1 encounter with the University of Pennsylvania Health System in the past 3 months, a phone number able to receive text messages or a valid email address on file, no history of consenting to or declining enrollment in the PMBB, and able to provide their own consent) and randomly assign them to receive different outreach messages. RCT 1 will test the method of outreach (email vs. text message vs. email + text message); RCT 2, source of outreach (research team vs. clinical team); RCT 3, message framing (appeal to altruism vs. appeal to social proof vs. control); and RCT 4, financial incentive (none vs. medium guarantee vs. small guarantee + small lottery vs. medium lottery vs. large lottery). In each RCT, at least 50% of the participants will be Black or Hispanic. The primary outcome of each RCT is enrollment fraction, defined as the number of participants who enroll in the PMBB divided by the total number of participants who received an outreach message, compared between arms among both Black and Hispanic patients. Secondary outcomes will include overall enrollment fraction and enrollment fraction among White patients. The "winning" strategies in earlier RCTs will be incorporated as the "standard of care" in the subsequent RCTs.

  PublisherDOI

• The impact of opioid withdrawal symptoms on pain outcomes in enriched enrollment randomized withdrawal trials: a mediation meta-analysis of trials submitted to the US Food and Drug Administration

  Pain · 2025-12-24

  article

  ABSTRACT: The validity of enriched enrollment randomized withdrawal (EERW) trials to evaluate the efficacy of opioids for the treatment of chronic pain has been questioned. Enriched enrollment randomized withdrawal trials include an open-label titration phase to identify treatment responders who tolerate the drug, followed by a double-blind randomized phase in which responders either continue the drug or switch to placebo. A key concern is that the apparent efficacy of opioids in EERW trials may be attributable to induction of withdrawal symptoms among participants switched to placebo. We used individual participant data from 13 EERW trials (N = 5070) submitted to the US Food and Drug Administration (FDA) to estimate the extent to which withdrawal symptoms mediated the treatment effect of opioids on pain. The primary mediator was the maximum Subjective Opioid Withdrawal Scale score during the randomized phase. The primary outcome was the change in pain intensity (numeric rating scale) from randomization baseline to week 12. The pooled average treatment effect was -0.71 (95% confidence interval [CI], -0.87 to -0.55) on the numeric rating scale. Withdrawal symptoms did not significantly mediate the effect of opioids on pain overall, accounting for 2% of the pooled treatment effect (95% CI, -1% to 4%). However, significant mediation was observed in 3 individual trials (range, 8% to 28% of treatment effect mediated). Although withdrawal symptoms did not systematically bias efficacy findings in EERW trials of opioids submitted to the FDA, they contributed to overestimation in some cases. These findings support incorporating mediation analyses in future EERW trials to ensure accurate interpretation of study results.

  PublisherDOI

• A Bundled, Practice-Based Intervention to Increase HPV Vaccination

  PEDIATRICS · 2025-01-06 · 6 citations

  articleOpen accessSenior author

  BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) vaccination rates are suboptimal, and missed vaccination opportunities are common. We hypothesized that a bundled intervention improves missed HPV vaccination opportunities. METHODS: We used a pre-post design to assess differences in HPV vaccine missed opportunities (visits when vaccine-eligible adolescents are not vaccinated). We compared rates for a 12-month period before vs those for a 6-month period (February 23, 2022, to August 9, 2022) during a bundled intervention. We implemented the bundled intervention in 24 primary care pediatric practices that had been usual care controls for a prior randomized trial. The bundled intervention involved 3 components: online clinician training on HPV vaccine communication, performance feedback on missed HPV vaccination opportunities, and clinician prompts for HPV vaccination. As a secondary analysis, we compared missed opportunities for these 24 practices vs 48 contemporaneous comparison group practices identified retrospectively. RESULTS: For well-child care (WCC) visits, missed HPV vaccination opportunities were improved during vs before the intervention by 4.8 percentage points (95% CI, -7.2% to -2.4%) for initial HPV vaccine doses and a modest 2.2 percentage points (95% CI, -4.4% to -0.0%) for subsequent doses. For other visit types, findings ruled out changes beyond minimal improvements. Missed vaccination opportunity rates for initial HPV vaccination at WCC visits were similar for the 24 intervention practices vs the 48 comparison practices for a 4.5-year period before the intervention, but they improved for intervention practices and worsened for comparison practices during the intervention period (difference, -6.6%; 95% CI, -9.3% to -3.8%). CONCLUSIONS: This bundled intervention appeared to improve HPV vaccination during WCC visits.

