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Failure-mode index

Search what already failed

A searchable index of real negative results, null findings, and replication failures from the published literature — so you can learn what didn't work before repeating it.

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record (title, authors, DOI) compiled from open scholarly databases, with the abstract shown in full only where the paper is openly licensed (e.g. Creative Commons); otherwise a short excerpt is shown for reference under fair use. WASTE classifies each work by failure type; classifications are automated and approximate.

422 results in Replication Failure · page 4 of 15

Replication FailureMedicine

IVUS-Guided versus Angiography-Guided PCI in Unprotected Left Main Coronary Disease

Luca Testa, J M De La Torre Hernandez, Giovanni Luigi De Maria et al. · 2026 · New England Journal of Medicine

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used for revascularization of unprotected left main coronary artery disease. Whether intravascular ultrasonographic (IVUS) guidance during PCI results in better clinical…

View details →DOI: 10.1056/nejmoa2600440Cited by 16
Replication FailureOpen accessMedicine

Rectal diclofenac versus indomethacin for prevention of post-ERCP pancreatitis (DIPPP): a multicentre, double-blind, randomised, controlled trial

Xiaoyu Kang, Mingxing Xia, Jun Wang et al. · 2025 · Gut

BACKGROUND: Recent meta-analyses suggested diclofenac may be superior to indomethacin in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The aim of our study was to compare the efficacy of 100 mg…

View details →DOI: 10.1136/gutjnl-2024-334466Cited by 14
Replication FailureOpen accessMedicine

Inhibition of FcRn with rozanolixizumab in adults with immune thrombocytopenia: Two randomised, double‐blind, placebo‐controlled phase 3 studies and their open‐label extension

Nichola Cooper, James B. Bussel, Maciej Kaźmierczak et al. · 2024 · British Journal of Haematology

Summary Primary immune thrombocytopenia (ITP) is an antiplatelet‐antibody‐mediated disorder with accelerated platelet clearance and decreased platelet production. Rozanolixizumab, a monoclonal IgG4 anti‐FcRn antibody, blocks IgG recycling and decreases IgG levels. We report efficacy and safety of rozanolixizumab in adults with persistent/chronic ITP in 24‐week phase 3 studies (TP0003; TP0006), and their 52‐week open‐label extension (OLE). Primary end‐point was durable clinically meaningful platelet response (DCMPR) of ≥50 × 10 9 /L for 8/12 weeks during Weeks 13–25 in the double‐blind studies.

View details →DOI: 10.1111/bjh.19858Cited by 13
Replication FailureOpen accessMedicine

Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab versus Transarterial Chemoembolization Alone in Intermediate‐stage Hepatocellular Carcinoma: A Multicenter Retrospective Study

Yitao Zheng, Yan‐Jun Xiang, Hongqi Shi et al. · 2024 · Journal of Hepatocellular Carcinoma

Purpose: Combining transarterial chemoembolization (TACE) with systemic therapy has shown significant efficacy for intermediate-stage hepatocellular carcinoma (HCC) patients. This study aimed to validate the therapeutic efficacy of TACE…

View details →DOI: 10.2147/jhc.s461630Cited by 13
Replication FailureOpen accessMedicine

Long-Term Outcomes of Left Bundle-Branch Pacing vs Biventricular Pacing in Heart Failure

Xueying Chen, Xi Liu, Ruogu Li et al. · 2026 · JAMA Cardiology

Importance: Left bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking. Objective: To evaluate the long-term clinical outcomes of LBBP and BiVP. Design, Setting, and Participants: This multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place

View details →DOI: 10.1001/jamacardio.2026.0083Cited by 12
Replication FailureOpen accessMedicine

Ticagrelor vs Prasugrel in Patients With Diabetes and Multivessel Coronary Artery Disease

