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      string(233) "NCT00638690 - A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Docetaxel-Based Chemotherapy"
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  ["project_title"]=>
  string(138) "Baseline Cardiometabolic Burden and the Survival Effect of Abiraterone in Advanced Prostate Cancer: An IPD Analysis of Four Phase 3 Trials"
  ["project_narrative_summary"]=>
  string(802) "Men with advanced prostate cancer often have hypertension, diabetes, cardiovascular disease, or reduced kidney function. These conditions may influence the benefit and tolerability of abiraterone plus prednisone, but published reports cannot show whether treatment effects change as baseline burden accumulates. We will analyze de-identified data from four randomized phase 3 trials. Within each trial, we will compare abiraterone-based therapy with its control across a prespecified 0–4 burden count. We will estimate relative and absolute survival effects and selected clinically important toxicities, synthesize compatible mCRPC trials, and assess LATITUDE separately as cross-stage validation. The aim is to support individualized treatment discussions and monitoring for trial-eligible patients."
  ["project_learn_source"]=>
  string(10) "web_search"
  ["principal_investigator"]=>
  array(7) {
    ["first_name"]=>
    string(9) "Guangwen "
    ["last_name"]=>
    string(3) "Yin"
    ["degree"]=>
    string(3) "PhD"
    ["primary_affiliation"]=>
    string(53) "The First Affiliated Hospital of Zhengzhou University"
    ["email"]=>
    string(15) "gwyin67@126.com"
    ["state_or_province"]=>
    string(5) "Henan"
    ["country"]=>
    string(5) "China"
  }
  ["project_key_personnel"]=>
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    [0]=>
    array(6) {
      ["p_pers_f_name"]=>
      string(8) "Mingxuan"
      ["p_pers_l_name"]=>
      string(2) "Ma"
      ["p_pers_degree"]=>
      string(19) "Master of Medicine "
      ["p_pers_pr_affil"]=>
      string(53) "The First Affiliated Hospital of Zhengzhou University"
      ["p_pers_scop_id"]=>
      string(0) ""
      ["requires_data_access"]=>
      string(3) "yes"
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  }
  ["project_ext_grants"]=>
  array(2) {
    ["value"]=>
    string(3) "yes"
    ["label"]=>
    string(65) "External grants or funds are being used to support this research."
  }
  ["project_funding_source"]=>
  string(69) "Henan Zhongyuan Talents Program (Yucai Series), Henan Province, China"
  ["project_date_type"]=>
  string(18) "full_crs_supp_docs"
  ["property_scientific_abstract"]=>
  string(1493) "Background: Abiraterone plus prednisone improves survival in advanced prostate cancer but can cause mineralocorticoid toxicity. Common cardiometabolic conditions may affect outcomes, but aggregate reports cannot assess their cumulative effect.

Objective: To test whether baseline cardiometabolic burden modifies the randomized effect of abiraterone-based therapy on overall survival (OS) and quantify burden-specific efficacy and selected toxicity differences.

Study Design: Individual participant data analysis of four phase 3 trials, with primary synthesis of compatible mCRPC trials and separate cross-stage validation in LATITUDE.

Participants: About 3,800 randomized participants.

Primary and Secondary Outcome Measure(s): Primary: OS. Secondary: radiographic progression-free survival (rPFS), 24-month survival and restricted mean survival time (RMST), grade ≥3 mineralocorticoid-related toxicity, and adverse-event-related study-drug modification.

Statistical Analysis: The exposure is a prespecified 0–4 count of hypertension, diabetes, established cardiovascular disease, and renal impairment. Trial-specific intention-to-treat Cox models will estimate treatment-by-burden interactions. Compatible mCRPC estimates will undergo two-stage synthesis; LATITUDE will be separate. Absolute effects will be standardized by burden group. Competing-risk methods will analyze toxicity; missing baseline data will be multiply imputed within trials.

