# Failures are hidden

Source: https://onco.cc/bottlenecks/b-negative-results/  
OnCo record `b-negative-results` (Bottleneck). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Negative trials, failed drugs and abandoned programmes are rarely published, so the same mistakes are repeated.

## Summary

A large share of completed clinical trials never report results, and negative trials are published later and less often than positive ones. In the first years after the US results-reporting mandate took effect, only about one in eight applicable trials posted results on ClinicalTrials.gov within the required year, and fewer than half of NIH-funded trials were published within thirty months of completion. Commercial programmes that fail in phase 1 or 2 are usually terminated silently, and preclinical negative results are almost never shared, so companies and academic groups repeat the same experiments and the same mistakes. The costs are duplicated trials, patients exposed to hypotheses already refuted, and meta-analyses biased toward benefit. Enforcement of existing law, journals that publish nulls, and registries of terminated programmes and preclinical negatives would fix most of it.

## Fields

- Kind: Bottleneck
- Last checked: 2026-09-08
- Stage: trials
- Severity: major
- Metrics: Applicable trials reporting results on ClinicalTrials.gov within 12 months of completion, 2008-2013: 13.4% (Anderson et al., NEJM 2015); NIH-funded trials published in a peer-reviewed journal within 30 months of completion: Fewer than half (46%) (Ross et al., BMJ 2012)
- Causes: Journals and careers reward positive, novel findings over nulls.; Sponsors have commercial reasons to keep failed programmes and their data private.; Reporting requirements are weakly enforced; the FDA has issued few penalties under FDAAA 801.; Preclinical work has no registration or reporting infrastructure at all.; Writing up a failure costs time and money that no one funds.

## Sources

- Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015): https://doi.org/10.1056/NEJMsa1409364
- Ross et al., Publication of NIH funded trials registered in ClinicalTrials.gov (BMJ 2012): https://doi.org/10.1136/bmj.d7292
- ClinicalTrials.gov results reporting requirements (FDAAA 801): https://clinicaltrials.gov/policy/reporting-requirements
- AllTrials: https://www.alltrials.net/

