# Trial design, endpoints and cost

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

## TL;DR

A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.

## Summary

The randomised phase 3 trial remains the evidentiary standard, but the way oncology runs it is slow, expensive and often uninformative. Surrogate endpoints such as progression-free survival and response rate correlate weakly with overall survival for most indications, yet they underpin most approvals; more than half of cancer drugs approved by the EMA in 2009-13 had no evidence of survival or quality-of-life benefit at approval, and most still did not years later. Control arms are frequently obsolete by readout, crossover and post-progression therapy blur survival differences, and duration and dose of therapy are almost never tested. Median clinical development costs run to hundreds of millions of dollars per approved drug, which prices out academic questions. Platform and adaptive designs, ctDNA and MRD endpoints, pragmatic registry-based randomisation and clear value frameworks are the tools for faster, cheaper and more honest trials.

## Fields

- Kind: Bottleneck
- Last checked: 2026-09-08
- Stage: trials
- Severity: critical
- Metrics: Median estimated R&D investment to bring a new drug to market (all areas, 2009-2018), capitalised: Median US$985 million, mean US$1.3 billion; oncology among the highest (Wouters, McKee & Luyten, JAMA 2020); Cancer drug indications approved by the EMA 2009-2013 with no evidence of survival or quality-of-life benefit at approval: 57% (Davis et al., BMJ 2017); Trial-level correlations between surrogate endpoints and overall survival in oncology rated weak vs strong (systematic review): 52% weak, 23% strong (Prasad et al., JAMA Internal Medicine 2015); Median overall survival gain of cancer drugs approved by FDA 2002-2014: 2.1 months (Fojo, Mailankody & Lo, JAMA Otolaryngology 2014)
- Causes: Regulators accept surrogate endpoints that were never validated for the specific indication.; Sponsors choose control arms, endpoints and populations to maximise the chance of a positive trial rather than to answer the clinical question.; Trials take so long that the standard of care changes before readout.; Duration, dose and sequencing questions have no commercial sponsor.; Per-patient costs, site set-up, monitoring and data management have inflated far faster than the value of the information produced.

## Sources

- Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017): https://doi.org/10.1136/bmj.j4530
- Prasad et al., Strength of association between surrogate endpoints and survival in oncology (JAMA Intern Med 2015): https://doi.org/10.1001/jamainternmed.2015.2829
- FDA Oncology Center of Excellence, Project FrontRunner: https://www.fda.gov/about-fda/oncology-center-excellence/project-frontrunner
- Wouters et al., Estimated research and development investment needed to bring a new medicine to market (JAMA 2020): https://doi.org/10.1001/jama.2020.1166

## Connected records

- collections: [ClinicalTrials.gov](https://onco.cc/collections/clinicaltrials-gov/), [ESMO Clinical Practice Guidelines & MCBS](https://onco.cc/collections/esmo-guidelines/), [FDA Oncology Approvals (OCE) & Novel Drug Approvals](https://onco.cc/collections/fda-approvals/)
- ideas: [A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection](https://onco.cc/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/), [A dose-finding trial for exercise after cancer](https://onco.cc/ideas/idea-nl-exercise-dose-finding/), [A national non-profit contract research organisation for academic oncology trials](https://onco.cc/ideas/idea-fund-public-nonprofit-cro/), [A national platform trial that every ctDNA-positive patient can join](https://onco.cc/ideas/idea-bio2-national-mrd-platform/), [A permanent neutral non-profit sponsor for multi-company platform trials](https://onco.cc/ideas/idea-fund-neutral-platform-sponsor/), [A permanent platform trial for supportive-care interventions inside cooperative groups](https://onco.cc/ideas/idea-moon-supportive-care-platform-trial/), [A perpetual platform trial in every major cancer, funded as infrastructure](https://onco.cc/ideas/idea-tr2-perpetual-platforms/), [A platform trial of very-low-cost metronomic chemotherapy in LMIC common cancers](https://onco.cc/ideas/idea-acc-metronomic-lmic-platform-trial/), [A pre-registered standard for emulating trials with real-world data](https://onco.cc/ideas/idea-data-target-trial-emulation-standard/), [A public fund for trials