<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">OJS</journal-id><journal-title-group><journal-title>Open Journal of Statistics</journal-title></journal-title-group><issn pub-type="epub">2161-718X</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/ojs.2013.31003</article-id><article-id pub-id-type="publisher-id">OJS-27915</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Physics&amp;Mathematics</subject></subj-group></article-categories><title-group><article-title>
 
 
  Quantile Regression Based on Semi-Competing Risks Data
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>in-Jian</surname><given-names>Hsieh</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>A.</surname><given-names>Adam Ding</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Weijing</surname><given-names>Wang</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Yu-Lin</surname><given-names>Chi</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>Department of Mathematics, National Chung Cheng University, Chia-Yi, Chinese Taipei</addr-line></aff><aff id="aff2"><addr-line>Department of Mathematics, Northeastern University, Boston, USA.</addr-line></aff><aff id="aff3"><addr-line>Institute of Statistics, National Chiao-Tung University, Hsin-Chu, Chinese Taipei</addr-line></aff><author-notes><corresp id="cor1">* E-mail:<email>jjhsieh@math.ccu.edu.tw(IH)</email>;<email>ding@neu.edu,(AAD)</email>;<email>wjwang@stat.nctu.edu.tw(WW)</email>;</corresp></author-notes><pub-date pub-type="epub"><day>20</day><month>02</month><year>2013</year></pub-date><volume>03</volume><issue>01</issue><fpage>12</fpage><lpage>26</lpage><history><date date-type="received"><day>December</day>	<month>7,</month>	<year>2012</year></date><date date-type="rev-recd"><day>January</day>	<month>10,</month>	<year>2013</year>	</date><date date-type="accepted"><day>January</day>	<month>22,</month>	<year>2013</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
   This paper considers quantile regression analysis based on semi-competing risks data in which a non-terminal event may be dependently censored by a terminal event. The major interest is the covariate effects on the quantile of the non-terminal event time. Dependent censoring is handled by assuming that the joint distribution of the two event times follows a parametric copula model with unspecified marginal distributions. The technique of inverse probability weighting (IPW) is adopted to adjust for the selection bias. Large-sample properties of the proposed estimator are derived and a model diagnostic procedure is developed to check the adequacy of the model assumption. Simulation results show that the proposed estimator performs well. For illustrative purposes, our method is applied to analyze the bone marrow transplant data in [1].
     
 
</p></abstract><kwd-group><kwd>Copula Model; Dependent Censoring; Quantile Regression; Semi-Competing Risks Data</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>Quantile regression analysis has received increasing attentions in the recent literature of survival analysis. Compared with conventional regression models such as the proportional hazards (PH) model or the accelerated failure time (AFT) model, quantile regression models provide direct assessment of the covariate effect on different quantiles of the failure time variable. This model also allows covariates to affect both location and shape of the distribution. Let T be the failure time of interest, <img src="3-1240171\5af5d079-7b33-4486-94dc-c7f668754348.jpg" />be a <img src="3-1240171\14f2533b-7145-4227-a1c6-e74b492d87e5.jpg" /> vector and<img src="3-1240171\1058a8ae-e2b1-45f3-8a47-251193a94b82.jpg" />. Consider the following linear quantile regression model on<img src="3-1240171\58648cfb-7611-475b-b440-8e7881aa5708.jpg" />, where <img src="3-1240171\875a4edc-f86a-44e7-a027-bf5307dca681.jpg" /> is a known monotonic function, such that</p><disp-formula id="scirp.27915-formula74071"><label>(1)</label><graphic position="anchor" xlink:href="3-1240171\9174f682-3b40-4834-af63-82bc2b26c72f.jpg"  xlink:type="simple"/></disp-formula><p>where <img src="3-1240171\fd22db35-7dc6-4649-8feb-566588582bf2.jpg" /> and <img src="3-1240171\d2f9eeae-dc3d-4139-972a-0b8afab7a37a.jpg" /> is the <img src="3-1240171\aa2a63e5-8002-4ce7-b3ee-86708e732ada.jpg" />th quantile of Y conditional on Z. Note that when we set<img src="3-1240171\a0c2922a-202d-4111-aa72-e9f73d1645f9.jpg" />, model (1) is equivalent to <img src="3-1240171\7d4c6636-1471-41a0-a661-e69054f3703d.jpg" />. Many papers for estimating <img src="3-1240171\c7422a93-bd72-45e4-bce9-154dfd7e2f18.jpg" /> without specifying the distribution of <img src="3-1240171\f0f5a75e-083b-4e38-a693-40cf3e1b1906.jpg" /> or <img src="3-1240171\f33a46bb-b49b-49b9-89ff-7db58dd9fa1b.jpg" /> have appeared in the literature. [2-5] considered quantile regression analysis under a fixed censoring mechanism in which all the censoring times are observed. Independent right censorship has been assumed by many papers including [6-11].</p><p>In this paper, we consider semi-competing risks data [<xref ref-type="bibr" rid="scirp.27915-ref12">12</xref>] in which the failure time of a non-terminal event T is subject to dependent censoring by a terminal event time D but not vice versa. Consider an example of bone marrow transplantation for leukemia patients described in [<xref ref-type="bibr" rid="scirp.27915-ref1">1</xref>] such that T is the time to leukemia relapse and D is the time to death. One important risk factor is the disease classification (i.e. ALL, AML low-risk, and AML highrisk) which was determined based on patient’s status at the time of transplantation. Here we assume that T, the time to a non-terminal event, follows model (1). Note that [13,14] also considered quantile regression analysis for competing risks data and left-truncated semi-competing risks data respectively. They defined the quantiles based on the crude quantity, namely the cumulative incidence function<img src="3-1240171\30dd48c9-f719-441f-bb15-3529a99360dc.jpg" />. In contrast, the proposed regression model (1) is defined based on the net quantity <img src="3-1240171\8a73b204-c6d8-4ebc-a0e9-f965953515a4.jpg" /> which is not identifiable without extra assumption on the dependence structure. There has been some controversy over which quantity should be used in presence of dependent competing risks. We believe that both quantities are important and not mutually exclusive as they provide information on different aspects of the data. Here <img src="3-1240171\7b2f67f4-2ed4-41be-a5b4-44e5a2465982.jpg" /> measures the covariate effect on T after separating the potential influence from D. Such analysis is also useful in practical applications. For example, a covariate may prolong D so that increase <img src="3-1240171\767515c9-ce32-40a7-be18-a6e6559b637f.jpg" /> but have no direct effect on the nonterminal event. The dependence between T and D complicates the estimation of<img src="3-1240171\3a9fdd94-85f8-4f44-9c8c-a2a39a368ae4.jpg" />. We will adopt a semi-parametric copula assumption to model their joint distribution and apply the technique of inverse probability weighting (IPW) to correct the bias due to dependent censoring in the estimation procedure. The association parameter in the copula model will also be estimated using existing methods.