"
  ["project_brief_bg"]=>
  string(3193) "Abiraterone acetate inhibits CYP17 and, with prednisone and continued androgen deprivation, improves survival in metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer. The pivotal COU-AA-301, COU-AA-302, LATITUDE, and ABI-PRO-3002 trials span post-docetaxel mCRPC, chemotherapy-naïve mCRPC, and newly diagnosed high-risk metastatic hormone-sensitive disease.[1–7] Their participant-level data permit randomized treatment comparisons across distinct clinical settings.

Men with advanced prostate cancer frequently have hypertension, diabetes, cardiovascular disease, or reduced renal function. Abiraterone can cause hypertension, hypokalemia, and fluid retention through mineralocorticoid excess, while concomitant prednisone can affect glycemic control. Aggregate meta-analysis shows increased cardiovascular toxicity with androgen-receptor signaling inhibitors,[8] and a recent IPD study estimated average serious-adverse-event risks of abiraterone in mCRPC.[9] Neither approach determines whether cumulative baseline cardiometabolic burden modifies the randomized OS effect.

The clinical uncertainty is therefore not whether abiraterone works on average, but whether its relative and absolute survival effects remain consistent as baseline burden accumulates, and what selected toxicity differences accompany treatment within each burden group. Credible treatment-effect-heterogeneity analysis requires a prespecified exposure, formal treatment-by-exposure interaction testing, preservation of randomized comparisons, and presentation of absolute as well as relative effects.[10,11] Because the renal domain may be defined from a single baseline eGFR rather than confirmed chronicity, we use the term “baseline cardiometabolic burden,” not “multimorbidity.”

This project is deliberately distinct from YODA Project 2025-0040, which applies cardiovascular-risk algorithms and examines MACE/MACE2.[12] Our primary endpoint is OS and our exposure is a transparent count of four observed baseline domains; MACE/MACE2 are outside scope. It is also distinct from the published IPD safety analysis,[9] which assessed average adverse-event risk rather than randomized OS effect modification by baseline burden.

Trial structure is central to the design. The mCRPC trials will be analyzed independently and synthesized only when exposure and outcome definitions are compatible. COU-AA-302 is the principal chemotherapy-naïve mCRPC analysis, COU-AA-301 provides independent post-docetaxel replication, and ABI-PRO-3002 provides supportive mCRPC evidence. LATITUDE will be reported separately as cross-stage validation. An overall four-trial synthesis will be supportive and undertaken only if clinical and statistical compatibility is adequate.

The study will generate clinically useful knowledge by quantifying randomized relative and absolute treatment effects in a common vulnerable population. Findings could improve treatment discussions and identify monitoring priorities while recognizing that the source trials excluded some patients with severe or uncontrolled cardiometabolic disease.

"
  ["project_specific_aims"]=>
  string(1425) "Overall objective: To determine whether baseline cardiometabolic burden modifies the randomized survival effect of abiraterone plus prednisone in advanced prostate cancer.

Aim 1 (primary): Within each mCRPC trial, estimate the interaction between randomized treatment and a prespecified 0–4 baseline burden count for OS, then synthesize clinically and statistically compatible mCRPC estimates. The pooled mCRPC treatment-by-count interaction is the sole primary hypothesis test. COU-AA-302 is the principal analysis, COU-AA-301 provides independent replication, and ABI-PRO-3002 provides supportive evidence.

Aim 2: Quantify treatment effects within burden categories (0, 1, and ≥2 domains), including hazard ratios, 24-month survival differences, 24-month RMST differences, and rPFS effects where definitions permit. LATITUDE will be analyzed separately as cross-stage validation. A four-trial overall synthesis will be supportive and performed only if compatibility is adequate.

Aim 3: Determine whether baseline burden modifies selected treatment-emergent toxicity: grade ≥3 mineralocorticoid-related toxicity within 12 months and adverse-event-related interruption, reduction, or permanent discontinuation of the randomized study drug. These are secondary analyses. Survival and toxicity estimates will be presented side by side rather than combined using unmeasured preference weights.