that test less treatment](https://onco.cc/ideas/idea-tr1-public-de-escalation-trial-fund/), [A public indemnity pool so universities can sponsor first-in-human cancer trials](https://onco.cc/ideas/idea-fund-academic-sponsor-indemnity-pool/), [A public rulebook for when an external or synthetic control arm is acceptable](https://onco.cc/ideas/idea-tr1-external-control-rulebook/), [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/), [A RECOVERY-style permanent platform trial of cheap drugs added to cancer care](https://onco.cc/ideas/idea-reg-recovery-style-platform-repurposing/), [A regulatory endpoint for drugs that block spread, not tumours](https://onco.cc/ideas/idea-bio2-antimetastatic-endpoint/), [A shared library of pooled control arms to shrink and speed future trials](https://onco.cc/ideas/idea-fund-control-arm-commons/), [A short pre-surgery drug window as the default early test of new agents](https://onco.cc/ideas/idea-tr1-window-of-opportunity-default/), [A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling](https://onco.cc/ideas/idea-tr1-tumour-agnostic-approval-standard/), [A standing platform trial for every major cancer, funded as infrastructure](https://onco.cc/ideas/idea-tr1-standing-platform-per-cancer/), [A standing platform trial that assigns treatment by how the tumour escaped](https://onco.cc/ideas/idea-bio1-resistance-platform-trial/), [A trial of sparing the liver resection in peritoneal-side (T2a) gallbladder cancer](https://onco.cc/ideas/idea-gbc-t2a-spare-liver-resection-trial/), [Add a cheap-drug factorial arm to every cooperative-group adjuvant cancer trial](https://onco.cc/ideas/idea-reg-factorial-addon-arms-cooperative-trials/), [Add a drug when the blood test turns, without stopping the one that works](https://onco.cc/ideas/idea-bio1-molecular-progression-add-on/), [After approval, a pragmatic trial in the patients the pivotal trial excluded](https://onco.cc/ideas/idea-tr1-post-approval-pragmatic-trial-in-excluded/), [Aggregated single-patient crossover trials for symptom and supportive treatments](https://onco.cc/ideas/idea-tr1-aggregated-n-of-1-supportive-care/), [Agree in advance how to borrow evidence between similar rare cancers](https://onco.cc/ideas/idea-bio2-bayesian-borrowing-acceptance/), [AI-assisted central imaging reads to cut endpoint cost and variability](https://onco.cc/ideas/idea-tr1-ai-central-imaging-reads/), [An abbreviated approval path for follow-on antibodies within a validated class](https://onco.cc/ideas/idea-fund-abbreviated-pathway-me-too-biologics/), [An independent programme that validates surrogate endpoints, setting by setting](https://onco.cc/ideas/idea-tr1-surrogate-validation-programme/), [Assign first-line treatment in diffuse large B-cell lymphoma by genetic subtype, not by a three-antibody stain](https://onco.cc/ideas/lymphoma-ev-genetic-subtype-directed-first-line/), [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/), [Borrow from past control arms to shrink the control group in phase 3](https://onco.cc/ideas/idea-tr1-bayesian-borrowing-smaller-controls/), [Capture diet, fibre and antibiotic exposure in every immunotherapy pivotal trial](https://onco.cc/ideas/idea-nl-diet-covariates-io-trials/), [Cheap long-term survival follow-up by linking trial participants to registries](https://onco.cc/ideas/idea-tr1-registry-linked-os-followup/), [Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed](https://onco.cc/ideas/idea-pdac-neoadjuvant-chemotherapy-for-all-resectable-disease/), [Chemotherapy before the second operation for high-risk incidental gallbladder cancer](https://onco.cc/ideas/idea-gbc-neoadjuvant-for-high-risk-incidental-cancer/), [Competing sponsors share one control arm in the same indication](https://onco.cc/ideas/idea-tr1-shared-control-arms-across-sponsors/), [Core-funded radiotherapy trials infrastructure with central quality assurance](https://onco.cc/ideas/idea-fund-radiotherapy-trials-infrastructure/), [ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative](https://onco.cc/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/), [Define tolerability endpoints as rigorously as efficacy endpoints](https://onco.cc/ideas/idea-tr1-tolerability-estimands/), [Direct record-to-database data capture: no manual transcription, no full source verification](https://onco.cc/ideas/idea-tr1-esource-ehr-to-edc/), [Embed cachexia treatment in chemotherapy trials: weight, muscle and treatment delivery as co-primary endpoints](https://onco.cc/ideas/idea-pdac-cachexia-trials-embedded-in-chemotherapy-trials/), [Emulate