S Bangalore, Santosh Kumar Sinha, Rakendra Singh et al. · 2026 · JAMA Cardiology

Importance: The optimal dual antiplatelet therapy after percutaneous coronary intervention (PCI) in patients with diabetes is not clearly defined. Although both ticagrelor and prasugrel are potent inhibitors of P2Y purinergic receptor 12…

View details →DOI: 10.1001/jamacardio.2025.5057Cited by 11
Replication FailureOpen accessChemistry

Herbify: an ensemble deep learning framework integrating convolutional neural networks and vision transformers for precise herb identification

Farhan Sheth, Ishika Chatter, Manvendra Jasra et al. · 2025 · Plant Methods

Herbs have historically been central to medicinal practices, representing one of the earliest forms of therapeutic intervention. While synthetic drugs are often highly effective in treating acute conditions, their use is frequently…

View details →DOI: 10.1186/s13007-025-01421-5Cited by 11
Replication FailureOpen accessNeuroscience

Pridopidine in early-stage manifest Huntington’s disease: a phase 3 trial

Ralf Reilmann, Andrew Feigin, Anne Rosser et al. · 2025 · Nature Medicine

Huntington's disease (HD) is a rare, neurodegenerative disorder for which only symptomatic treatments are available. The PROOF-HD study was a randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of pridopidine, a selective Sigma-1 receptor agonist, in HD. The primary and key secondary endpoints, change in total functional capacity (TFC) and composite Unified Huntington's Disease Rating Scale (cUHDRS) score at week 65, were not met in the overall population. The TFC least-squares mean difference between pridopidine and placebo was -0.18 (95% confidence i

View details →DOI: 10.1038/s41591-025-03920-3Cited by 11
Replication FailureOpen accessMedicine

A Smartphone App Self-Management Program for Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial of Clinical Outcomes

Lisa H. Glynn, E Moloney, Stephen Lane et al. · 2025 · JMIR mhealth and uhealth

BACKGROUND: Chronic obstructive pulmonary disease (COPD) negatively impacts clinical health outcomes, resulting in frequent exacerbations, increased hospitalizations, reduced physical activity, deteriorated quality of life, and diminished self-efficacy. Previous studies demonstrated that a self-management program tailored for adults with COPD improves self-management decisions, resulting in a positive effect on clinical health outcomes. Limitations of these studies include issues regarding heterogeneity among interventions used, patient population characteristics, outcome measures, and longitu

View details →DOI: 10.2196/56318Cited by 11
Replication FailureOpen accessChemistry

Synthesis of enantioenriched atropisomers by biocatalytic deracemization

Casey B. Roos, S. Luke Schulert, Lara E. Zetzsche et al. · 2025 · Nature

The synthesis of enantiopure materials is vital for pharmaceutical and agrochemical industries owing to the inherently chiral nature of biological systems and the fact that two enantiomers can have markedly different biochemical…

View details →DOI: 10.1038/s41586-025-09738-wCited by 10
Replication FailureOpen accessPsychology

Concurrent Treatment of Posttraumatic Stress Disorder and Alcohol Use Disorder in Women

Anna Persson, Åsa Axén, Andrea Johansson Capusan et al. · 2025 · JAMA Network Open

Importance: Trauma-focused treatments are effective for posttraumatic stress disorder (PTSD) but are rarely offered to patients with comorbid substance use disorder. Research suggests gender-based differences in prevalence and treatment needs for these patients, but treatment trials have mainly included men. Objective: To evaluate whether integrated trauma-focused psychological treatment (ie, integrated treatment) leads to greater reduction in PTSD symptom severity and weekly alcohol use than usual treatment (ie, relapse prevention) for alcohol use disorder (AUD) in women. Design, Setting, and

View details →DOI: 10.1001/jamanetworkopen.2025.21087Cited by 10
Replication FailureOpen accessPsychology

Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression

Lea J. Mertens, Michael Koslowski, Felix Betzler et al. · 2026 · JAMA Psychiatry

Importance: Psilocybin shows promise in treating depression, although limitations of previous research warrant further research. Objective: To investigate the efficacy and safety of oral psilocybin, 25 mg, with adjunct psychotherapy in…