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• Behavioral Economic Strategies to Promote Cardiovascular Clinical Trial Enrollment Among Underrepresented Populations: A Discrete Choice Experiment

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  articleSenior author

  Abstract Rationale: Black, Hispanic/Latinx, female, and rural US populations face disparities in cardiovascular disease risk factors, care, outcomes, and interventions, in part from underrepresentation in clinical trials. Behavioral economics (BE), principles of economics and psychology to understand decision-making, may improve trial enrollment and retention, but has not been evaluated among underrepresented populations. Therefore, we aimed to quantify preferences for BE strategies to optimize enrollment representation. Methods: We conducted a discrete choice experiment (DCE), a quantitative method used to elicit preferences without directly asking, to determine BE strategies’ influence on trial enrollment among adult participants who identified as Black, Hispanic/Latinx, female, and/or living in rural areas. Each participant completed 12 forced-choice tasks in random order. For each task, participants were presented with two hypothetical cardiovascular trials and selected which trial they would be more likely to enroll in. Study conditions were identical except for: enrollment method (opt-in, opt-out), recruiter role (physician they followed with longitudinally, physician researcher, research staff), and incentive (none, $150 cash, $150 gift card, $150 debit card). We performed logistic mixed effects models to determine associations of BE strategies with enrollment consent, using crossed random effects for participant and task number, overall and by subgroup. Results: We surveyed 247 eligible participants 1/3/24-6/18/24 (2,964 surveys). 147 (60%) identified as Black, 37 (15%) Hispanic/Latinx, 177 (72%) female, and 88 (36%) living in rural areas. Median age was 35 (IQR 28-50). Participants overall revealed preferences for participating in studies when an opt-in recruitment strategy was employed vs opt-out (OR=0.55, 95% CI=0.49-0.62 vs OR=0.45, 95% CI=0.38-0.52, p<0.001); the recruiter was a physician they followed with longitudinally vs a physician researcher or research staff (OR=0.63, 95% CI=0.56-0.69 vs OR=0.48, 95% CI=0.41-0.55, p<0.001; OR=0.41, 95% CI=0.33-0.48, p<0.001); and the incentive was $150 cash vs none, $150 gift card, and $150 debit card (OR=0.75, 95% CI=0.68-0.82 vs OR=0.09, 95% CI=0.06-0.13, p<0.001; OR=0.54, 95% CI=0.45-0.63, p<0.001; OR=0.71, 95% CI=0.64-0.79, p=0.09). Effect estimates were similar across subgroups (Table). Conclusions: Leveraging DCE methodology, Black, Hispanic/Latinx, female, and/or rural areas participants revealed preferences for participating in studies that utilized opt-in recruitment performed by a physician they saw longitudinally, with $150 cash incentive, with similar findings across subgroups. Future work is needed to confirm our findings, and test our findings in larger sample sizes of underrepresented US populations and in the context of actual prospective studies, to ultimately improve enrollment representativeness.

  PublisherDOI

• Comparative Effectiveness of Perioperative Antibiotic Regimens to Prevent Surgical Site Infections in Pediatric Liver Transplant Recipients

  Clinical Infectious Diseases · 2024-02-21 · 4 citations

  article

  BACKGROUND: Surgical site infections (SSIs) are a common complication in liver transplant (LT) recipients. Lack of pediatric prophylaxis guidelines results in variation in preventative antibiotic regimens. METHODS: We performed a retrospective observational study of LT recipients <18 years old using a merged data set that included data from the Pediatric Health Information System and the United Network for Organ Sharing between 2006 and 2017. The exposure was defined as the antibiotic(s) received within 24 hours of LT, with 6 categories, ranging from narrow (category 1: cefazolin), to broad). The primary outcome was presence or absence of SSI in the index admission. Mixed-effects logistic regression compared the effectiveness of each category in preventing SSI, relative to category 1. RESULTS: Of the 2586 LT, 284 (11%) met SSI criteria. The SSI rate was higher in the younger subcohort (16.2%) than in the older (8.6%), necessitating a stratified analysis. Antibiotics from category 5 were most commonly used. In the younger subcohort, the adjusted risk was increased in all categories compared with the reference, most notably in category 3 (odds ratio [OR], 2.58 [95% confidence interval: .69-9.59]) and category 6 (2.76 [.66-11.56]). In the older subcohort, estimated ORs were also increased for each category, most notably in category 4 (2.49 [95% confidence interval: .99-6.27]). None of the ORs suggested benefit from broader-spectrum prophylaxis. Our E-value assessment suggests that it's unlikely there is unmeasured confounding by indication to the degree necessary to revert ORs to protective. CONCLUSIONS: There was wide variation in antibiotic prophylaxis. Adjusted analyses did not reveal a protective benefit of broader-spectrum prophylaxis in either subcohort, suggesting that narrower regimens may be adequate.