the trial in real-world data first to decide which trials to run](https://onco.cc/ideas/idea-tr1-target-trial-emulation-to-prioritise-rcts/), [Follow every trial participant for 30 years through registry linkage](https://onco.cc/ideas/idea-data-registry-follow-up-of-trial-participants/), [Fund trials that test shorter courses of the most expensive adjuvant drugs](https://onco.cc/ideas/idea-cost-shorter-course-trials/), [Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease](https://onco.cc/ideas/idea-tnbc-de-escalation-for-exceptional-responders/), [Give survivorship interventions a shared control arm](https://onco.cc/ideas/idea-rejuv-survivorship-platform-trial/), [Group trials by broken mechanism, not by organ or single mutation](https://onco.cc/ideas/idea-bio2-mechanism-defined-baskets/), [In silico trials to prioritise combinations, scored against later real trials](https://onco.cc/ideas/idea-data-in-silico-trials-calibrated/), [Joint FDA-EMA-MHRA-PMDA scientific advice by default before pivotal cancer trials](https://onco.cc/ideas/idea-reg-joint-scientific-advice-default/), [Judge a prostate screening programme on metastatic presentation, not on incidence or mortality](https://onco.cc/ideas/idea-prostate-metastatic-presentation-as-the-screening-endpoint/), [Kill combination arms early using circulating tumour DNA, before waiting for scans](https://onco.cc/ideas/idea-tr2-ctdna-futility-gates/), [Let MCED trials read out on late-stage incidence, with mortality follow-up mandated](https://onco.cc/ideas/idea-prev-mced-stage-endpoint-surrogate/), [Let the trial learn: response-adaptive allocation across many combination arms](https://onco.cc/ideas/idea-tr2-bandit-allocation/), [Lock the biomarker cut-off before phase 3, and publish it](https://onco.cc/ideas/idea-tr2-cutpoint-lock/), [Make clonal clearance, not tumour shrinkage, a trial endpoint](https://onco.cc/ideas/idea-bio1-clonal-clearance-endpoint/), [Make sponsors justify every trial exclusion of older and multimorbid patients](https://onco.cc/ideas/idea-acc-broad-eligibility-as-regulatory-default/), [Map trial case report forms to the registry standard so trial and routine data join](https://onco.cc/ideas/idea-data-trial-to-registry-bridge/), [Measure brain metastasis prevention as a primary endpoint, not as a secondary one](https://onco.cc/ideas/idea-lung-brain-metastasis-prevention-as-a-primary-endpoint/), [Metastasis prevention as a formal indication with its own trials and regulatory pathway](https://onco.cc/ideas/idea-moon-metastasis-prevention-indication/), [MRD-guided treatment-free intervals in myeloma](https://onco.cc/ideas/idea-mrd-guided-stop-myeloma/), [Multi-arm, multi-stage trials to answer which order to give approved drugs](https://onco.cc/ideas/idea-tr1-mams-for-sequencing-questions/), [One global rare cancer network with n-of-1 and Bayesian trial frameworks](https://onco.cc/ideas/idea-moon-rare-cancer-global-network/), [One master trial for cancer prevention drugs across many precancers](https://onco.cc/ideas/idea-prev-chemoprevention-master-protocol/), [One standing umbrella trial for all rare cancers in a country](https://onco.cc/ideas/idea-bio2-rare-cancer-umbrella-platform/), [Open-source models that translate stage shift into lives saved, for every cancer](https://onco.cc/ideas/idea-prev-open-stage-shift-microsimulation/), [Open-source protocol and statistical analysis plan templates with runnable code](https://onco.cc/ideas/idea-tr1-open-protocol-and-sap-library/), [Patent term extension scaled to proven survival gain](https://onco.cc/ideas/idea-fund-value-based-patent-extension/), [Patient panels approve trial burden and endpoints as a condition of funding](https://onco.cc/ideas/idea-moon-patient-designed-trials/), [Point-of-care randomisation built into the oncology record](https://onco.cc/ideas/idea-data-point-of-care-randomisation/), [Power trials to detect a benefit patients would value, not the smallest detectable one](https://onco.cc/ideas/idea-tr1-power-for-meaningful-benefit/), [Pragmatic trials in patients over 75 with function, not just survival, as the primary endpoint](https://onco.cc/ideas/idea-acc-pragmatic-trials-over-75-function-endpoints/), [Pre-consented cohorts that can be randomised to future trials (TwiCs)](https://onco.cc/ideas/idea-tr1-pre-consented-cohort-randomisation/), [Pre-specified crossover-adjusted survival in every trial that allows crossover](https://onco.cc/ideas/idea-tr1-crossover-adjusted-survival-standard/), [Pre-surgery