View details →DOI: 10.1001/jamapsychiatry.2026.0132Cited by 10
Replication FailureOpen accessImmunology and Microbiology

Efficacy of the meningococcal vaccine against Neisseria gonorrhoeae: a randomised clinical trial (MenGO)

Caroline Thng, Sharareh Eskandari, Fengyi Jin et al. · 2026 · npj Vaccines

Neisseria gonorrhoeae (NG) causes significant morbidity globally, and no licensed vaccine currently exists. Observational studies suggest the four-component meningococcal B (4CMenB) vaccine may provide cross-protection against NG. We conducted MenGO, an open-label, randomized controlled trial to evaluate the efficacy, safety, and immunogenicity of 4CMenB against NG in gay and bisexual men (GBM). Participants were randomized 1:1 to receive two doses of 4CMenB, or no vaccine, and were followed for 2 years with 3-monthly visits. 4CMenB vaccination did not significantly reduce gonorrhoea incidence

View details →DOI: 10.1038/s41541-026-01422-yCited by 10
Replication FailureOpen accessMedicine

Randomized Sham-controlled Trial of Targeted Lung Denervation in Patients with Chronic Obstructive Pulmonary Disease (AIRFLOW-3)

Pallav L. Shah, Dirk‐Jan Slebos, Richard Sue et al. · 2025 · American Journal of Respiratory and Critical Care Medicine

Abstract Rationale AIRFLOW-3 was a 1:1 randomized, double-blind, sham-controlled trial of the D’Nerva targeted lung denervation (TLD) system in patients with chronic obstructive pulmonary disease (COPD). Objective To evaluate the impact of…

View details →DOI: 10.1164/rccm.202502-0404ocCited by 10
Replication FailureOpen accessMedicine

Genome-wide association study of idiopathic pulmonary fibrosis susceptibility using clinically curated European ancestry datasets

Daniel Chin, Tamara Hernández-Beeftink, Lauren J. Donoghue et al. · 2026 · European Respiratory Journal

ABSTRACT Background Idiopathic pulmonary fibrosis (IPF) is a rare, incurable lung disease with a median survival of 3-5 years after diagnosis. Treatment options are limited. Genetic association studies can identify new genes involved in disease that might represent potential new drug targets, and it has been shown that drug targets with support from genetic studies are more likely to be successful in clinical development. Previous genome-wide association studies (GWAS) of IPF susceptibility have identified more than 20 signals implicating genes involved in multiple mechanisms, including telome

View details →DOI: 10.1183/13993003.00506-2026Cited by 10
Replication FailureOpen accessMedicine

A Ketogenic Diet for Treatment-Resistant Depression

Min Gao, Megan Kirk, Heather Knight et al. · 2026 · JAMA Psychiatry

Importance: Preclinical evidence and case reports suggest potential therapeutic benefits of ketogenic diets (KDs) in the treatment of depression, but evidence from well-controlled randomized clinical trials (RCTs) is lacking. Objective: To assess the efficacy of a KD compared with a control diet in adults with treatment-resistant depression (TRD). Design, Setting, and Participants: This RCT was conducted between February 22 and June 15, 2024. Participants aged 18 to 65 years with TRD and a score of 15 or greater on the 9-item Patient Health Questionnaire (PHQ-9) from across the UK were include

View details →DOI: 10.1001/jamapsychiatry.2025.4431Cited by 10
Replication FailureOpen accessMedicine

Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression

Julien Vionnet, Jorge P. Torres-Yaguana, Rosa Miquel et al. · 2024 · American Journal of Transplantation

The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver

View details →DOI: 10.1016/j.ajt.2024.12.002Cited by 10
Replication FailureOpen accessMedicine