## Connected records

- collections: [ClinicalTrials.gov](https://onco.cc/collections/clinicaltrials-gov/), [EU Clinical Trials Register / CTIS](https://onco.cc/collections/eudract-ctis/), [PubMed & Europe PMC](https://onco.cc/collections/pubmed-europepmc/)
- ideas: [A commons of shelved cancer drugs with their full data, open to new hypotheses](https://onco.cc/ideas/idea-tr2-shelved-asset-commons/), [A formal regulatory route for validating a biomarker on archived trial samples](https://onco.cc/ideas/idea-tr2-prospective-retrospective-path/), [A funder-backed, indexed journal of negative and inconclusive cancer results](https://onco.cc/ideas/idea-tr2-negative-results-journal/), [A global ledger of negative results and failed compounds with mandatory deposition](https://onco.cc/ideas/idea-moon-negative-results-ledger/), [A home for the animal and organoid experiments that failed](https://onco.cc/ideas/idea-bio1-negative-preclinical-repository/), [A machine-readable taxonomy of why cancer drugs fail](https://onco.cc/ideas/idea-tr2-failure-taxonomy/), [A public registry of cancer treatments that were later shown not to work](https://onco.cc/ideas/idea-tr2-reversal-registry/), [A public registry of stalled academic assets and shelved company compounds](https://onco.cc/ideas/idea-fund-stalled-asset-registry/), [A public transparency score for every trial sponsor, used by sites and patients](https://onco.cc/ideas/idea-tr2-sponsor-transparency-score/), [A registry for preclinical experiments that did not work](https://onco.cc/ideas/idea-tr2-preclinical-negative-registry/), [A single oncology trial data trust with mandatory deposit within eighteen months](https://onco.cc/ideas/idea-fund-trial-data-trust/), [A standing rulebook for one-patient treatments](https://onco.cc/ideas/idea-bio2-n-of-1-framework/), [A target de-risking index that counts failures as well as successes](https://onco.cc/ideas/idea-tr2-target-failure-index/), [Actually fine sponsors who do not post trial results](https://onco.cc/ideas/idea-tr2-fdaaa-enforcement/), [Alert guidelines and trials when a paper they rely on is retracted](https://onco.cc/ideas/idea-tr2-retraction-propagation/), [An annual map of high-burden questions that nobody is funding](https://onco.cc/ideas/idea-fund-white-space-map/), [Automatically detect when a trial changes its outcomes after the fact](https://onco.cc/ideas/idea-tr2-outcome-switching-monitor/), [Bayesian shrinkage for subgroup claims to stop false 'works in this group' stories](https://onco.cc/ideas/idea-tr1-shrinkage-subgroup-analysis/), [Bounties for documented failed replications of high-impact findings](https://onco.cc/ideas/idea-tr2-replication-bounties/), [Deposit trial results as structured data, not just PDFs](https://onco.cc/ideas/idea-data-structured-trial-results-deposit/), [End the abstract-to-paper gap: require full results with any conference presentation](https://onco.cc/ideas/idea-data-full-data-with-abstract/), [Find peritoneal spread while it is still small, and run complete cytoreduction through networks rather than adding heated chemotherapy](https://onco.cc/ideas/idea-crc-peritoneal-disease-found-early-and-treated-in-networks/), [Funder bonuses for releasing results and data within six months, negatives included](https://onco.cc/ideas/idea-fund-open-results-bonus/), [Give negative trials plenary slots at the big cancer conferences](https://onco.cc/ideas/idea-tr2-negative-plenaries/), [Grant progress reports must list what did not work](https://onco.cc/ideas/idea-tr2-null-result-reporting/), [Listed companies must disclose top-line data, not just 'did not meet endpoint'](https://onco.cc/ideas/idea-tr2-material-failure-disclosure/), [Living systematic reviews of animal and organoid evidence before every new trial](https://onco.cc/ideas/idea-tr2-preclinical-living-reviews/), [Make in vivo metastasis screens a required step in drug discovery](https://onco.cc/ideas/idea-bio2-metastasis-screen-standard/), [Make post-progression sampling a condition of accelerated approval](https://onco.cc/ideas/idea-bio1-approval-linked-progression-sampling/), [Match therapy to the type of scar-forming cell in the tumour](https://onco.cc/ideas/idea-bio2-caf-subtype-assignment/), [No new trial approval until the sponsor has reported its old ones](https://onco.cc/ideas/idea-tr2-irb-results-gate/), [One definitive ketogenic diet trial in glioblastoma, then stop](https://onco.cc/ideas/idea-nl-ketogenic-gbm-definitive-trial/), [Patient-level data from failed trials becomes open by default after two