platform trials that test combinations on pathological response in months](https://onco.cc/ideas/idea-tr2-neoadjuvant-combo-platform/), [Prevention trials aimed only at brain metastasis](https://onco.cc/ideas/idea-bio2-brain-met-prevention-trials/), [Publish per-patient trial cost benchmarks and target halving them](https://onco.cc/ideas/idea-tr1-public-trial-cost-benchmarks/), [Publish the disagreement between trial doctors and independent reviewers for every trial](https://onco.cc/ideas/idea-tr2-bicr-discordance-public/), [Publish why patients were screened out of each trial](https://onco.cc/ideas/idea-tr1-public-screen-fail-reasons/), [Qualify a physical function endpoint so anti-wasting drugs can be approved](https://onco.cc/ideas/idea-bio2-cachexia-function-endpoint/), [Quantitative patient preference studies set the benefit-risk bar before phase 3](https://onco.cc/ideas/idea-moon-preference-studies-before-phase3/), [Randomise inside the cancer registry: registry-based trials for everyday questions](https://onco.cc/ideas/idea-tr1-registry-embedded-randomisation/), [Randomise inside the registry that already follows every patient](https://onco.cc/ideas/idea-bio2-registry-embedded-randomisation/), [Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint](https://onco.cc/ideas/idea-crc-organ-preservation-randomised-in-pmmr-rectal/), [Randomise the next line of treatment before the first one fails](https://onco.cc/ideas/idea-bio1-pre-randomised-sequencing-trials/), [Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer](https://onco.cc/ideas/idea-prostate-randomise-the-sequence-not-only-the-drugs/), [Randomised trials of stopping immunotherapy after one year versus continuing](https://onco.cc/ideas/idea-tr1-immunotherapy-stop-trials/), [Registry-based randomised trials for oncology comparative effectiveness](https://onco.cc/ideas/idea-data-registry-based-rcts/), [Regulators accept shrinking of precancer as the endpoint for prevention drug approval](https://onco.cc/ideas/idea-prev-precursor-endpoints-for-approval/), [Report gallbladder cancer as its own population in every biliary trial](https://onco.cc/ideas/idea-gbc-report-gallbladder-separately-in-biliary-trials/), [Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote](https://onco.cc/ideas/lymphoma-ev-manufacturing-time-as-a-trial-endpoint/), [Report time toxicity, the days spent in healthcare, as a standard outcome for older patients](https://onco.cc/ideas/idea-acc-time-toxicity-reporting/), [Require a randomised phase 2 before any phase 3](https://onco.cc/ideas/idea-tr1-randomised-phase-2-before-phase-3/), [Require head-to-head trials against the best in class for later entrants](https://onco.cc/ideas/idea-fund-head-to-head-mandate/), [Retire the 3+3: model-based dose finding that counts late and chronic side effects](https://onco.cc/ideas/idea-tr1-model-based-dose-finding-with-late-toxicity/), [Run small-cell lung cancer as one platform with shared controls and subtype stratification](https://onco.cc/ideas/idea-lung-small-cell-platform-with-shared-controls-and-subtypes/), [Seamless phase 2/3 with pre-registered go rules as the default for new agents](https://onco.cc/ideas/idea-tr1-seamless-2-3-with-prespecified-go/), [Select cachexia trial patients by the hormone driving their wasting](https://onco.cc/ideas/idea-bio2-gdf15-stratified-enrolment/), [Select microsatellite stable patients for immunotherapy by a measured immune biomarker, not by how many treatments they have already failed](https://onco.cc/ideas/idea-crc-mss-immunotherapy-by-biomarker-not-by-line/), [SMART designs to test treatment strategies, not just single drugs](https://onco.cc/ideas/idea-tr1-smart-designs-for-adaptive-strategies/), [Standards for external control arms built from federated real-world data](https://onco.cc/ideas/idea-data-external-control-arm-standard/), [Stop excluding brain metastases from cancer trials](https://onco.cc/ideas/idea-bio2-cns-cohort-mandate/), [Stop failing trials earlier with pre-registered aggressive futility rules](https://onco.cc/ideas/idea-tr1-aggressive-futility-boundaries/), [Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint](https://onco.cc/ideas/idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2/), [Test the drug in biomarker-negative patients too, so the biomarker can be validated](https://onco.cc/ideas/idea-tr2-marker-stratified-default/), [Test whether T1b gallbladder cancer needs the second operation at all](https://onco.cc/ideas/idea-gbc-t1b-simple-cholecystectomy-prospective-study/), [Time