Transarterial chemoembolization plus atezolizumab and bevacizumab in patients with intermediate hepatocellular carcinoma: a single-arm, phase 2 trial

Kang Wang, Jinkai Feng, Hongming Yu et al. · 2025 · Signal Transduction and Targeted Therapy

Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC), yet its efficacy as a standalone therapy remains suboptimal. This phase 2 trial (ChiCTR2100049829) evaluated the feasibility and safety of TACE combined with atezolizumab and bevacizumab in patients with intermediate-stage HCC. Participants received TACE followed by atezolizumab and bevacizumab until disease progression, unacceptable toxicity, or death. The primary endpoint was objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1

View details →DOI: 10.1038/s41392-025-02427-0Cited by 10
Replication FailureOpen accessMedicine

Tavapadon as Adjunctive Treatment for Parkinson Disease

Hubert H. Fernandez, S. H. Isaacson, Robert A. Hauser et al. · 2026 · JAMA Neurology

Importance: Development of motor fluctuations is common in people with Parkinson disease (PD) treated with oral levodopa, and currently available dopamine (D) agonists adjunctive to levodopa offer additional motor control but may increase…

View details →DOI: 10.1001/jamaneurol.2026.0577Cited by 10
Replication FailureBiochemistry, Genetics and Molecular Biology

Identification of Statistically Significant Features from Random Forests

Jérôme Paul, Michel Verleysen, Pierre Dupont · 2013

Abstract. Embedded feature selection can be performed by analyzing the variables used in a Random Forest. Such a multivariate selection takes into account the interactions between variables but is not easy to interpret in a statistical…

View details →Cited by 10
Replication FailureOpen accessImmunology and Microbiology

A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma

Tomoki Makino, Hiroshi Miyata, Takushi Yasuda et al. · 2024 · Esophagus

BACKGROUND: S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC). METHODS: This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After

View details →DOI: 10.1007/s10388-024-01072-wCited by 10
Replication FailureOpen accessBiochemistry, Genetics and Molecular Biology

A specific microRNA profile as predictive biomarker for systemic treatment in patients with metastatic colorectal cancer

Dennis Poel, Elske C. Gootjes, Lotte Bakkerus et al. · 2020 · Cancer Medicine

BACKGROUND: Palliative systemic therapy is currently standard of care for patients with extensive metastatic colorectal cancer (mCRC). A biomarker predicting chemotherapy benefit which prevents toxicity from ineffective treatment is urgently needed. Therefore, a previously developed tissue-derived microRNA profile to predict clinical benefit from chemotherapy was evaluated in tissue biopsies and serum from patients with mCRC. METHODS: Samples were prospectively collected from patients (N = 132) who were treated with capecitabine or 5-FU/LV with oxaliplatin ± bevacizumab. Response evaluation wa

View details →DOI: 10.1002/cam4.3371Cited by 10
Replication FailureOpen accessMedicine

CAR T-Cell Targeting of Macrophage Colony-Stimulating Factor Receptor

Daniela Achkova, Richard Beatson, John Maher · 2022 · Cells

Macrophage colony-stimulating factor receptor (M-CSFR) is found in cells of the mononuclear phagocyte lineage and is aberrantly expressed in a range of tumours, in addition to tumour-associated macrophages. Consequently, a variety of cancer therapies directed against M-CSFR are under development. We set out to engineer chimeric antigen receptors (CARs) that employ the natural ligands of this receptor, namely M-CSF or interleukin (IL)-34, to achieve specificity for M-CSFR-expressing target cells. Both M-CSF and IL-34 bind to overlapping regions of M-CSFR, although affinity of IL-34 is significa

View details →DOI: 10.3390/cells11142190Cited by 10
Replication FailureOpen accessMedicine

Overall survival with relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): a phase 3 randomised controlled trial