"
  ["project_study_design"]=>
  array(2) {
    ["value"]=>
    string(7) "meta_an"
    ["label"]=>
    string(52) "Meta-analysis (analysis of multiple trials together)"
  }
  ["project_purposes"]=>
  array(4) {
    [0]=>
    array(2) {
      ["value"]=>
      string(56) "new_research_question_to_examine_treatment_effectiveness"
      ["label"]=>
      string(114) "New research question to examine treatment effectiveness on secondary endpoints and/or within subgroup populations"
    }
    [1]=>
    array(2) {
      ["value"]=>
      string(49) "new_research_question_to_examine_treatment_safety"
      ["label"]=>
      string(49) "New research question to examine treatment safety"
    }
    [2]=>
    array(2) {
      ["value"]=>
      string(22) "participant_level_data"
      ["label"]=>
      string(36) "Participant-level data meta-analysis"
    }
    [3]=>
    array(2) {
      ["value"]=>
      string(37) "participant_level_data_only_from_yoda"
      ["label"]=>
      string(51) "Meta-analysis using only data from the YODA Project"
    }
  }
  ["project_research_methods"]=>
  string(1838) "We request de-identified participant-level data, full clinical study reports, protocols/amendments, statistical analysis plans, data definitions, case-report forms, and supporting documentation for four J&J phase 3 trials:

1.	COU-AA-302, NCT00887198 (n=1,088): chemotherapy-naïve, asymptomatic or mildly symptomatic mCRPC; abiraterone acetate plus prednisone versus placebo plus prednisone.

2.	COU-AA-301, NCT00638690 (n=1,195): mCRPC after docetaxel; abiraterone acetate plus prednisone versus placebo plus prednisone.

3.	LATITUDE, NCT01715285 (approximately 1,200 randomized): newly diagnosed, high-risk metastatic hormone-sensitive prostate cancer; abiraterone acetate plus low-dose prednisone plus ADT versus placebo plus ADT.

4.	ABI-PRO-3002, NCT01591122 (n=313): chemotherapy-naïve, asymptomatic or mildly symptomatic mCRPC; abiraterone acetate plus prednisone versus placebo plus prednisone.

The efficacy population will include all randomized participants in each trial's intention-to-treat population with a valid randomization record, analyzed as randomized. Handling of participants without observed post-randomization outcome information will follow prespecified trial rules. No participant will be excluded for adherence, treatment change, or crossover. The safety population will follow each protocol's treated-population definition and include participants who received at least one study-treatment dose.

Sporadically missing baseline predictors will undergo prespecified multiple imputation; outcomes will not be imputed. An entirely uncollected domain will not be coded as absence or imputed. That trial will contribute to descriptive and reduced-domain sensitivity analyses but not the primary four-domain synthesis. No external individual-level data will be used.

"
  ["project_main_outcome_measure"]=>
  string(1949) "Primary outcome: OS, defined within each trial as time from randomization to death from any cause. Participants without recorded death will be censored at the last date known alive according to the protocol/CSR rule.

Secondary efficacy outcomes:

1.	rPFS, defined according to each trial's prespecified radiographic endpoint as time from randomization to radiographic progression or death. Because assessment schedules and definitions may differ, rPFS will be analyzed within trial and synthesized only when clinically compatible.

2.	OS probability at 24 months and RMST through 24 months, an interpretable absolute time-based measure that does not require proportional hazards.[13] Twelve-month estimates will be supportive. A trial will contribute to a horizon only if follow-up and numbers at risk adequately support it.

Secondary safety outcomes:

1.	First treatment-emergent grade ≥3 mineralocorticoid-related toxicity within 12 months: hypertension, hypokalemia, or edema/fluid retention, mapped using protocol CTCAE grades and prespecified MedDRA preferred-term groupings.

2.	First adverse event leading to interruption, reduction, or permanent discontinuation of the randomized study drug within 12 months. Modification will refer to abiraterone/placebo where this can be distinguished from prednisone, ADT, and other background therapy; otherwise the trial-specific definition will be retained and reported.

3.	Individual mineralocorticoid components and serious adverse events will be supportive descriptive outcomes.

For toxicity, time zero is first dose; death before the event is a competing event. Follow-up ends at the earliest of 12 months, last safety assessment, or the applicable protocol-defined risk-period end. For treatment modification, non-adverse-event discontinuation will also be a competing event. Survival and toxicity effects will be reported separately.