to treatment failure and quality of life as co-primary endpoints in non-curative trials](https://onco.cc/ideas/idea-tr1-ttf-and-qol-coprimary/), [Tolerability as a co-primary endpoint with its own label claim](https://onco.cc/ideas/idea-moon-toxicity-first-endpoints/), [Trials that include, and report, brain metastases in triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-brain-metastasis-trials/), [Upfront reduced-dose regimens tested head-to-head in frail older patients](https://onco.cc/ideas/idea-acc-upfront-reduced-dose-trials-frail/), [Use a blood test at six weeks to decide whether to keep going](https://onco.cc/ideas/idea-bio2-ctdna-six-week-io-switch/), [Use circulating tumour DNA instead of the interim scan to decide what happens next](https://onco.cc/ideas/lymphoma-ev-ctdna-instead-of-the-interim-scan/), [Use pre-surgery immunotherapy windows as the field's biomarker engine](https://onco.cc/ideas/idea-bio2-neoadjuvant-biomarker-engine/), [Use tumour DNA in blood to decide when to pause treatment in metastatic cancer](https://onco.cc/ideas/idea-tr1-ctdna-guided-stop-in-metastatic-disease/), [Validate real-world progression endpoints so pragmatic trials can use them](https://onco.cc/ideas/idea-tr1-validate-real-world-progression-endpoints/), [Win-ratio endpoints that weigh survival, toxicity and quality of life together](https://onco.cc/ideas/idea-tr1-win-ratio-net-benefit-endpoint/)
- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [AI trial matching & clinical decision support](https://onco.cc/technologies/ai-trial-matching/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [PRO-CTCAE: side effects graded by the person having them](https://onco.cc/technologies/rejuv-measure-pro-ctcae/), [The questionnaires that were never returned, and the people never asked](https://onco.cc/technologies/rejuv-measure-missing-data-and-who-is-not-asked/), [What a difference has to be before a person would notice it](https://onco.cc/technologies/rejuv-measure-minimally-important-difference/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [Duke Cancer Institute](https://onco.cc/institutions/duke-cancer-institute/), [European Society for Medical Oncology (ESMO)](https://onco.cc/institutions/esmo/), [Juravinski Cancer Centre / Escarpment Cancer Research Institute](https://onco.cc/institutions/juravinski/), [National Cancer Institute (NIH)](https://onco.cc/institutions/nci/), [The Ottawa Hospital Cancer Centre / Ottawa Hospital Research Institute](https://onco.cc/institutions/ottawa-hospital/), [University Hospitals Birmingham / University of Birmingham Cancer Research Centre](https://onco.cc/institutions/birmingham-cancer-centre/)
- terms: [Accelerated approval](https://onco.cc/terms/accelerated-approval/), [Basket trial](https://onco.cc/terms/basket-trial/), [Basket, umbrella, and platform trials](https://onco.cc/terms/basket-umbrella-platform/), [Bayesian trial design](https://onco.cc/terms/bayesian-trial-design/), [Bipolar androgen therapy (BAT)](https://onco.cc/terms/bipolar-androgen-therapy/), [Enrichment and biomarker-stratified designs](https://onco.cc/terms/biomarker-stratified-design/), [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [FDORA 2022 accelerated approval reforms](https://onco.cc/terms/fdora-2022/), [Federal Food, Drug, and Cosmetic Act and the Kefauver-Harris Amendments](https://onco.cc/terms/fdca/), [Hazard ratio (HR)](https://onco.cc/terms/hazard-ratio/), [Intermittent androgen deprivation (IAD)](https://onco.cc/terms/intermittent-androgen-deprivation/), [Japan conditional early approval and time-limited approval](https://onco.cc/terms/japan-conditional-early-approval/), [Lead time, and lead-time bias](https://onco.cc/terms/lead-time-bias/), [Master protocol (platform, basket and umbrella trials)](https://onco.cc/terms/master-protocol/), [Metastasis-free survival (MFS)](https://onco.cc/terms/metastasis-free-survival/), [MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)](https://onco.cc/terms/mrd-negativity-myeloma/), [Non-inferiority margin and equivalence trials](https://onco.cc/terms/non-inferiority-margin/), [Number needed to screen (and number needed to diagnose)](https://onco.cc/terms/number-needed-to-screen/), [Objective response rate (ORR)](https://onco.cc/terms/orr/), [Overall survival (OS)](https://onco.cc/terms/os/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/), [Project FrontRunner](https://onco.cc/terms/project-frontrunner/), [Quality-adjusted survival (QALYs and