years](https://onco.cc/ideas/idea-tr2-failed-trial-ipd-default/), [Pay investigators for finishing and publishing trials, not for enrolling patients](https://onco.cc/ideas/idea-fund-trial-completion-bonus/), [Plain-language trial results returned to every participant within a year](https://onco.cc/ideas/idea-moon-results-back-to-participants/), [Pre-register animal efficacy studies like clinical trials](https://onco.cc/ideas/idea-bio1-preclinical-preregistration/), [Pre-registration and results reporting for real-world cancer studies](https://onco.cc/ideas/idea-data-observational-study-registration/), [Promote academics for trials completed, data shared and findings replicated](https://onco.cc/ideas/idea-fund-academic-promotion-reform/), [Public post-mortem reports when a cancer drug programme is stopped](https://onco.cc/ideas/idea-tr2-termination-reports/), [Publish every complete response letter and negative opinion across all regulators](https://onco.cc/ideas/idea-reg-publish-all-rejections/), [Record what happens when doctors use cancer drugs off-label](https://onco.cc/ideas/idea-tr2-off-label-outcome-registry/), [Registered reports for cancer biology: the plan is peer-reviewed before the result](https://onco.cc/ideas/idea-tr2-preclinical-registered-reports/), [Report gallbladder cancer as its own population in every biliary trial](https://onco.cc/ideas/idea-gbc-report-gallbladder-separately-in-biliary-trials/), [Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint](https://onco.cc/ideas/idea-pdac-stromal-reprogramming-not-depletion/), [Require a randomised phase 2 before any phase 3](https://onco.cc/ideas/idea-tr1-randomised-phase-2-before-phase-3/), [Require every oncology candidate to publish how much reaches the brain](https://onco.cc/ideas/idea-bio2-brain-exposure-disclosure/), [Rescue the biological samples from failed trials for biomarker research](https://onco.cc/ideas/idea-tr2-failed-trial-biobank/), [Robot-placed catheters and live imaging for drug infusion into brain tumours](https://onco.cc/ideas/idea-bio2-robotic-convection-delivery/), [Score every preclinical model by how often it predicted the clinical result](https://onco.cc/ideas/idea-tr2-model-report-cards/), [Small grants that pay scientists to write up abandoned projects](https://onco.cc/ideas/idea-tr2-writeup-grants/), [Soften the tissue that new metastases need in order to grow](https://onco.cc/ideas/idea-bio2-matrix-stiffness-prevention/), [Stop failing trials earlier with pre-registered aggressive futility rules](https://onco.cc/ideas/idea-tr1-aggressive-futility-boundaries/), [Use pre-surgery immunotherapy windows as the field's biomarker engine](https://onco.cc/ideas/idea-bio2-neoadjuvant-biomarker-engine/)
- drugs: [Bempegaldesleukin](https://onco.cc/drugs/bempegaldesleukin/), [Epacadostat](https://onco.cc/drugs/epacadostat/), [Eprenetapopt](https://onco.cc/drugs/eprenetapopt/), [Iniparib](https://onco.cc/drugs/iniparib/), [Magrolimab](https://onco.cc/drugs/magrolimab/), [Melphalan flufenamide](https://onco.cc/drugs/melflufen/), [Rovalpituzumab tesirine](https://onco.cc/drugs/rovalpituzumab-tesirine/), [Tiragolumab](https://onco.cc/drugs/tiragolumab/), [Trastuzumab duocarmazine](https://onco.cc/drugs/trastuzumab-duocarmazine/), [Tusamitamab ravtansine](https://onco.cc/drugs/tusamitamab-ravtansine/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [FDA Oncology Center of Excellence](https://onco.cc/institutions/fda-oce/), [National Cancer Institute (NIH)](https://onco.cc/institutions/nci/), [Vivli](https://onco.cc/institutions/vivli/), [Yale University Open Data Access (YODA) Project](https://onco.cc/institutions/yoda-project/)
- key papers: [Capivasertib plus paclitaxel as first-line treatment for metastatic triple-negative breast cancer: results from the randomised, global phase III CAPItello-290 trial](https://onco.cc/key-papers/paper-capitello-290-capivasertib-paclitaxel-ann-oncol-2026/), [Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials](https://onco.cc/key-papers/paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995/), [Compliance with results reporting at ClinicalTrials.gov](https://onco.cc/key-papers/paper-anderson-n-engl-j-med/), [Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7)](https://onco.cc/key-papers/paper-quenet-prodige-7-hipec-peritoneal-colorectal-lancet-oncol-2021/), [Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival](https://onco.cc/key-papers/paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014/), [Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma: clinical outcomes of the phase III intergroup