{"doi":"10.1016/j.jalz.2018.06.043","title":"P1‐042: SUPPORTING DISEASE MODIFYING THERAPIES VIA ANALYSES OF THE LINK BETWEEN CLINICAL ENDPOINTS AND BIOMARKERS IN ALZHEIMER'S DISEASE CLINICAL TRIALS","abstract":null,"journal":"Alzheimer's & Dementia","year":2018,"id":624194,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1430704,"name":"Ying Tian","orcid":"0000-0002-8596-8891","position":1,"is_corresponding":false},{"id":1613458,"name":"John O'Gorman","orcid":null,"position":2,"is_corresponding":false},{"id":884677,"name":"Tianle Chen","orcid":"0000-0001-6581-8012","position":3,"is_corresponding":false},{"id":1613459,"name":"Philip von Rosenstiel","orcid":null,"position":4,"is_corresponding":false},{"id":1613456,"name":"Xiaopeng Miao","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"P1‐042: SUPPORTING DISEASE MODIFYING THERAPIES VIA ANALYSES OF THE LINK BETWEEN CLINICAL ENDPOINTS AND BIOMARKERS IN ALZHEIMER'S DISEASE CLINICAL TRIALS","abstract":"Current therapies for Alzheimer's disease improve symptoms, but do not have disease modifying effects. Disease modifying therapies are urgently needed to address the considerable burden on patients, caregivers and society. The EMA's 2016 guideline on AD stated that a therapy can be considered disease modifying if the slowing of the rate of decline in clinical signs and symptoms is linked to a significant effect on adequately validated biomarkers that reflect key pathophysiological aspects of the disease. However, it is unclear on how to establish the link between the clinical endpoints and the biomarker data. We propose a set of analyses to explore the link between clinical endpoints and biomarkers: correlation analysis, mediation analysis and meta-analysis. Each analysis evaluates different forms of relationship between the biomarker and clinical endpoint. The correlation analysis quantifies the association between the clinical endpoint and biomarker. The mediation analysis, which appraises the biomarker as an intermediate endpoint, determines to what extent the treatment effect on the clinical endpoint can be attributed to the treatment effect on the biomarker at the individual patient level. The meta-analysis assesses the association between the treatment effect on the biomarker and its effect on the clinical endpoint at the trial/dose level. Using simulations, we examined the roles of these three approaches to assess the link between the clinical endpoints and biomarkers. The simulations demonstrated that a biomarker that is strongly correlated with the clinical endpoint yet may not fully explain the treatment effect on the clinical endpoint. In contrast, a biomarker that mediates all the treatment effect on the clinical endpoint may not necessarily have strong correlation with the clinical endpoint. The mediation analysis approach serves as a capable tool to quantify the treatment effect on the clinical endpoint that can be attributed to the biomarker, even in the absence of strong correlation. Correlation, mediation, and meta analyses are a useful set of tools to explore the link between clinical endpoints and biomarkers as support for disease modifying therapies.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W2896790778","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.14237288,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S1552526018302097?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1552526018302097?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2Fj.jalz.2018.06.043","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1016/j.jalz.2018.06.043","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1016/j.jalz.2018.06.043","host_type":"publisher"},{"url":"https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1016/j.jalz.2018.06.043","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.jalz.2018.06.043","host_type":"journal"}],"fields_of_study":["Health Systems, Economic Evaluations, Quality of Life","Statistical Methods in Clinical Trials"],"mesh_terms":[],"keywords":["Biomarker","Clinical endpoint","Clinical trial","Medicine","Disease","Surrogate endpoint","Endpoint Determination","Biomarker discovery","Meta-analysis","Oncology","Mediation","Internal medicine","Bioinformatics","Proteomics","Biology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T03:01:32.128639Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}