  PublisherDOI

• Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium

  Annals of the Rheumatic Diseases · 2024-11-14 · 6 citations

  articleOpen access

  OBJECTIVES: To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting. METHODS: In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi). RESULTS: Among 627 patients with PsA, three clusters were identified: mild PsA and psoriasis only (PsO) (Cluster 1, 47.4%), severe PsA and mild PsO (Cluster 2, 34.3%) and severe PsA and severe PsO (Cluster 3, 18.3%). Among 339 patients starting or changing, significant differences in response were observed (mean follow-up of 0.7 years, SD 0.8), with Cluster 3 showing the largest improvements in cDAPSA and PsAID. No differences were found among those starting TNFi (n=218). cDAPSA remission and PsAID patient acceptable symptom state were achieved in 10% and 54%, respectively. Clusters remained stable over time despite treatment changes, though some transitions occurred, notably from Cluster 3 to milder clusters. CONCLUSION: Data-driven clusters with distinct therapy responses identified in this real-world study highlight the extensive heterogeneity in PsA and the central role of psoriasis and musculoskeletal severity in treatment outcomes. Concurrently, these findings underscore the need for better outcome measures, particularly for individuals with lower disease activity.

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• Modulation of circulating free testosterone fraction by testosterone, dihydrotestosterone, and estradiol during testosterone replacement therapy

  Andrology · 2024-08-02 · 6 citations

  article

  BACKGROUND: Testosterone, estradiol, and dihydrotestosterone share common ligand binding sites on sex hormone binding globulin and albumin. It is unknown whether and how changes in testosterone, dihydrotestosterone, and estradiol concentrations during testosterone replacement therapy affect free testosterone fraction. OBJECTIVE: To determine the effect of changes in testosterone, dihydrotestosterone, and estradiol concentrations on free testosterone fraction during testosterone replacement therapy of men with hypogonadism. METHODS: Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and dihydrotestosterone concentrations over 12 months of testosterone replacement therapy with changes in free testosterone fraction, measured using equilibrium dialysis. We used random forests to evaluate the associations of predicted mean changes in free testosterone fraction with changes in circulating concentrations of each hormone at low, mean, or high change in the other two hormones. RESULTS: Testosterone replacement therapy not only increased total testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations, but also the percent free testosterone, even though sex hormone binding globulin levels did not change. The predicted changes in free testosterone fraction during testosterone replacement therapy exhibited a non-linear relationship with changes in each of total testosterone, dihydrotestosterone, and estradiol concentrations. Greater increases in testosterone, dihydrotestosterone, and estradiol levels during testosterone replacement therapy were each associated with higher model-predicted percent free testosterone. Substantially smaller changes in molar concentrations of estradiol and dihydrotestosterone had a greater effect on percent free testosterone than those in testosterone. CONCLUSION: During testosterone replacement therapy of men with hypogonadism, changes in testosterone, dihydrotestosterone, and estradiol concentrations each altered percent free testosterone non-linearly. Small changes in estradiol concentrations exerted much larger effect on the free testosterone fraction than testosterone and dihydrotestosterone, suggesting complex interactions of the three hormones with the binding proteins. Assessment of changes in free testosterone during testosterone replacement therapy should include consideration of changes in all three hormones.

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Recent grants

• Molecular & Translational Immunotechnology Core

  NIH · $36.7M · 1999–2029

Frequent coauthors

• J. Richard Landis

  Children's Hospital of Philadelphia

  41 shared

• Bruce D. Naliboff

  University of California, Los Angeles

  40 shared

• Ronald S. Swerdloff

  Harbor–UCLA Medical Center

  40 shared

• H. Henry Lai

  Washington University in St. Louis

  40 shared

• J. Quentin Clemens

  Michigan Medicine

  39 shared

• Xiaoling Hou

  39 shared

• Chris Mullins

  National Institutes of Health

  38 shared

• Alvin M. Matsumoto

  37 shared

Education

• B.S., Mathematics with Spanish minor

  University of Maryland

  2006

• Other, Biostatistics

  Harvard University

  2009

• Ph.D., Biostatistics

  Harvard University

  2012