</p><p>The rest of this paper is organized as follows. In Section 2, we introduce the data structure and model assumptions. The proposed methodology for parameter estimation and model checking is presented in Section 3. The proofs of the asymptotic properties are given in the Appendix. Section 4 contains simulation results. In Section 5, we apply the proposed methods to analyze the bone marrow transplant data in [<xref ref-type="bibr" rid="scirp.27915-ref1">1</xref>] and in Section 6, we give some concluding remarks.</p></sec><sec id="s2"><title>2. Data and Model Assumptions</title><p>Recall that T and D denote the time to a non-terminal event and the time to a terminal event respectively such that T is subject to censoring by D but not vice versa. In presence of additional external censoring due to drop-out or the end-of-study effect, one observes <img src="3-1240171\e79fbbb1-f534-4007-8392-e46afb9dad00.jpg" /> such that<img src="3-1240171\40cd5da9-b20d-4e32-bf23-f408cc8f2f70.jpg" />, <img src="3-1240171\fdbae922-b18c-4d3e-b9df-ffee37a57bd2.jpg" />, <img src="3-1240171\62851819-940f-47e7-9fdd-d67289c136ab.jpg" />, <img src="3-1240171\4a8aa1c6-c867-4dab-ad5e-dbb18063e455.jpg" />, where <img src="3-1240171\bad00caa-261e-4fae-bd50-660b24a3a92d.jpg" /> is the minimum operator and <img src="3-1240171\49f97ee2-ca7a-4146-b9a1-7ce1ab69be2a.jpg" /> is the indicator function. The covariate vectors can be denoted as <img src="3-1240171\fe15918f-e6da-4de6-bb93-66009bd1ed24.jpg" /> and<img src="3-1240171\87a92cd4-ff2c-424a-8d2c-48037ce959ee.jpg" />. The sample Contains <img src="3-1240171\e4aa8b1c-e641-40bf-b042-f56b390919eb.jpg" /> which are random replications of<img src="3-1240171\ec8cc1c5-82d4-4ca9-bb51-2e3fed5356ed.jpg" />. We will assume that <img src="3-1240171\8138d5d8-2884-4d9d-951b-700c5baff5a0.jpg" /> and C are independent given Z. The covariate effect on T is specified by model (1) and the major objective is to estimate <img src="3-1240171\3ce6e26e-b7bb-4ef1-b21a-0a65f1213acc.jpg" /> based on semi-competing risks data.</p><p>To handle dependent censoring, we have to make extra assumptions about the dependence structure between T and D in the upper wedge. According to [<xref ref-type="bibr" rid="scirp.27915-ref15">15</xref>] who extended Sklar’s theorem to the regression setting, we consider the following copula model</p><disp-formula id="scirp.27915-formula74072"><label>(2)</label><graphic position="anchor" xlink:href="3-1240171\d1e6346f-f9f1-422c-87d7-0bb40fca3699.jpg"  xlink:type="simple"/></disp-formula><p>where<img src="3-1240171\2ec1bb8a-debc-4f09-9369-db8ad19abbe5.jpg" />,<img src="3-1240171\21e6125f-fc5f-4330-bc0b-ffc29df33fd0.jpg" /> and <img src="3-1240171\6583d37a-7a93-458a-9851-88ae65a9d0c3.jpg" /> are the marginal survival functions of T and D, given<img src="3-1240171\c0efd082-0adf-4725-8c75-e0f32ae24e75.jpg" />, and <img src="3-1240171\f17d3d9c-73d5-4289-9566-d981dc5d4e00.jpg" /> is a parametric copula function defined on the unit square. The association parameter <img src="3-1240171\e6f41ce9-3757-4412-9b01-363ead69c5b3.jpg" /> in (2) is related to Kendall’s tau defined by</p><p><img src="3-1240171\cc7c5fa2-e1cc-4ed8-8150-91f3df9c55f3.jpg" /></p><p>In particular, we will assume <img src="3-1240171\a7a3c29a-ad90-4c86-b17b-31c517274987.jpg" /> in the upper wedge follows a popular subclass of copula models, namely Archimedean copula (AC), in which the copula function can be further expressed as</p><disp-formula id="scirp.27915-formula74073"><label>(3)</label><graphic position="anchor" xlink:href="3-1240171\e5589d28-d011-4ac5-aa78-f7bb555a5273.jpg"  xlink:type="simple"/></disp-formula><p>where <img src="3-1240171\0319ecc3-4b01-4348-8daa-96863a4a69ba.jpg" /> is a non-increasing convex function defined on <img src="3-1240171\7483039e-ed04-4eb2-8d3e-36d1dbebb691.jpg" /> with<img src="3-1240171\eca152e7-0a9c-4a46-bd28-55ff93707729.jpg" />. Examples of Archimedean copula include Clayton’s copula with</p><p><img src="3-1240171\2643d29f-e9c0-40e4-a07e-6e7d6e07cd0a.jpg" /></p><p>and</p><p><img src="3-1240171\f3f58a2e-231a-4dfd-8210-10e29610f575.jpg" />;</p><p>and Frank’s copula with</p><p><img src="3-1240171\abfd51d7-cd2f-4616-a9ee-3f4ff5d608de.jpg" /></p><p>and</p><p><img src="3-1240171\1e7087f5-a570-4600-ad76-2762cbc58eff.jpg" />.</p></sec><sec id="s3"><title>3. The Proposed Inference Methods</title><p>Our major objective is to develop an inference method for estimation <img src="3-1240171\84a37280-4200-432a-836f-624b111af1a1.jpg" /> but, in the mean time, employ existing methods for estimating <img src="3-1240171\bdbe5f8f-048b-4e73-9b3e-ae9dbafc77fd.jpg" /> based on semicompeting risks data such as those proposed by [<xref ref-type="bibr" rid="scirp.27915-ref16">16</xref>] and [<xref ref-type="bibr" rid="scirp.27915-ref17">17</xref>].</p><sec id="s3_1"><title>3.1. Estimation of <img src="3-1240171\00f53ee0-7572-4759-a2f3-488d8211766c.jpg" /> for Discrete Covariates</title><p>In absence of censoring, one can estimate <img src="3-1240171\1c3b6585-2ba2-4b4c-94f9-eb51c41d1b4d.jpg" /> by solving</p><p><img src="3-1240171\aeec6461-b239-4e46-9806-3c3c39e3a910.jpg" /></p><p>Since <img src="3-1240171\e476fd31-c0d5-45da-8686-c263bfad58c9.jpg" /> is subject to censoring by<img src="3-1240171\c0371da2-1639-4978-ba74-4c14ba8697f9.jpg" />, it follows that</p><p><img src="3-1240171\28455541-6217-4824-8c4c-a768d171c006.jpg" /></p><p>where the reciprocal of the weight function is given by</p><p><img src="3-1240171\ef701c04-cc71-419e-9d28-4150a2eab440.jpg" /></p><p>The above derivations yield the following estimating function for <img src="3-1240171\4c17561e-d7f3-405a-b070-7c2324cfb575.jpg" /></p><p><img src="3-1240171\778a36df-c66e-4f4c-b709-48cf784acbf3.jpg" /></p><p>This is the so called inverse probability weighting technique for bias correction. Since <img src="3-1240171\fe6a9cf5-9d84-45b1-8fbd-248d4b5ee4f0.jpg" /> needs to be estimated, it is natural to modify the estimating equation as</p><disp-formula id="scirp.27915-formula74074"><label>(4)</label><graphic position="anchor" xlink:href="3-1240171\3972f0a5-ad54-4a56-a744-145f69d8554a.jpg"  xlink:type="simple"/></disp-formula><p>where the estimated components in the weight can be denoted as</p><p><img src="3-1240171\5d57ee98-5307-4f4d-a660-8b1d7e99564a.jpg" /></p><p>Now we discuss estimation of the weight components. We will first address the situation that Z takes discrete values, and then briefly discuss possible modification for