Q-TWiST)](https://onco.cc/terms/quality-adjusted-survival/), [Radiographic progression-free survival (rPFS)](https://onco.cc/terms/radiographic-progression-free-survival/), [Real-world evidence](https://onco.cc/terms/real-world-evidence/), [Response-adaptive randomisation](https://onco.cc/terms/response-adaptive-randomisation/), [SMART design (sequential multiple assignment randomised trial)](https://onco.cc/terms/smart-design/), [Statistical power, sample size and re-estimation](https://onco.cc/terms/sample-size-re-estimation/), [Surrogate endpoint validation: which stand-ins have earned trust](https://onco.cc/terms/surrogate-validation/), [Trial lifecycle: from protocol to label](https://onco.cc/terms/trial-lifecycle/), [Umbrella trial](https://onco.cc/terms/umbrella-trial/), [Why trials fail: underpowered, wrong endpoint, control arm drift, subgroup fishing, crossover](https://onco.cc/terms/trial-failure-modes/)
- trials: [Alliance/CALGB 50303](https://onco.cc/trials/calgb-50303/), [Beat AML Master Trial](https://onco.cc/trials/beat-aml-master-trial/), [ComboMATCH (EAY191)](https://onco.cc/trials/combomatch/), [FOCUS4](https://onco.cc/trials/focus4/), [GBM AGILE](https://onco.cc/trials/gbm-agile/), [I-PREDICT](https://onco.cc/trials/i-predict/), [Lung-MAP (SWOG S1400 and S1900)](https://onco.cc/trials/lung-map/), [Mosunetuzumab against rituximab in low tumour burden follicular lymphoma](https://onco.cc/trials/mosun-lbt-fl/), [myeloMATCH](https://onco.cc/trials/myelomatch/), [National Lung Matrix Trial](https://onco.cc/trials/national-lung-matrix-trial/), [NCI-COG Pediatric MATCH (APEC1621)](https://onco.cc/trials/pediatric-match/), [NCI-MATCH (EAY131)](https://onco.cc/trials/nci-match/), [Precision Promise](https://onco.cc/trials/precision-promise/), [STAMPEDE](https://onco.cc/trials/stampede/), [TAPUR (Targeted Agent and Profiling Utilization Registry)](https://onco.cc/trials/tapur/)
- key papers: [A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications](https://onco.cc/key-papers/paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020/), [Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study (QUASAR)](https://onco.cc/key-papers/paper-quasar-adjuvant-chemotherapy-vs-observation-lancet-2007/), [Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13](https://onco.cc/key-papers/paper-davis-bmj/), [CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint](https://onco.cc/key-papers/paper-cepheus-dara-vrd-natmed-2025/), [CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery](https://onco.cc/key-papers/paper-checkmate-816-nejm-2022/), [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/), [Children's Oncology Group AALL1731: blinatumomab added to chemotherapy for children with standard-risk B-cell ALL](https://onco.cc/key-papers/paper-aall1731-blinatumomab-children-nejm-2025/), [CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug](https://onco.cc/key-papers/paper-codebreak-200-lancet-2023/), [Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer](https://onco.cc/key-papers/paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002/), [DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer](https://onco.cc/key-papers/paper-destiny-breast06-nejm-2024/), [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/), [DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer](https://onco.cc/key-papers/paper-dynamic-nejm-2022/), [Early relapse of follicular lymphoma after R-CHOP defines patients at high risk for death: an analysis from the National LymphoCare Study](https://onco.cc/key-papers/paper-casulo-pod24-follicular-lymphoma-jco-2015/), [Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018](https://onco.cc/key-papers/paper-wouters-jama/), [First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers](https://onco.cc/key-papers/paper-lynch-frameshift-vaccine-ccr-2020/), [Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma](https://onco.cc/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/), [Genetics and pathogenesis of diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018/), [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/), [IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery](https://onco.cc/key-papers/paper-imvigor011-nejm-2025/), [INDIGO: vorasidenib, the first targeted drug for IDH-mutant low-grade glioma](https://onco.cc/key-papers/paper-indigo-nejm-2023/), [KarMMa-3: ide-cel CAR-T versus standard regimens in triple-class-exposed relapsed