"
  ["project_main_predictor_indep"]=>
  string(1761) "The main predictor is baseline cardiometabolic burden: the unweighted count (0–4) of four binary domains present at or before randomization:

1.	Hypertension: documented medical history of hypertension or baseline antihypertensive treatment when the recorded indication supports hypertension.

2.	Diabetes mellitus: documented type 1 or type 2 diabetes or baseline use of glucose-lowering medication.

3.	Established cardiovascular disease: documented coronary artery disease, myocardial infarction, angina, coronary revascularization, heart failure, stroke/transient ischemic attack, or peripheral arterial disease.

4.	Baseline renal impairment: eGFR <60 mL/min/1.73 m², calculated from the closest valid pre-randomization creatinine using the 2021 race-free CKD-EPI creatinine equation,[14] or documented chronic kidney disease when available. A single low eGFR will be interpreted as baseline renal impairment, not proof of chronic kidney disease.

The primary exposure is the count as a linear ordinal term, giving a one-degree-of-freedom treatment-by-burden interaction. Categories of 0, 1, and ≥2 domains will be used for description and standardized absolute effects because counts of 3–4 are expected to be sparse. Individual domains and an alternative eGFR <45 threshold will be sensitivity analyses.

Medical-history terms, medications, diagnoses, and laboratory units will be harmonized through a prespecified crosswalk based on protocols, case-report forms, data dictionaries, and clinical study reports before treatment-outcome modeling. Ambiguous medications without a supporting diagnosis or indication will not establish a domain. Structural non-collection will not be coded as “no.”

"
  ["project_other_variables_interest"]=>
  string(1453) "Trial identifier and randomized treatment are required to preserve within-trial randomized contrasts. Prespecified baseline variables used for description and precision adjustment will include age, geographic region/race where available, ECOG performance status, disease state, prior docetaxel, pain/symptom status, time from initial diagnosis, Gleason score, visceral metastases, bone metastases, number/location of metastatic sites, PSA, alkaline phosphatase, lactate dehydrogenase, hemoglobin, albumin, body mass index, potassium, liver tests, creatinine/eGFR, and protocol randomization strata.

Variables used to define follow-up and outcomes will include randomization and first-dose dates, radiographic assessment and progression dates, last-known-alive and death dates, adverse-event preferred terms/system-organ classes, onset and resolution dates, CTCAE grade, seriousness, relationship, action taken, study-drug exposure, interruption/reduction/discontinuation dates and reasons, and last safety assessment.

Concomitant medications will be used to ascertain baseline domains or describe relevant management, including antihypertensives, glucose-lowering agents, diuretics, antiplatelets/anticoagulants, lipid-lowering treatment, and corticosteroids. Post-randomization variables will not adjust the primary randomized treatment effect. Trial-specific definitions will be retained when valid harmonization is not possible.

"
  ["project_stat_analysis_plan"]=>
  string(4537) "Principles and estimand: The estimand is the intention-to-treat effect of assignment to abiraterone plus prednisone versus randomized control on OS, and its change per additional burden domain. Randomization will be preserved within trial. Consistent with heterogeneity guidance,[10,11] the exposure, interaction, covariates, categories, and sensitivity analyses will be prespecified before outcome modeling. No stepwise selection, outcome-derived cut points, machine-learning subgroup search, or outcome-based count optimization will be used.

Data preparation: Counts, assignments, dates, endpoints, strata, laboratory units, history/medication coding, MedDRA terms, CTCAE grades, and censoring rules will be reconciled against each protocol, SAP, and CSR. Availability and harmonization tables will be completed. Baseline characteristics and missingness will be summarized without balance significance tests.

Trial hierarchy and primary analysis: Each trial will first be analyzed independently. Within each mCRPC trial, a Cox model will include treatment, the 0–4 count, and their interaction, using trial-specific hazards and original strata where feasible. Precision adjustment will prespecify age, ECOG status, visceral metastasis/bone-disease extent, PSA, hemoglobin, alkaline phosphatase, and albumin; nonlinear covariates will use restricted cubic splines with fixed knots. An unadjusted model will be a sensitivity analysis.