continuous covariates. Since <img src="3-1240171\50fb3c9a-b534-4ef4-a731-81f34faa0d3f.jpg" /> is independent of T and D given Z, <img src="3-1240171\c4446874-1711-46a7-9c32-26849193c7e4.jpg" />can be estimated by the Kaplan-Meier estimator based on data</p><p><img src="3-1240171\6fffb21d-42de-458c-8387-d210f216a2b0.jpg" />or <img src="3-1240171\1b1ad5a2-b881-43e8-8614-5bae4801a588.jpg" /></p><p>with<img src="3-1240171\69106851-a2c5-4565-97b0-b911d28d5829.jpg" />. We will utilize some analytic properties of the chosen AC model to derive an explicit expression of<img src="3-1240171\4b7e0815-c9ea-437f-b4f7-4097cf8bc8b4.jpg" />. Denote<img src="3-1240171\6a850544-8e7f-4bd2-a476-39aa5badbe36.jpg" />,</p><p><img src="3-1240171\f59b976a-3146-4bbe-93a5-85158d5cf3bb.jpg" />and</p><p><img src="3-1240171\226e03f0-12a9-426a-a7d4-db5fd105662d.jpg" />. It follows that</p><p><img src="3-1240171\63373187-d32b-484d-a1a2-c937655f5e2f.jpg" /></p><p>We suggest to estimate <img src="3-1240171\6dd5a30a-dab6-4ad1-a981-f2494425ecc0.jpg" /> by applying the estimators in [<xref ref-type="bibr" rid="scirp.27915-ref17">17</xref>] for quantities in the right-hand side of the above expression. Specifically <img src="3-1240171\55a6eaf7-6bfd-4e9b-a0d8-340e089a7c54.jpg" /> is the Kaplan-Meier estimator of <img src="3-1240171\902140e9-4a96-4f7f-8b03-13229b2805c2.jpg" /> based on</p><p><img src="3-1240171\58fa1bdf-d700-4d90-8f5a-c13e8bb64d34.jpg" />, where<img src="3-1240171\13181f3c-1a5a-43f7-a5ce-9c16b105036b.jpg" />,</p><p><img src="3-1240171\83d5433e-3f1a-4465-a9cf-67912cbd656c.jpg" />is the copula-graphic estimator</p><p><img src="3-1240171\c40ad784-42c1-4325-87a6-26073afe9ff0.jpg" /></p><p>where the estimator <img src="3-1240171\173fbded-3c9e-4db3-b424-c5f867410a95.jpg" /> is the root of the following estimating equation,</p><p><img src="3-1240171\c74265b8-317a-4e5b-ab02-9c4d8e6e0fcf.jpg" /></p><p>where<img src="3-1240171\13a3fbc3-08d4-4b40-8822-4ccebcea222d.jpg" />, <img src="3-1240171\7e4f5d27-6cd3-4fe0-b45c-39860c3b89aa.jpg" />, <img src="3-1240171\19c5948b-3121-483f-86a7-bafb9c84b3d0.jpg" />,</p><p><img src="3-1240171\a0392a9b-d471-4982-9048-6b2ac84d5fa8.jpg" />, <img src="3-1240171\a47918c8-cd2d-4902-88b7-1e9c66b2ffa7.jpg" />, <img src="3-1240171\3dc4bffc-458f-4bb5-8491-810af111981a.jpg" />is a weight function, <img src="3-1240171\272e73eb-6ecc-48eb-aa43-98fe2d544e6b.jpg" />, and</p><p><img src="3-1240171\fd5573e3-9a51-4d21-8e25-8073910bbcb8.jpg" /></p><p>where<img src="3-1240171\b191466c-ce76-4e0a-89b8-67c8a3124d48.jpg" />. Then</p><disp-formula id="scirp.27915-formula74075"><label>(5)</label><graphic position="anchor" xlink:href="3-1240171\c993d840-d29f-44aa-8df2-cd1a397c8c72.jpg"  xlink:type="simple"/></disp-formula><p>This estimator is then used in estimating Equation (4).</p><p>The Equation (4) may not be continuous so that an exact solution may not exist. Here we define <img src="3-1240171\44fb7893-6c2c-4d29-9afb-ca30443e47ec.jpg" /> as a generalized solution as in [13,18]. By the monotonic property of (4), the set of generalized solutions is convex. Using the arguments in [<xref ref-type="bibr" rid="scirp.27915-ref13">13</xref>], the solution of (4) can be reformulated as the minimizer of the following function,</p><p><img src="3-1240171\bbd88c97-6fee-43fb-8108-7daa8953f6ce.jpg" /></p><p>where M is a large enough positive value to bound</p><p><img src="3-1240171\f629d504-0591-40fb-a34b-3527495f8c75.jpg" />and <img src="3-1240171\e7c41d14-8624-4ab0-b66d-1b91ee7c916d.jpg" /> from above.</p><p>We suggest using a re-sampling approach for variance estimation since the analytic formula for the variance of <img src="3-1240171\4676a6d0-46c2-40ad-86d7-ab574f1ed960.jpg" /> is complicated to calculate. Based on the nonparametric bootstrap approach, we can sample replications <img src="3-1240171\c30b324b-950d-4c5f-a03f-b4c7f2c0a184.jpg" /> from the original data. Given a bootstrap sample, we can compute<img src="3-1240171\2161bfb6-e62f-4889-9796-214acc31c356.jpg" />. Repeating the re-sampling procedure B times, we obtain</p><p><img src="3-1240171\ba7f3e7c-5b7d-4787-92b7-b20808ac05f9.jpg" />and the variance of <img src="3-1240171\cc2cfc2c-e500-43cd-8cd6-81acfe463b6d.jpg" /> can be estimated by</p><p><img src="3-1240171\42dac5e8-f0d8-4f87-8427-e954438aad08.jpg" /></p><p>where<img src="3-1240171\d788e9f6-86c5-42a9-aa0b-fc3d3e2b36da.jpg" />. Furthermore, we can construct the <img src="3-1240171\29ad7d0a-2a7c-4fab-8d57-55b2b0a95fe8.jpg" /> confidence interval for <img src="3-1240171\5806874f-91da-4b19-b01d-f3b70150ae67.jpg" /> as</p><p><img src="3-1240171\4d3cd6f1-46c8-4a87-9f01-6d1fa169f778.jpg" />, where<img src="3-1240171\d5694077-7743-45a5-80fb-ae2dbb3d3de1.jpg" />, and <img src="3-1240171\e94b57ed-d992-4ab0-bc87-13e3e9a0ea08.jpg" /></p><p>is the cumulative distribution function of a standard normal random variable. The bootstrap percentile method suggests another way of constructing a <img src="3-1240171\cec346e4-1151-43f5-bbc2-d0c8d3bd564a.jpg" /> confidence interval of <img src="3-1240171\b550a89e-1a40-4e09-9727-e0c1ce3449ab.jpg" /> with the formula</p><p><img src="3-1240171\8a5be11c-4f9b-42df-adde-d871520bb52b.jpg" />, where<img src="3-1240171\7bf1b210-ad67-4147-b22f-f128bdb1fb1a.jpg" />, <img src="3-1240171\1db822ea-6a8b-4a98-83f5-32493dac9d2f.jpg" /></p><p>are the order statistics of <img src="3-1240171\ebb9b2d5-645b-44ac-b51e-73314f9e43ec.jpg" /> for<img src="3-1240171\354b768f-7814-4232-adb2-768a5cec09d6.jpg" />.</p></sec><sec id="s3_2"><title>3.2. Asymptotic Properties for Discrete Covariates</title><p>We establish the uniform consistency and weak convergence of the proposed estimator <img src="3-1240171\fda74910-7fc1-4027-a7b6-c4237f775aaa.jpg" /> for<img src="3-1240171\827fcaf8-63f4-4b53-b93f-cc34114589cd.jpg" />, a region that <img src="3-1240171\50ea51db-0a7d-4041-aaa6-461358bd9189.jpg" /> is identifiable. We first state the regularity conditions.</p><p>(C1) Denote the set of possible covariate Z values as <img src="3-1240171\f7d8023c-fa10-4795-8447-b6024b4ce3d6.jpg" /> which is a compact set in<img src="3-1240171\3edf9eb4-905c-4c93-8c7a-9e2743af13ca.jpg" />. The probability density function <img src="3-1240171\58ace159-1877-4bb8-b458-cee59184ce54.jpg" /> for covariate Z is uniformly bounded above and below on<img src="3-1240171\6313b4c5-a94b-440c-96e5-e798514665cb.jpg" />.</p><p>(C2) There exists a compact set <img src="3-1240171\f938a929-7550-4dd6-be6e-20ebeb424b61.jpg" /> in the parameter space for the copula parameter <img src="3-1240171\d7e6fc33-51a8-4cf6-82cd-20c2813db9b8.jpg" /> such that all true values of <img src="3-1240171\84b7df24-0947-4ca1-baf2-bc485c842fb3.jpg" /> are interior points of <img src="3-1240171\33c26f25-915c-45d0-bab9-9fb51db2378d.jpg" /> for all<img src="3-1240171\8aa11c3a-4ab2-41fb-8ec4-752ace72b090.jpg" />.