myeloma](https://onco.cc/key-papers/paper-karmma-3-ide-cel-nejm-2023/), [KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment](https://onco.cc/key-papers/paper-katherine-nejm-2019/), [KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer](https://onco.cc/key-papers/paper-keynote-177-nejm-2020/), [KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery](https://onco.cc/key-papers/paper-keynote-942-lancet-2024/), [Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group](https://onco.cc/key-papers/paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008/), [Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data](https://onco.cc/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/), [NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma](https://onco.cc/key-papers/paper-nadina-nejm-2024/), [Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial](https://onco.cc/key-papers/paper-preopanc-2-neoadjuvant-folfirinox-vs-chemoradiotherapy-lancet-oncol-2025/), [NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours](https://onco.cc/key-papers/paper-netter-2-lancet-2024/), [NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test](https://onco.cc/key-papers/paper-nhs-galleri-design-cancers-2022/), [NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer](https://onco.cc/key-papers/paper-niagara-nejm-2024/), [NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients](https://onco.cc/key-papers/paper-niche-2-nejm-2024/), [Optimal surgical treatment in patients with T1b gallbladder cancer: An international multicenter study](https://onco.cc/key-papers/paper-kim-t1b-gallbladder-cancer-international-jhbps-2018/), [Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis](https://onco.cc/key-papers/paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014/), [Perioperative durvalumab for resectable non-small-cell lung cancer](https://onco.cc/key-papers/paper-heymach-aegean-perioperative-durvalumab-nejm-2023/), [Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer](https://onco.cc/key-papers/paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023/), [PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma](https://onco.cc/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/), [PLCO: mortality results from a randomised prostate cancer screening trial](https://onco.cc/key-papers/paper-andriole-plco-prostate-screening-nejm-2009/), [Prasad: most surrogate endpoints in cancer trials correlate poorly with survival](https://onco.cc/key-papers/paper-prasad-surrogate-endpoints-jama-im-2015/), [PREDIMED: a Mediterranean diet with extra-virgin olive oil and fewer breast cancers](https://onco.cc/key-papers/paper-predimed-breast-jama-im-2015/), [Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer](https://onco.cc/key-papers/paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023/), [Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma](https://onco.cc/key-papers/paper-belinda-tisagenlecleucel-second-line-nejm-2022/), [STAMPEDE: adding abiraterone to hormone therapy at diagnosis of advanced prostate cancer](https://onco.cc/key-papers/paper-stampede-abiraterone-nejm-2017/), [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/), [SunRISe-1: TAR-200, a gemcitabine-releasing device placed in the bladder, for BCG-unresponsive non-muscle-invasive bladder cancer](https://onco.cc/key-papers/paper-sunrise-1-jco-2025/), [SWOG 9346: intermittent versus continuous androgen deprivation in metastatic prostate cancer](https://onco.cc/key-papers/paper-hussain-swog-9346-intermittent-androgen-deprivation-nejm-2013/), [SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults](https://onco.cc/key-papers/paper-swog-s1826-nivolumab-avd-nejm-2024/), [TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021/), [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/), [VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer](https://onco.cc/key-papers/paper-vision-nejm-2021/)
- roadmaps: [Devices and physical therapies roadmap: heat and light → electric fields and focused sound → drug-releasing implants](https://onco.cc/roadmaps/devices-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/), [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/), [Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH](https://onco.cc/roadmaps/radiation-roadmap/), [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/)
- people: [Bernard Fisher](https://onco.cc/people/bernard-fisher/), [Fran Visco](https://onco.cc/people/fran-visco/), [Rose Kushner](https://onco.cc/people/rose-kushner/)

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