trial Alliance/CALGB 50303](https://onco.cc/key-papers/paper-calgb-50303-da-epoch-r-vs-r-chop-jco-2019/), [Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in KRAS wild-type advanced or metastatic colorectal cancer (CALGB/SWOG 80405)](https://onco.cc/key-papers/paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017/), [Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease](https://onco.cc/key-papers/paper-caret-beta-carotene-retinol-lung-cancer-nejm-1996/), [GETUG-AFU 15: androgen deprivation alone or with docetaxel in non-castrate metastatic prostate cancer](https://onco.cc/key-papers/paper-gravis-getug-afu-15-docetaxel-lancet-oncol-2013/), [KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery](https://onco.cc/key-papers/paper-keynote-564-nejm-2021/), [Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-goya-obinutuzumab-vs-rituximab-chop-dlbcl-jco-2017/), [Positron emission tomography-guided treatment in early-stage favorable Hodgkin lymphoma: final results of the international, randomized phase III HD16 trial by the German Hodgkin Study Group](https://onco.cc/key-papers/paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019/), [Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis](https://onco.cc/key-papers/paper-ross-bmj/), [Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX)](https://onco.cc/key-papers/paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019/), [Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma](https://onco.cc/key-papers/paper-halo-301-pegvorhyaluronidase-jco-2020/), [Reproducibility Project: Cancer Biology found that landmark preclinical results mostly shrank or vanished on replication](https://onco.cc/key-papers/paper-reproducibility-project-cancer-biology-elife-2021/), [Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial](https://onco.cc/key-papers/paper-plco-chest-radiograph-lung-cancer-mortality-jama-2011/), [Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma](https://onco.cc/key-papers/paper-belinda-tisagenlecleucel-second-line-nejm-2022/), [STOpCaP: docetaxel or bisphosphonates added to standard of care in hormone-sensitive prostate cancer, a systematic review and meta-analysis](https://onco.cc/key-papers/paper-vale-stopcap-docetaxel-bisphosphonates-lancet-oncol-2016/), [Stupp 2005: temozolomide added to radiotherapy for newly diagnosed glioblastoma](https://onco.cc/key-papers/paper-stupp-temozolomide-nejm-2005/), [TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival](https://onco.cc/key-papers/paper-tropion-breast01-jco-2024/)
- cancers: [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- roadmaps: [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/), [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/), [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/), [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- trials: [Alliance/CALGB 50303](https://onco.cc/trials/calgb-50303/), [ASPREE (ASPirin in Reducing Events in the Elderly)](https://onco.cc/trials/aspree/), [BWEL (Breast Cancer Weight Loss, Alliance A011401)](https://onco.cc/trials/bwel/), [ERGO2: ketogenic diet and fasting during re-irradiation of recurrent glioma](https://onco.cc/trials/ergo2/), [EURAMOS-1](https://onco.cc/trials/euramos-1/), [GHSG HD16](https://onco.cc/trials/hd16/), [GOYA](https://onco.cc/trials/goya/), [VITAL (VITamin D and OmegA-3 TriaL)](https://onco.cc/trials/vital/), [WHEL (Women's Healthy Eating and Living)](https://onco.cc/trials/whel/)
- technologies: [Antineoplastons (Burzynski clinic)](https://onco.cc/technologies/antineoplastons/), [Dietitian-led weight-loss programmes in HR-positive breast cancer](https://onco.cc/technologies/dietitian-led-weight-loss-breast/), [Hydrazine sulfate](https://onco.cc/technologies/hydrazine-sulfate/), [Ketogenic diets in glioblastoma](https://onco.cc/technologies/ketogenic-diet-glioblastoma/), [Mistletoe extracts (Iscador, Helixor)](https://onco.cc/technologies/mistletoe-extracts/), [Shark cartilage (AE-941, Neovastat)](https://onco.cc/technologies/shark-cartilage/), [The questionnaires that were never returned, and the people never asked](https://onco.cc/technologies/rejuv-measure-missing-data-and-who-is-not-asked/), [Vitamin D and omega-3 supplementation](https://onco.cc/technologies/vitamin-d-omega3-supplementation/), [What a difference has to be before a person would notice it](https://onco.cc/technologies/rejuv-measure-minimally-important-difference/)
- terms: [Declaration of Helsinki](https://onco.cc/terms/declaration-of-helsinki/)

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