</p><p>(C3) There exists <img src="3-1240171\894b1af3-9bae-4866-ac03-7baeb3cd4b66.jpg" /> such that<img src="3-1240171\fdff91d4-743b-44c5-aadc-1e7a32211d93.jpg" />, <img src="3-1240171\82b7b749-1ace-477e-9317-7ed952c283ef.jpg" />, <img src="3-1240171\5836ab65-c62f-4988-8b5a-a3ddcc5fb9b5.jpg" />and</p><p><img src="3-1240171\2081b752-f14d-4154-9647-4684edc7e815.jpg" />.</p><p>(C4) 1) <img src="3-1240171\0774cd85-061f-435e-86ff-514c35ac9a81.jpg" />is Lipschitz continuous for<img src="3-1240171\4f3a7338-398a-46f3-b472-fe2c4784eb0b.jpg" />;</p><p>2) The density <img src="3-1240171\a77ca887-6b92-4903-af4a-bc3f5023f17e.jpg" /> is bounded above uniformly for <img src="3-1240171\e116a763-d180-47ab-b107-c08a19642ae2.jpg" /> and<img src="3-1240171\90ed7681-8c1a-498f-8629-86c5d0bdfa5b.jpg" />; 3) The copula generator function <img src="3-1240171\00704187-5975-4d05-8950-9e26c950f0cc.jpg" /> has continuous derivatives<img src="3-1240171\2c7f798b-e6dc-4e32-8d2e-c377f0ec2ff4.jpg" />,</p><p><img src="3-1240171\221c7db5-c544-40b5-b38c-05f9db80f973.jpg" />, <img src="3-1240171\f7a3f829-8d6a-490b-a981-e8676efe6727.jpg" />, <img src="3-1240171\7a782b80-c412-42e7-ac31-8b91ac6ffe36.jpg" />and <img src="3-1240171\bc12cf07-19e6-45e7-8e19-f2f89f6ab770.jpg" /> which do not equal 0 for all <img src="3-1240171\c9a37ec8-c8e5-4735-8adb-113d1cb64b38.jpg" /> and<img src="3-1240171\778f1f1a-46d7-4bd9-80e9-a577bad75035.jpg" />.</p><p>(C5) <img src="3-1240171\25d2b5f6-6b37-42a7-9d6d-358f37d10496.jpg" />eigmin<img src="3-1240171\923194c5-3312-4905-81d2-c1f9c5584658.jpg" />, for some <img src="3-1240171\cc628369-5b88-47d4-a2d0-861a44a0ff9f.jpg" /></p><p>and<img src="3-1240171\0a0ac8b1-416c-4df5-b0b6-d4eafa4ab869.jpg" />, where<img src="3-1240171\70e63eca-218b-49de-848f-b7fdfc4f6ab5.jpg" />,</p><p><img src="3-1240171\11bc16d8-57c9-4b8b-85f7-6087aa2d0a31.jpg" />and <img src="3-1240171\c8e60134-4a0c-4386-bdfe-af8666dc8b8b.jpg" /> for a vector u.</p><p>Condition C1 assumes the boundedness of covariates and is satisfied for finite discrete covariates. This assumption is only used to derive the asymptotic properties of <img src="3-1240171\25f6a41e-cae8-4478-ab39-a0f40ce7ed81.jpg" /> for proving Theorem 1. Condition C2 assumes that the true value of <img src="3-1240171\4be6007d-b97a-409c-aca4-839a48056543.jpg" /> is an interior point in the parameter space which is a common regularity condition. Condition C3 is assumed to simplify theoretical arguments similar to condition C1 in [<xref ref-type="bibr" rid="scirp.27915-ref13">13</xref>], and generally <img src="3-1240171\76a80b57-3264-42a2-8048-bc51884b9201.jpg" /> is the study end time in practical applications. Conditions C4 1) and 2) assume the smoothness of coefficient processes, and the uniform boundedness on the density of T, which are standard for quantile regression methods. Condition C4 3) imposes the smoothness requirement on the copula generator function similar to the regularity conditions in [17,19]. Condition C5 is similar to condition C4 in [<xref ref-type="bibr" rid="scirp.27915-ref13">13</xref>] which ensures the identifiability of <img src="3-1240171\99359d4c-4d5f-491c-9a88-4489772f25ac.jpg" /> and is needed for proving the consistency of<img src="3-1240171\9e5eef1f-260a-40af-9f67-53eb76a42c22.jpg" />.</p><p>Therefore with finite<img src="3-1240171\a852492f-9f3d-4487-8a9f-029780c287e4.jpg" />, we prove the following result.</p><p>Theorem 1 If conditions C1-C5 hold, then</p><p><img src="3-1240171\b6047376-f7be-465a-ba4a-fa3771b18811.jpg" />and <img src="3-1240171\8c622157-9946-48ee-9dd3-c375cb4a640b.jpg" /> converges weakly to a meanzero Gaussian process.</p><p>The detailed proofs are presented in the Appendix.</p></sec><sec id="s3_3"><title>3.3. Model Checking and Model Diagnosis</title><p>Motivated by the work of [20-22] in which complete data are considered, we define the residual quantities as</p><p><img src="3-1240171\171ab823-c5de-4d1f-87a8-34011814abbd.jpg" /></p><p>for <img src="3-1240171\0ecc1758-a1e7-4c1e-8770-1d7245c903e9.jpg" /> and consider</p><p><img src="3-1240171\c74afeee-43fd-4a59-9f39-16263bf032dc.jpg" /></p><p>where <img src="3-1240171\27cc723e-f41a-49c6-82cd-ae5cb901a09c.jpg" /> is a known bounded weight function. Similar to the arguments in [13,23], <img src="3-1240171\9515cb01-38bd-47f4-95ec-f200bc97920e.jpg" />converges weakly to a zero-mean Gaussian process if model (1) is specified correctly and the covariate takes discrete values. Therefore we propose the following test statistic</p><p><img src="3-1240171\39f586f2-94fa-430d-a234-08c54b001e61.jpg" /></p><p>where <img src="3-1240171\ab876edd-4eda-4e23-b91b-e4e2615a073d.jpg" /> is an estimator of the standard deviation of <img src="3-1240171\dfe95554-7a7e-4712-bbe3-96b96a3dc610.jpg" /> which can be obtained by applying the bootstrap approach mentioned earlier. Thus, we have that T<sub>n</sub> converges to the standard normal random variable asymptotically as the model is correct. On the other hand, when the model is mis-specified, T<sub>n</sub> will deviate from zero. Accordingly we can reject the model assumption if<img src="3-1240171\c46af173-c5f7-4f32-8cc5-a92d900bc978.jpg" />, where <img src="3-1240171\60d3c2b8-5418-48d9-85c4-727fc53edde9.jpg" /> is the quantile of <img src="3-1240171\6eca695b-aab4-40a9-9c74-faf3a3cee7db.jpg" /> and <img src="3-1240171\ee906772-2014-407f-aa59-7a67620fb6fc.jpg" /> is the level of significance. If there are K candidate models under consideration, we compute the absolute value of T<sub>n</sub> for each model for <img src="3-1240171\6c1fc1f8-46d4-4abc-91a7-280cbaf03229.jpg" /> and choose the one with the smallest value.</p></sec><sec id="s3_4"><title>3.4. Estimation for Continuous Covariates</title><p>We briefly discuss how to extend our estimation method for continuous covariates. One can apply a smoothing approach to estimate the probability functions conditional on z. Following [<xref ref-type="bibr" rid="scirp.27915-ref24">24</xref>], without loss of generality, assume that <img src="3-1240171\7a384855-9b69-4768-b445-a9e1f6889506.jpg" /> and <img src="3-1240171\67e1f254-2763-4de0-a5ac-04fc3130ddde.jpg" /> are ordered. Let</p><p><img src="3-1240171\3c79e65f-9f46-4d15-ae01-cedb5f7324d8.jpg" /></p><p>where<img src="3-1240171\eafa43b6-2d95-4435-a5d4-10e8c26adb58.jpg" />, <img src="3-1240171\b104964d-4af2-4c9f-8f30-6a7601963f41.jpg" />is the bandwidth and <img src="3-1240171\8d401ec7-900b-4373-9f3d-a8f0b07fce62.jpg" /> is the kernel. Then</p><p><img src="3-1240171\9ad0e3aa-d924-49df-ab90-8aae11599b3d.jpg" /></p><p>where <img src="3-1240171\1300bd6b-45c7-40d8-b813-2332e283050f.jpg" /> are the rearrangement <img src="3-1240171\f3a4b9a3-bf5b-4b9b-bd43-f8c06acad98e.jpg" /> sorted according to W<sub>i</sub>, where <img src="3-1240171\5342ab0d-19bd-4ab8-9f96-453f4789b287.jpg" /> and</p><p><img src="3-1240171\ef886e15-30bf-4e68-b079-b9d5c7432cc5.jpg" />, and <img src="3-1240171\eb380c66-1d80-4761-a2ef-02912cf38c35.jpg" /> is the copula-graphic estimator in [<xref