The sole primary test is the pooled treatment-by-count interaction across mCRPC trials with all four domains, compatible OS, and adequate follow-up. Trial-specific interaction log-hazard ratios will be combined by two-stage random-effects IPD analysis.[15] Restricted maximum likelihood will estimate heterogeneity; Hartung-Knapp CIs will be used when at least three trials qualify. All trial estimates will be shown. If only two qualify, common-effect and REML estimates will accompany both trial estimates, without claiming precise heterogeneity estimation.

COU-AA-302 is the principal chemotherapy-naïve mCRPC analysis, COU-AA-301 provides post-docetaxel replication, and ABI-PRO-3002 is supportive. LATITUDE will use the same interaction model as separate cross-stage validation. A one-stage trial-stratified Cox model with trial-specific treatment effects and a common interaction will be a sensitivity analysis. Four-trial synthesis will be supportive and require adequate compatibility.

Absolute efficacy: Within burden categories 0, 1, and ≥2, standardized curves will estimate 24-month OS, risk differences, numbers needed to treat when appropriate, and RMST differences with 95% CIs.[13] rPFS will use analogous analyses only with compatible definitions. Schoenfeld residuals and treatment-by-time terms will assess proportional hazards; RMST and time-specific effects will be emphasized if violated.

Safety: Protocol-defined treated populations will be used. Twelve-month cumulative incidence will account for death; non-AE discontinuation will also compete for treatment modification. Cause-specific Cox and Fine-Gray models[16] will include treatment, burden, and interaction. Standardized 12-month risk differences will be reported. Safety interactions are secondary.

Missing data: Outcomes, treatment, and structurally uncollected domains will not be imputed. Sporadically missing baseline data will undergo within-trial chained-equation imputation (50 datasets), including treatment, baseline variables, event indicator, and cumulative hazard.[17] Rubin's rules will combine estimates before synthesis. Complete cases and best/worst plausible domain classification will assess robustness.

Sensitivity analyses will examine individual domains; categorical burden; eGFR <45; adjustment; complete cases; chemotherapy-naïve mCRPC; leave-one-trial-out analyses; and exclusion of ABI-PRO-3002. Disease state-by-treatment-by-burden interaction and four-trial synthesis will be exploratory. Incompatible endpoints or structurally missing domains will not be forced into pooling.

Multiplicity: Two-sided alpha=0.05 applies only to the pooled mCRPC OS interaction. Other estimates will carry 95% CIs and be interpreted as validation, supportive, or exploratory evidence without claims based solely on nominal P values. Effect modification will require coherent magnitude, direction, absolute effects, and cross-trial support. Conclusions will apply to trial-eligible patients within observed cardiometabolic support.

"
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  ["project_timeline"]=>
  string(1354) "Month 0: Execute the Data Use Agreement and obtain secure-platform access.

Months 0–2: Review protocols, amendments, SAPs, case-report forms, data specifications, and CSRs; reconcile datasets; produce the trial-by-variable availability table, harmonization dictionary, endpoint crosswalk, and final locked analysis plan.

Months 2–4: Construct baseline burden domains; validate treatment, outcome, follow-up, and adverse-event variables; complete descriptive and missing-data analyses.

Months 4–6: Conduct trial-specific mCRPC OS models, primary synthesis, diagnostics, imputation, and sensitivity analyses.

Months 6–8: Complete LATITUDE cross-stage validation; estimate standardized OS/RMST and rPFS effects; perform secondary toxicity and competing-risk analyses.

Months 8–9: Interpret results with the clinical/statistical team; prepare tables, figures, and a PRISMA-IPD flow diagram.

Months 9–10: Draft the manuscript and abstract; complete reporting checklists and independent code/result verification.

Months 10–11: Submit the manuscript to a peer-reviewed journal and, if appropriate, an oncology meeting.