Domenica Lorusso, Laurence Gladieff, David M O'Malley et al. · 2026 · The Lancet

BACKGROUND: Relacorilant is a selective glucocorticoid receptor antagonist that increases the sensitivity of many cancer cell types to chemotherapy. The efficacy and safety of relacorilant plus nab-paclitaxel were assessed in the phase 3 ROSELLA (GOG-3073, ENGOT-ov72, APGOT-Ov10, and LACOG-0223) trial; the combination showed significant improvement in progression-free survival among patients with platinum-resistant ovarian cancer compared with nab-paclitaxel monotherapy. Results of the final overall survival analysis are reported here. METHODS: intravenously on the aforementioned schedule). Pa

View details →DOI: 10.1016/s0140-6736(26)00462-9Cited by 9
Replication FailureOpen accessMedicine

Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial

Mette Kruse Klausen, Signe Justesen, Julie Niemann Pedersen et al. · 2026 · The Lancet

BACKGROUND: Alcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity. METHODS: In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were ass

View details →DOI: 10.1016/s0140-6736(26)00305-3Cited by 9
Replication FailureOpen accessMedicine

Safety and efficacy of adjunct dexamethasone in adults with herpes simplex virus encephalitis in the UK (DexEnceph): a multicentre, observer-blind, randomised, phase 3, controlled trial

Tom Solomon, Cory Hooper, Ava Easton et al. · 2026 · The Lancet Neurology

BACKGROUND: Herpes simplex virus (HSV) encephalitis is characterised by inflammation and swelling of the brain, resulting in death or severe neurocognitive sequelae. HSV encephalitis is treated with the antiviral aciclovir but still has substantial mortality and morbidity. Adjunct corticosteroids are sometimes used, but whether they improve the outcome is unclear. We aimed to establish the safety and efficacy of adjunct corticosteroids in HSV encephalitis. METHODS: In this multicentre, observer-blind, randomised, phase 3 trial, adults with HSV encephalitis admitted to 53 hospitals in the UK we

View details →DOI: 10.1016/s1474-4422(25)00454-5Cited by 9
Replication FailureOpen accessMedicine

Overall Survival With First-Line vs Second-Line CDK4/6 Inhibitor Use in Advanced Breast Cancer

Noor Wortelboer, Annemiek van Ommen-Nijhof, Inge R. Konings et al. · 2026 · JAMA Oncology

Importance: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy are widely used in hormone receptor (HR)-positive, ERBB2-negative advanced breast cancer (ABC). The SONIA trial evaluates the optimal…

View details →DOI: 10.1001/jamaoncol.2025.6585Cited by 9
Replication FailureOpen accessMedicine

A Phase II Study of Potentiation of Pembrolizumab with Binimetinib and Bevacizumab in Refractory Microsatellite-Stable Colorectal Cancer

Robert W. Lentz, Tyler J. Friedrich, Patrick J. Blatchford et al. · 2024 · Clinical Cancer Research

PURPOSE: In this single-institution phase II investigator-initiated study, we assessed the ability of MAPK and VEGF pathway blockade to overcome resistance to immunotherapy in microsatellite-stable metastatic colorectal cancer (MSS mCRC).…

View details →DOI: 10.1158/1078-0432.ccr-24-0090Cited by 9
Replication FailureMedicine

Prehospital Whole Blood in Traumatic Hemorrhage — A Randomized Controlled Trial

Jason Smith, Rebecca Cardigan, Emily Sanderson et al. · 2026 · New England Journal of Medicine

BACKGROUND: Whole-blood transfusion has recently gained favor in the management of severe hemorrhage; however, data from large clinical trials evaluating its clinical effectiveness and safety are lacking. METHODS: We conducted a pragmatic,…

View details →DOI: 10.1056/nejmoa2516043Cited by 9
Replication FailureOpen accessMedicine

Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes

Nicholas A. Marston, Erin A. Bohula, Ajay Bhatia et al. · 2026 · JAMA

Importance: Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with…

View details →DOI: 10.1001/jama.2026.3277Cited by 9