ref-type="bibr" rid="scirp.27915-ref24">24</xref>]</p><disp-formula id="scirp.27915-formula74076"><label>(6)</label><graphic position="anchor" xlink:href="3-1240171\bf562ba1-196c-4448-ab16-660f77774b5a.jpg"  xlink:type="simple"/></disp-formula><p>and <img src="3-1240171\4acee060-ff66-4d01-929c-7c0c55de22ff.jpg" /> solves estimating equation</p><p><img src="3-1240171\7b26eca2-f1b5-4d58-a672-a2b4dcad0742.jpg" /></p><p>Special techniques are needed to derive the asymptotic properties for the case of continuous covariates. For example properties of the smoothed versions of <img src="3-1240171\3d304d6e-03fc-4eff-9996-08f355ac76a9.jpg" /> and <img src="3-1240171\152c26fd-9fde-4aff-98c8-fd9883c72636.jpg" /> are not fully available yet. The <img src="3-1240171\65033329-d91c-4432-abbf-9101fa9c9486.jpg" /> convergence rate for the normality proof may not be directly extended since the smooth version of <img src="3-1240171\0fff1ee8-c907-4681-9678-5e1e45829d4a.jpg" /> may not be <img src="3-1240171\0341185e-9213-469b-96b0-6db0c362d734.jpg" /> asymptotic normal. However the estimator for the quantile regression parameter may still be <img src="3-1240171\b262695e-57bb-4701-b48c-d32722ed6ae8.jpg" /> asymptotic normal even when some component converges at a slower rate.</p></sec></sec><sec id="s4"><title>4. Simulation Studies</title><p>We conduct simulation studies to examine the finitesample performance of the proposed methods with R software. Here we consider two cases. For the first one, we consider the model,</p><disp-formula id="scirp.27915-formula74077"><label>(7)</label><graphic position="anchor" xlink:href="3-1240171\4fd22fe8-0357-4599-a3ca-10496c35ff1d.jpg"  xlink:type="simple"/></disp-formula><p>where <img src="3-1240171\fd46fef1-0734-42c4-b48c-ba0eb82cc077.jpg" /> and<img src="3-1240171\cf2dbcff-9fde-4e62-a456-703c9a1f280d.jpg" />. We generate <img src="3-1240171\7b633728-e7be-497e-846e-0bb9714dbe47.jpg" /> which follow the Clayton copula and Frank copula with <img src="3-1240171\b8e5f452-e007-47a2-8d3a-f17971dfdaeb.jpg" /> marginally following <img src="3-1240171\9d4d6056-dafd-4aef-b689-a7bb640e7ae5.jpg" /> so that<img src="3-1240171\e35e0884-d146-4bf7-a56e-f982c8423856.jpg" />, and D marginally following exp(2). For the second case, we consider</p><disp-formula id="scirp.27915-formula74078"><label>(8)</label><graphic position="anchor" xlink:href="3-1240171\12fc6041-3273-40bc-a1b5-67b62d12ce6b.jpg"  xlink:type="simple"/></disp-formula><p>where<img src="3-1240171\3f6b967f-54c1-4110-8318-07a07bb49f5b.jpg" />, <img src="3-1240171\282eb533-6981-400a-bf6a-9f7e534be369.jpg" />and <img src="3-1240171\39ea6477-1051-425c-93f2-718be0348405.jpg" /> generated from the Clayton copula and Frank copula with <img src="3-1240171\b5b007e9-6eaf-408b-81e2-b8b1c0abe6c1.jpg" /> following <img src="3-1240171\87c1e045-79a7-4e6b-b7f6-8aeb369d885b.jpg" /> and<img src="3-1240171\d9b104a1-1965-4629-bb19-1f5694e76079.jpg" />. In this case,<img src="3-1240171\70978e59-e840-46c0-b233-a5b21e806138.jpg" />. Three levels of association τ = 0.3, 0.5, 0.7 are considered. The censoring variable C follows a uniform distribution on<img src="3-1240171\d1cf725f-584c-4a64-8858-1531303d623f.jpg" />.</p><p>We evaluate the performances for γ = 0.1, 0.3, 0.5 and the sample size n = 100 based on 400 simulation runs. To obtain the standard error of the proposed estimator, we use the bootstrap method with B = 50. Based on the settings, we also present a naive estimator of<img src="3-1240171\f4671cdb-6229-4a29-a614-9681f15bf5ba.jpg" />, which is constructed under the wrong assumption that T is independently censored by<img src="3-1240171\c06ef3e2-f78c-4263-b58e-1109a93112ef.jpg" />. That is, we estimate <img src="3-1240171\657e73d8-049e-4411-8c9b-65a64f84f78f.jpg" /> by solving the estimating Equation (4) with</p><p><img src="3-1240171\e3161ba2-9c8c-45d2-a98e-12d0bbe1e912.jpg" /></p><p>Tables 1-4 report the average bias of the proposed</p><p><xref ref-type="table" rid="table1">Table 1</xref>. Finite-sample results for estimating the quantile regression parameters under model (7) with Clayton copula.</p><p><img src="3-1240171\9b046c47-55db-4b55-b86a-e65452f078cf.jpg" /></p><p>The results are based on 400 simulation runs each with a sample size 100.</p><p><xref ref-type="table" rid="table2">Table 2</xref>. Finite-sample results for estimating the quantile regression parameters under model (8) with Clayton copula.</p><p><img src="3-1240171\3fd02930-ec21-49b6-b2f6-acc49ed1035f.jpg" /></p><p>The results are based on 400 simulation runs each with a sample size 100.</p><p><xref ref-type="table" rid="table3">Table 3</xref>. Finite-sample results for estimating the quantile regression parameters under model (7) with Frank copula.</p><p><img src="3-1240171\d5c674e9-1601-477a-9a31-1b9e7df705fa.jpg" /></p><p>The results are based on 400 simulation runs each with a sample size 100.</p><p><xref ref-type="table" rid="table4">Table 4</xref>. Finite-sample results for estimating the quantile regression parameters under model (8) with Frank copula.</p><p><img src="3-1240171\8f856785-f7c5-4ee7-9b34-ed9aec4cec1d.jpg" /></p><p>The results are based on 400 simulation runs each with a sample size 100.</p><p>point estimator, <img src="3-1240171\e5b3ab40-a378-4bba-9ba2-2883cc4031b9.jpg" />, (Bias);</p><p>the empirical standard deviation,</p><p><img src="3-1240171\638b43b0-845d-465f-91e9-a745f2584c94.jpg" />where<img src="3-1240171\39e47732-5fea-4879-b86c-2c71c8e84df3.jpg" />, (EmpSd); the mean squared error, Bias<sup>2</sup> + EmpSd<sup>2</sup>, (MSE); and the coverage probability of the 95% confidence intervals,</p><p><img src="3-1240171\15f42836-0cfc-472a-9be3-23002f042dfe.jpg" />where <img src="3-1240171\dd3e9ceb-314f-4617-9d80-7971f3ae24ab.jpg" /> is the estimated standard deviation of <img src="3-1240171\44c48f7b-2ad9-4cd6-958d-2481f559a982.jpg" /> by the bootstrap approach, (CP). From the results, we can see that our proposed estimator has much smaller bias and smaller mean squared error than the naive estimator. The confidence intervals coverage probabilities are close to the nominal level 95% in most cases while the naive estimator has the coverage rate far below the nominal level in many cases. Although the proposed estimator of <img src="3-1240171\580e1fa1-5b78-4f1b-a6f3-f34a11a7e12b.jpg" /> has the coverage rate lower than 90% in the first case with Kendall’s tau τ = 0.7 but it still performs better than the naive estimator. As the sample size increases to n = 200 for that case (data omitted here), the coverage probabilities for proposed estimator become close to the nominal level while the coverage probabilities for the naive estimator get worse. This confirms that our estimator is asymptotically correct while the naive estimator is not.