Month 12: Provide YODA with the required final report, citation/status updates, and compliant aggregate outputs; close or renew access according to YODA procedures.

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  ["project_dissemination_plan"]=>
  string(1472) "The primary output will be one peer-reviewed Original Article reporting the prespecified mCRPC OS effect-modification analysis, trial-specific estimates, LATITUDE cross-stage validation, absolute efficacy, and selected secondary toxicity results. Candidate journals include European Urology Oncology, Prostate Cancer and Prostatic Diseases, and Frontiers in Oncology or Frontiers in Endocrinology; selection will reflect the completed study's scope and quality. Findings may also be submitted to ASCO Genitourinary Cancers Symposium, ESMO, or a national oncology/urology meeting.

Results will be reported regardless of direction or statistical significance and in accordance with PRISMA-IPD.[18] A plain-language summary will distinguish prognostic burden from treatment-effect modification and avoid recommending treatment withdrawal for groups not directly supported by the data.

The manuscript, conference abstract, and bibliographic information will be reported to YODA within required timelines. Only disclosure-screened aggregate results will leave the secure environment. No participant-level data will be downloaded, shared, or reidentified. Reproducible R code and a data-independent variable/endpoint dictionary may be shared publicly if permitted by the Data Use Agreement; otherwise code will be supplied to YODA. Funders and data providers will be acknowledged transparently and will not control analysis, interpretation, or publication.

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  ["project_bibliography"]=>
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de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005. doi:10.1056/NEJMoa1014618.
Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983-992. doi:10.1016/S1470-2045(12)70379-0.
Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138-148. doi:10.1056/NEJMoa1209096.
Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152-160. doi:10.1016/S1470-2045(14)71205-7.
Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352-360. doi:10.1056/NEJMoa1704174.
Fizazi K, Tran N, Fein L, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20(5):686-700. doi:10.1016/S1470-2045(19)30082-8.
Ye D, Huang Y, Zhou F, et al. A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia. Asian J Urol. 2017;4(2):75-85. doi:10.1016/j.ajur.2017.01.002.
El-Taji O, Taktak S, Jones C, et al. Cardiovascular events and androgen receptor signaling inhibitors in advanced prostate cancer: a systematic review and meta-analysis. JAMA Oncol. 2024;10(7):874-884. doi:10.1001/jamaoncol.2024.1549.
Shaver AL, Nikita N, Sharma S, et al. The safety of abiraterone acetate in patients with metastatic castration-resistant prostate cancer: an individual-participant data meta-analysis based on 14 randomized clinical trials. Cancers (Basel). 2025;17(17):2747. doi:10.3390/cancers17172747.
Kent DM, Paulus JK, van Klaveren D, et al. The Predictive Approaches to Treatment effect Heterogeneity (PATH) statement. Ann Intern Med. 2020;172(1):35-45. doi:10.7326/M18-3667.
Kent DM, Steyerberg E, van Klaveren D. Personalized evidence based medicine: predictive approaches to heterogeneous treatment effects. BMJ. 2018;363:k4245. doi:10.1136/bmj.k4245.
YODA Project. Association between baseline cardiovascular risk and cardiovascular effect of abiraterone acetate in advanced prostate cancer (Protocol 2025-0040). Accessed July 28, 2026. https://yoda.yale.edu/data-request/2025-0040/
Royston P, Parmar MKB. Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome. BMC Med Res Methodol. 2013;13:152. doi:10.1186/1471-2288-13-152.
Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385(19):1737-1749. doi:10.1056/NEJMoa2102953.
Burke DL, Ensor J, Riley RD. Meta-analysis using individual participant data: one-stage and two-stage approaches, and why they may differ. Stat Med. 2017;36(5):855-875. doi:10.1002/sim.7141.
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496-509. doi:10.1080/01621459.1999.10474144.
van Buuren S, Groothuis-Oudshoorn K. mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1-67. doi:10.18637/jss.v045.i03.
Stewart LA, Clarke M, Rovers M, et al. Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD statement. JAMA. 2015;313(16):1657-1665. doi:10.1001/jama.2015.3656.

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