</p><p>Then we examine the proposed model diagnostic method when the true model is generated from</p><p><img src="3-1240171\e5dab148-bf21-42d7-94e1-3496e314f445.jpg" /></p><p>where<img src="3-1240171\af96d490-6240-4d39-967a-aeddef0a5251.jpg" />, <img src="3-1240171\1dbf5069-fe65-42b6-927e-15f04cda3604.jpg" />, and</p><p><img src="3-1240171\4aa5b3e9-429c-402f-acc5-2f8aa7f037f8.jpg" />so that <img src="3-1240171\69f212e2-a854-4238-b169-63fc656fc2de.jpg" /> and <img src="3-1240171\283e382d-db03-4452-a63b-261b7773a7b8.jpg" /></p><p>follow Clayton copula with<img src="3-1240171\6dcc04c8-9957-41f5-bd93-0cf59632b23a.jpg" />. We consider &#160;τ = 0.3, 0.5, 0.7 and γ = 0.1, 0.3, 0.5 under n = 100 based on 200 replications.</p><p>Three forms of transformation are fitted: 1) <img src="3-1240171\2fa1739f-f1e3-4ea7-8c20-68ba8fc290ae.jpg" />; 2)<img src="3-1240171\c91749f8-0cec-44ad-9eec-b303f6e0f1a9.jpg" />; 3)<img src="3-1240171\79c810c7-f1a5-4636-87a4-011766053010.jpg" />. <xref ref-type="table" rid="table5">Table 5</xref></p><p>presents the rejection probability<img src="3-1240171\27a79d4e-c8bb-422c-85d6-14449199b370.jpg" />where α = 0.05, and the probability that the fitted model is selected as the one which gives the smallest value of <img src="3-1240171\3f56e77b-4f63-417c-a3ac-a10d7ac281ea.jpg" /> among the three candidates. From the results, we see that when<img src="3-1240171\e8b65421-8530-471c-b3b6-231ec142a597.jpg" />, the rejection probability (type-I error rate) is close to the specified level of α = 0.05. When the fitted model is wrong, the rejection probability (power of the test) is very high in most cases.</p><p><xref ref-type="table" rid="table5">Table 5</xref>. Finite-sample results for the proposed model checking method.</p><p><img src="3-1240171\3318a35d-e444-4c05-92fc-870b793c3af6.jpg" /></p><p>Note: The sample size is 100 and replications are 200. “Power” =<img src="3-1240171\3d145f5a-2926-4984-832d-f9bd9e7711ce.jpg" />, where<img src="3-1240171\af00d4f8-fded-4c25-8ca4-34b3b287bcda.jpg" />. “Selection rate” is the proportion that the fitted model is selected as the one giving the smallest value of <img src="3-1240171\a3fc1b1b-398c-481a-8419-7fe2a762ebdd.jpg" /> among the three candidates.</p><p>Even for the case where the power is relatively low around 40% (the γ = 0.1 quantile for<img src="3-1240171\5d7ac7a1-cfe5-4676-9d7f-ed5362f10c84.jpg" />), the probabilities of selecting the correct model are still high.</p></sec><sec id="s5"><title>5. Data Analysis</title><p>We apply the proposed methodology to analyze the bone marrow transplant data based on 137 leukemia patients provided by [<xref ref-type="bibr" rid="scirp.27915-ref1">1</xref>]. Patients were classified into three risk categories: ALL, AML low-risk, and AML high-risk based on their status at the time of transplantation. The covariates (Z<sub>1</sub>, Z<sub>2</sub>) are coded as ALL (Z<sub>1</sub> = 1, Z<sub>2</sub> = 0), AML low-risk (Z<sub>1</sub> = 1, Z<sub>2</sub> = 0), and AML high-risk (Z<sub>1</sub> = 0, Z<sub>2</sub> = 1). We want to investigate how the risk classification is related to the quantile of the relapse time. Specifically the fitted model is given by</p><disp-formula id="scirp.27915-formula74079"><label>(9)</label><graphic position="anchor" xlink:href="3-1240171\24c06240-4554-4046-b734-7b043d3225b3.jpg"  xlink:type="simple"/></disp-formula><p>The results are summarized in the Tables 6 and 7 based on B = 1000 bootstrap replications. <xref ref-type="table" rid="table6">Table 6</xref> contains the estimators and model checking tests with <img src="3-1240171\c486c007-c0a9-4ca8-8acf-9ea2f403fd98.jpg" />. The p-value is the testing result by the model checking approach provided in SubSection 3.3. Since all the p-values are greater than 0.05, we adopt the model in (9) for further analysis.</p><p>From the analysis we see that patients of AML lowrisk had longer relapse time than those in the other two groups and the difference is more obvious for those with earlier relapse. For example, the 10% quantile of the relapse time in the AML low-risk group is 3.2964 times of that in ALL group and 4.751 times of that in AML highrisk group. The group differences are statistically significant for the 10% and 30% quantiles. but no longer significant for the 50% quantile.</p></sec><sec id="s6"><title>6. Concluding Remarks</title><p>In this paper, we consider quantile regression analysis for analyzing the failure-time of a non-terminal event under the semi-competing risks setting. The Archimedean copula assumption is adopted to specify the dependency between the two correlated events. This assumption is utilized to calculate the weight for bias correction in the estimation of quantile regression parameters. Here we focus on the case of discrete covariates and derive the asymptotic properties of the proposed estimators. The bootstrap method is suggested for variance estimation. For checking the adequacy of the fitted model, a model diagnostic approach is proposed. Simulation results confirm that the proposed methods have good performances in finite samples. In the data analysis, we see that the risk classification is particularly influential for earlier relapse. The methodology can be extended to allow for continuous covariates by employing some smoothing techniques but the corresponding theoretical analysis is beyond the scope of the paper.</p><p><xref ref-type="table" rid="table6">Table 6</xref>. Estimation of quantile regression parameters and model checking test based on the bone marrow transplant data.</p><p><img src="3-1240171\345d6cba-c740-49f4-8f1e-22654030428d.jpg" /></p><p><xref ref-type="table" rid="table7">Table 7</xref>. Comparison of leukemia relapse time for the three risk groups.</p><p><img src="3-1240171\c980daef-a699-494f-9a54-b3453a4b383d.jpg" /></p></sec><sec id="s7"><title>7. Acknowledgement</title><p>This paper was financially supported by the National Science Council of Taiwan (NSC100-2118-M-194-003- MY2).</p></sec><sec id="s8"><title>REFERENCES</title></sec><sec id="s9"><title>Appendix: Proofs of Theorem 1</title><p>The proof follow the outline similar to the proof in [<xref ref-type="bibr" rid="scirp.27915-ref13">13</xref>]. The technical details need to be adjusted for dependent censoring which make things harder.</p><p>Define</p><p><img src="3-1240171\e8b28d37-3b85-4cb5-81ed-3dee44f9a9a3.jpg" /></p><p><img src="3-1240171\f2e10f41-53e2-481d-bdb9-e174ffa398f7.jpg" /></p><p><img src="3-1240171\e0037b7f-5d0e-4105-af49-99ce5f7c520c.jpg" /></p><p><img src="3-1240171\86e975a8-75c7-492f-8e52-d6f7469d108e.jpg" /></p><p>For simplicity, we use <img src="3-1240171\e1788423-6b09-4560-a78c-695912fb54a9.jpg" /> and <img src="3-1240171\337144e9-b4c0-4ef8-a87f-2d94fd948608.jpg" /> to denote supremum taken over<img src="3-1240171\b98ea981-caf4-490a-a6e1-cd882b7518b8.jpg" />, <img src="3-1240171\b8cae83d-f59f-46bb-9fd3-fa4547f1f50d.jpg" />and <img src="3-1240171\b719f28c-9433-4ad4-aa1d-e12dea8050da.jpg" /> respectively.</p><p>First, we show that <img src="3-1240171\e2c5aa6d-62b3-4a6b-9928-b08ea9176841.jpg" /> converges uniformly to</p><p><img src="3-1240171\71d431d5-658f-41b4-883e-2a2f3b740f6a.jpg" />. Since <img src="3-1240171\a7267f79-0d8f-4394-b605-cdf3df41651c.jpg" /> is finite, <img src="3-1240171\0f1747c5-a209-4ed2-8130-036221b72274.jpg" />as</p><p><img src="3-1240171\3266f04d-5022-490c-9276-533e8595801c.jpg" />. Hence by [<xref ref-type="bibr" rid="scirp.27915-ref17">17</xref>], <img src="3-1240171\30ffa062-76aa-4ea8-835f-673507e684c8.jpg" />is consistent for <img src="3-1240171\4fc34cd5-0355-4cf6-87ca-8cb33b31ccd9.jpg" /> for all<img src="3-1240171\c6e0e286-3b2a-40bc-81a2-623e15a89e8e.jpg" />. Using this and conditions C2, it implies that <img src="3-1240171\644ea0a0-5dce-4392-ac89-0783ec59bd69.jpg" /> with probability 1 for large enough n. From condition C3, <img src="3-1240171\180a9e43-61ad-4e85-8428-2deca448def0.jpg" />and <img src="3-1240171\e828798b-2f90-41b3-a05e-ea68c8c3ba2f.jpg" /> converge to</p><p><img src="3-1240171\879ec501-345b-42f2-9e29-1683ded17fd4.jpg" />and <img src="3-1240171\a31f52d6-d939-4a5a-a8ba-ae5f77f40dc2.jpg" /> uniformly for<img src="3-1240171\1264623c-5d98-43b9-9316-4055933afa89.jpg" />. Condition C4 (iii) together with conditions C1 and C3 ensure the uniform boundedness of the first two derivatives of <img src="3-1240171\42240e8d-ce3c-40ef-9826-7803774bcf2a.jpg" /> and <img src="3-1240171\3e6b865b-b2f8-4b30-aa89-b4ad7ba629f6.jpg" /> for <img src="3-1240171\a0a673b0-2467-4e7f-be6b-fe348567b541.jpg" /> and</p><p><img src="3-1240171\3ae55f72-c289-4f12-b010-45b8b57048fb.jpg" />, same as the regularity condition in [<xref ref-type="bibr" rid="scirp.27915-ref19">19</xref>]. Hence as<img src="3-1240171\c688976e-b71b-4eda-a091-6e3ef1d1c016.jpg" />, by [<xref ref-type="bibr" rid="scirp.27915-ref17">17</xref>] and [<xref ref-type="bibr" rid="scirp.27915-ref19">19</xref>], <img src="3-1240171\ee573da5-626e-431f-82e8-b9ca2c5692fc.jpg" />also converges to <img src="3-1240171\ec74809d-e058-4e67-9903-c29726767199.jpg" /> uniformly for<img src="3-1240171\05cad3d7-4ced-4fb9-b832-85e53fe62b91.jpg" />. Then there exists a number <img src="3-1240171\189af3e2-cd6a-4f18-ab86-7c089f7e79ad.jpg" /> such that <img src="3-1240171\a8a24370-f909-4c43-9852-e5a73b8ab3c3.jpg" /> and <img src="3-1240171\0881750a-f994-4e04-b8d6-3977a770513d.jpg" /> fall into <img src="3-1240171\1e6ebe40-eeaa-4843-a313-49b16bfb1c91.jpg" /> with probability 1 for large enough n and all <img src="3-1240171\16c1224f-0f49-4d63-bf26-7d5c9e7e614b.jpg" /> by condition C3 and the uniform convergence of the two estimators. Denote<img src="3-1240171\c9f756e1-7d31-48b8-9b9d-f1a9639a41d7.jpg" />. Condition C4 (iii)</p><p>implies that<img src="3-1240171\4c243fbd-b87c-43db-87c2-7e7e445c061c.jpg" />, <img src="3-1240171\30d0203d-3ad5-4900-93d3-54461f3ed981.jpg" />and</p><p><img src="3-1240171\5a83756f-ddee-43fd-b78b-6aca787ea8e2.jpg" />are all uniformly bounded above for <img src="3-1240171\2b96587f-cfef-4cc9-bc34-ff34e9ae490d.jpg" /> and<img src="3-1240171\af2c6769-5930-41d2-a616-b9043e3d7972.jpg" />. Hence</p><p><img src="3-1240171\daa5304f-c3c4-4d77-a060-3e240b7fb500.jpg" />converges to <img src="3-1240171\6efc6f4a-650e-4aa4-b31d-d2a096b57975.jpg" /></p><p>uniformly for <img src="3-1240171\d0edc7e5-1785-435e-8cd5-64a949ca11d8.jpg" /> and<img src="3-1240171\9fa7febe-448f-4fe1-9eab-72aee83200d4.jpg" />. This result and the uniform convergence of <img src="3-1240171\68bff31d-80f8-4e4d-83c3-e07da30cd6f9.jpg" /> imply the uniform convergence of <img src="3-1240171\eab4954f-8c5d-4e89-9a5d-dfac05153fe1.jpg" /> for <img src="3-1240171\f524433a-124d-48c8-8360-9e7e3ced3173.jpg" /> and<img src="3-1240171\b04fe768-023d-4977-a670-ea0495e95f0f.jpg" />. Hence we have <img src="3-1240171\f4e71466-827f-43be-9015-7059aa709c8f.jpg" /></p><p>The function class</p><p><img src="3-1240171\dbdf7ae9-3ada-4a2e-a003-2c7e738117ec.jpg" /></p><p>is Donsker because the class of indicator functions is Donsker and both <img src="3-1240171\1d7c8f4a-2789-4e81-9039-5efa5c4a9769.jpg" /> and <img src="3-1240171\937985a3-2c57-4550-b35c-5d76f56fe6af.jpg" /> are uniformly bounded by conditions C1 and C3. Therefore, by Glivenko-Cantelli theorem, <img src="3-1240171\d23d5afd-ab15-493b-aec3-ace895bd3e64.jpg" />. Also</p><disp-formula id="scirp.27915-formula74080"><label>(1)</label><graphic position="anchor" xlink:href="3-1240171\6bdf6efb-6050-47ca-ba9a-b51429be04a4.jpg"  xlink:type="simple"/></disp-formula><p>Then the consistency of <img src="3-1240171\ea4a53a8-3e26-4666-be81-9cf40b28e278.jpg" /> comes from the identifiability condition C5 using the arguments in the proof of Theorem 1 in [<xref ref-type="bibr" rid="scirp.27915-ref13">13</xref>].</p><p>Similar to [<xref ref-type="bibr" rid="scirp.27915-ref13">13</xref>] the following lemma holds with the uniform boundedness of Z, <img src="3-1240171\b21b3275-7836-4933-810b-2912c352088c.jpg" />and <img src="3-1240171\b8a9dc99-ec40-4790-b0c0-9409b7f002a5.jpg" /> that comes from conditions C1, C3 (i) and C3 (ii).</p><p>Lemma 1. For any positive sequence <img src="3-1240171\a55be339-b858-4081-8f56-61eac6da21f0.jpg" /> satisfying<img src="3-1240171\ac9dd529-2a1b-45f9-a970-44e0ff389ca1.jpg" />,</p><p><img src="3-1240171\529bcb50-256a-4104-aeea-b0265e2d6417.jpg" /></p><p>Now, we provide the proof for the asymptotic normality of<img src="3-1240171\382c0c03-a925-48d4-b098-302dcf0f777f.jpg" />. One can write</p><p><img src="3-1240171\4100b200-678e-4b6f-93f8-1f92e288bbb1.jpg" /></p><p>From the uniform convergence and asymptotic weak convergence of <img src="3-1240171\85e482f8-ef05-4113-9856-9dd330ef8b5b.jpg" /> and condition C3, we have <img src="3-1240171\047f3ec2-a94d-40c4-8824-8d908af48cfb.jpg" /> for any r &gt; 0. Hence the above quantity is dominated by the first term<img src="3-1240171\fc49356a-2bc6-4312-8a88-a1ad87da7888.jpg" />. By Lemma 1 and the uniform convergence of <img src="3-1240171\f68ba9e2-331a-496c-b626-e2ba9e44f141.jpg" /> to<img src="3-1240171\4720c886-785b-417a-aca9-d9a3f4921380.jpg" />,</p><p><img src="3-1240171\8b36ee12-4de1-461e-83e6-5aa93d751551.jpg" /></p><p>where <img src="3-1240171\12ac7fc5-ec8d-4dfb-8045-6fcde5a29010.jpg" /> denotes asymptotic equivalence uniformly in<img src="3-1240171\81035790-e613-4e74-bac2-8f0ebb26eae7.jpg" />. Applying Taylor expansions for <img src="3-1240171\ced11273-901c-4a2f-9705-57d83ddfd326.jpg" /> at<img src="3-1240171\c49a3407-93f2-4db1-99fd-20a29d26a495.jpg" />, and using the uniform convergence of <img src="3-1240171\a730c2de-deea-4a80-9f16-491bf46ed7af.jpg" /> to<img src="3-1240171\8dcb9360-586d-4d6e-bc4c-355a84fdb340.jpg" />, we have</p><p><img src="3-1240171\e3630325-eeba-4ca5-9a00-da2f28604143.jpg" /></p><p>where<img src="3-1240171\e221cac1-a3b3-4121-acfc-39be099f7b0d.jpg" />. Since<img src="3-1240171\e9b9f890-84ff-4c47-861e-688117961289.jpg" />,</p><disp-formula id="scirp.27915-formula74081"><label>(2)</label><graphic position="anchor" xlink:href="3-1240171\66c3917f-e7ed-45aa-97ca-27f0dcd6e89e.jpg"  xlink:type="simple"/></disp-formula><p>It remains to prove the weak convergence of <img src="3-1240171\0eb68ec0-da9d-4fec-9103-978a2b849374.jpg" /> to a zero-mean Gaussian process. It follows that</p><p><img src="3-1240171\5c7de176-c3a2-44e7-9433-3ab921ebfb57.jpg" /></p><p>The first two terms (I) and (II) can be proved to converge to zero-mean Gaussian processes by applying the arguments in [<xref ref-type="bibr" rid="scirp.27915-ref13">13</xref>] as follows. The family</p><p><img src="3-1240171\3186bc3d-7f79-4446-9141-1d33ffe34586.jpg" /></p><p>is Donsker by the Lipschitz continuity of <img src="3-1240171\0149ce66-ff81-4169-bb46-901e35d2490f.jpg" /> (condition C4 (i)) and uniformly boundedness of <img src="3-1240171\2e2d5abb-b9b6-4f9d-a489-0652ba66f310.jpg" /> and <img src="3-1240171\d03d8bf1-b6d0-4a60-98bb-58757ed6e729.jpg" /> (conditions C1 and C3). Thus, the first term</p><p><img src="3-1240171\febd3753-e1fa-4185-8001-94256b897be4.jpg" /></p><p>converges weakly to a zero-mean Gaussian process.</p><p>Denote <img src="3-1240171\dfb6e230-bb0e-462e-9a9c-16f68115ab0b.jpg" /> and <img src="3-1240171\88ef0dca-0c1b-4dd1-beff-c335b1b7c663.jpg" /> as the at-risk processes at time t. Let</p><p><img src="3-1240171\ff663c40-74ec-45f6-978b-69a9323a8b6c.jpg" />,</p><p><img src="3-1240171\f0b46424-96c7-4b5b-ad94-b8427a14b9da.jpg" />,</p><p><img src="3-1240171\ecd940d7-4f5f-4707-a5a3-5f38c2902ff8.jpg" />.<img src="3-1240171\0828395a-749c-48b1-ba35-40d7c5477da1.jpg" />.</p><p>Then <img src="3-1240171\4f737c5f-0275-4bdc-b08e-691a55809a6f.jpg" /> is a martingale.</p><p>From martingale representation theory for univariate independent censoring,</p><p><img src="3-1240171\c92b2889-d508-4c60-bcbe-3437ef8f851f.jpg" /></p><p>So the second term can be written as</p><p><img src="3-1240171\1e4ab514-47dd-415a-847d-38dc23ce3ffa.jpg" /></p><p>where<img src="3-1240171\46177fc2-9033-4498-9ec8-889e1e8169df.jpg" />.</p><p>From uniform boundedness of<img src="3-1240171\620f7387-b329-4258-853a-e6746dd731f1.jpg" />, <img src="3-1240171\b5360739-871a-4f10-8861-9ecd2f405ca2.jpg" />and<img src="3-1240171\83613f7e-17cd-4b60-93e5-9fb87a7e3aa8.jpg" />, it is easy to show that</p><p><img src="3-1240171\51647910-70a8-4db4-9e3e-7d486be6b802.jpg" />is Lipschitz in b. Then similarly <img src="3-1240171\f437683f-4fd1-41fb-b7d0-73a0d69eff57.jpg" /> can be shown to be Donsker, and the second term also converges weakly to a zero-mean Gaussian process.</p><p>For the third term<img src="3-1240171\f6eef73f-e00e-449a-8cf3-1b31d8fc7ba7.jpg" />, recall</p><p><img src="3-1240171\fd32ff6f-5635-4b7c-8838-62a6055e8af4.jpg" /></p><p>with<img src="3-1240171\2ccd419e-8897-4b4c-834e-fe74a20c71bf.jpg" />. Denote</p><p><img src="3-1240171\08023f34-2856-448b-8be7-80441cf03002.jpg" />,</p><p><img src="3-1240171\48df4e4a-938c-4af2-8fab-5b6308b8afe7.jpg" /></p><p>and</p><p><img src="3-1240171\ffbc8ab6-617e-48bd-aa00-a6d01c6c4aad.jpg" />.</p><p>So for<img src="3-1240171\2bc093d4-4c1c-494c-b805-9a3d5bb54fbb.jpg" />,</p><p><img src="3-1240171\d2d19144-ea84-4ab5-b09d-20836682b37b.jpg" /></p><p>For notation brevity, denote</p><p><img src="3-1240171\b415a5c2-512a-441e-975a-c08aa1fd1902.jpg" />,</p><p><img src="3-1240171\3d6c1ed0-e413-491e-824f-531b9b471ee6.jpg" /></p><p>and</p><p><img src="3-1240171\25202482-64bc-495c-9786-53f4398cb0ff.jpg" />.</p><p>The third term becomes</p><p><img src="3-1240171\a1329d35-ca37-413e-95f0-d0f42de7ed7d.jpg" /></p><p>Since <img src="3-1240171\9e1d97d8-9f2b-49e4-b7d9-15567c2357d3.jpg" /> is finite, <img src="3-1240171\2c671276-1b18-4c9b-b88d-de098041466f.jpg" />by condition C1 for all<img src="3-1240171\64a9594a-29ca-4840-8e2e-6b0723746fb9.jpg" />. So <img src="3-1240171\d0e40bfe-6966-4878-ac15-2839838ffe62.jpg" /> with <img src="3-1240171\86778110-41e1-4d34-85e4-a773577be22e.jpg" /> follows a Gaussian distribution. Let</p><p><img src="3-1240171\0de37314-78da-4759-9d24-919474ef28ab.jpg" /></p><p>Now term <img src="3-1240171\ebe87bd3-4c41-430b-92b4-76a4aa66b76c.jpg" /> is</p><p><img src="3-1240171\d5344ba1-15ed-4358-a883-26404260636e.jpg" /></p><p>which follows a Gaussian distribution by the boundedness of <img src="3-1240171\20d21e95-6c29-438a-b685-7662e6752b1a.jpg" /> and<img src="3-1240171\1086757e-c59e-40b8-aed2-556cf47ac8f6.jpg" />.</p><p>Denote</p><p><img src="3-1240171\12387aab-75f3-4fdd-b21d-c46c8dc049ec.jpg" />,</p><p><img src="3-1240171\44bc618b-6760-419a-a792-6eb39e078480.jpg" />.</p><p>Denote</p><p><img src="3-1240171\7b2852fe-3783-46c5-8606-6099ba401349.jpg" /></p><p>where</p><p><img src="3-1240171\4eca601a-be17-422f-a2c1-4daffa3c32f3.jpg" />.</p><p><img src="3-1240171\94bfb42a-c1ff-4d15-aa3e-5c7c414bed04.jpg" />.</p><p>Then</p><p><img src="3-1240171\87d9aab4-eba7-4469-9dcf-7fc78ccb8454.jpg" /></p><p>is a martingale. Then</p><p><img src="3-1240171\e63766ed-e238-4300-ba7c-de14d4348d39.jpg" /></p><p>Now similar to the martingale expression for the second term<img src="3-1240171\1bf37b66-bdcf-4897-93e5-bf792daf43b8.jpg" />, we have term <img src="3-1240171\5d7e874a-f5c2-4b55-bcc6-8e584787ed60.jpg" /> as</p><p><img src="3-1240171\0a720c73-071f-4991-8a94-b13d23f8d43c.jpg" /></p><p>where</p><p><img src="3-1240171\2a943268-01af-4a33-bb21-b45045923b79.jpg" />.</p><p>Similar as (II) above, <img src="3-1240171\bea77dca-f512-4c6d-a2e3-b23b9403baf6.jpg" />is Lipschitz in b, and <img src="3-1240171\afe14d00-e36b-4d09-9625-07a6e288017d.jpg" /> is Donsker. Thus the term (B) converges weakly to a zero-mean Gaussian process.</p><p>Finally, for term<img src="3-1240171\4bebd4e8-18e1-46c7-b782-524ffbdcdb77.jpg" />, let</p><p><img src="3-1240171\4e969697-ffaf-45a5-8b7b-217978d8d68a.jpg" /></p><p>be the crude hazard function in [<xref ref-type="bibr" rid="scirp.27915-ref17">17</xref>],</p><p><img src="3-1240171\31ed7d6d-a320-4fa0-abff-c765da3ae70f.jpg" />.</p><p><img src="3-1240171\ec9b59ff-253c-4311-8e2a-b67b82e4fe12.jpg" />.</p><p>Then</p><p><img src="3-1240171\f92f0708-f8fa-43ff-a963-d7da3925a4e0.jpg" /></p><p>is a martingale. From [<xref ref-type="bibr" rid="scirp.27915-ref17">17</xref>], we have</p><p><img src="3-1240171\62224c6c-56e0-43e6-b9de-9abeb85f0a81.jpg" /></p><p>where</p><p><img src="3-1240171\0cb662ae-6eae-4b8c-8304-ca059b124bbc.jpg" /></p><p>Similar to terms (A) and (B), we have term (C) equals</p><p><img src="3-1240171\5ecafe8d-9b16-4cad-ac76-50c4485385dd.jpg" /></p><p>where</p><p><img src="3-1240171\8d49fda1-de6a-4dcc-8a48-df5ed5080a8e.jpg" /></p><p><img src="3-1240171\523a984b-8e9e-4f1e-9c91-f876b8b1db25.jpg" /></p><p><img src="3-1240171\5ba0f34d-3751-48fa-a718-e108c2c877c3.jpg" /></p><p>Then each of the three terms in (C) can be shown to converge to zero-mean Gaussian process similarly as above.</p><p>Summarizing the results above, <img src="3-1240171\9ffb88ed-3c7b-4593-ae73-188f32c266f9.jpg" />converges weakly to a zero-mean Gaussian process. 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