Related Works

Used Categories

• Accrual issues
• Demonstrated efficacy
• Toxicity
• Funding and/or drug supply
• Lack of efficacy
• Other, multiple reasons, or unknown

Trial Selection

Oncological intervention trials registered from 27.09.2007 to 30.06.2015 (n=9,497)
	Excluded: Cancer not condition studied (n=309) Not exclusively oncology focused (n=95) Not all cancer patients (n=141) No intervention on patients (n=4) Withdrawn studies (n=261)
Included trials (n=8,687)
	Non-terminated trials (n=6,712)
Terminated trials (n=1,975)

Used Categories

• participant accrual difficulties
• administrative or financial reasons
• futility, or changes in risk/ benefit profile
• sponsor decisions
• treatment recall
• study replacement or changes in standard of care
• COVID-19 pandemic–related
• other or unspecified reasons

Used Categories

• insufficient participant accrual rate
• business decision or strategic reasons (eg, sponsor decision, change in clinical strategy)
• regulatory or conduct issues (eg, protocol compliance or siterelated issues, expiration of IRB approval)
• scientific data from trial (eg, lack of efficacy, unfavorable riskbenefit profile)
• sufficient participant recruitment for analysis
• recall or cessation of production of the investigational product
• inadequate funding/resources
• reasons related to the coronavirus disease 2019 (COVID-19) pandemic (eg, laboratory shutdown, safety restrictions)
• external information (eg, changes in standard of care or data from other trials resulted in the study becoming inconsequential)
• unclear reasons or reason missing (ie, not reported to ClinicalTrials.gov by either the sponsor or principal investigator)

Trial Selection

All clinical trials to date at ClinicalTrials.gov with one of the following search terms for condition/disease of the spine were identified: Spine Degeneration, Spine Stiffness, Spine Cancer, Spine Fusion, Spine Disease, Spine Infection, Spine Metastases, Spine Injury, Spine Fracture, and Spine Osteoarthritis. Those with the designation of completed or terminated were then grouped. (n=969)
	Trials with the designation of completed (n=833)
Trials with the designation of terminated (n=136)

Used Categories

• Business reasons or funding ceased
• Efficacy and/or toxicity issues
• Insufficient accrual (includes insufficient accrual due to: competing studies, clinicians not supporting the trial, scientific advances in other disciplines, new study has been started in similar indication)
• Unknown
• Other reasons

Trial Selection

Interventional phase III trials with the condition "neoplasm", submitted later than 01/2006, updated prior to 05/2017 (n=4,903)
	Completed trials (n=1,383)
Terminated trials [n=371] and Permanently suspended trials ≥ 1.5 years [n=11] (n=382)

Used Categories

• recruitment problems
• funding/resource problems
• departure of the principal investigator from the institution
• lack of efficacy
• study design problems
• administrative reason
• interim analysis results

Trial Selection

Trials with "condition or disease" field terms "Obsessive Compulsive Disorder", "Compulsive Disorder", and "OCD"
	registration date beyond May 7, 2020 or non-interventional
interventional studies registered up to May 7, 2020
	Studies in which OCD is only one of the symptoms of diseases, such as anxiety disorder, depressive disorder, and Tourette syndrome. Studies on hoarding disorder that belongs to the category of Obsessive-Compulsive and Related Disorders.
identified OCD trials (n=298)
	Completed trials (n=270)
Trials discontinued early: suspended [n=2], terminated [n=17], withdrawn [n=9] (n=28)

Used Categories

• Benefit
• Harm
• Futility
• Newly available evidence
• Logistical issues - Slow Enrollment
• Logistical issues - Lack of Money
• Other

Trial Selection

Records identified through database searching (MEDLINE) (n=1,211) Records from other sources (snowballing, known to authors) (n=8) All records screened (n=1,219)
	Records excluded (i.e., clearly not relevant) (n=1,029)
Full-text articles assessed for eligibility (n=190)
	Full-text articles excluded, with reasons (n=94) Manuscript did not report the primary results of an RCT (n=46) Not a phase 2/3 trial with a preplanned sample size >= 100 patients (n=24) Did not enroll stroke patients within one month of onset (n=11) Did not test a therapeutic initiated within 1 month of onset (n=13)
Studies included in qualitative synthesis (n=96)

Used Categories

• poor accrual
• interim results
• toxicity/adverse events
• study agent unavailable
• canceled by the sponsor
• inadequate budget
• logistics
• trial no longer needed
• principal investigator left
• no reason given
• other

Used Categories

• Based on scientific data (efficacy and safety)
  • Basis of the low probability of meeting primary efficacy endpoint
  • Lack of efficacy
  • Safety issues with the development product
  • The study could not be completed on clinical grounds
• Based on other than scientific data from the trial
  • Unable to obtain health authority approval
  • Administrative and business reasons
  • Health authority approval after completion of trial globally
  • Change in the direction of development
  • Poor accrual rate
  • A significant delay in recruitment
  • Protocol needed amendments
  • Did not recruit patients because of conditional approval by health authorities
  • Insufficient funds
  • Internal project and operational aspects
  • Difficulty in procuring ingredients
• Unspecified reasons
  • The trial did not start
  • The sponsor decided to stop the trial
  • No subjects were screened in India

Used Categories

• Not related to Minimizing Volunteer Risk
  • Lack of drug supply
  • Funding
  • Trial administration or conduct
  • Insufficient recruitment rate
  • Other Reason Not Based on Trial Data
  • Unspecified business decision
  • Not specified
• Associated with Minimizing Volunteer Risk
  • Other Reason Based on Trial Data
  • Drug was not FDA approved
  • Clinical Hold
  • Changing Care Landscape
  • Emerging Data
  • Futility
  • Efficacy
  • Safety

Trial Selection

All Studies Posted in ClinicalTrials.gov 01/2013-08/2017 (n=105,239)
	Exclude All Study Type Defined As Observational or Expanded Access
All Interventional Studies Posted in ClinicalTrials.gov (n=82,395)
	Exclude All Study PHase Defined as: Early Phase 1, Phase 1, Phase 2, Phase 4, Unknown
All Phase 3 Interventional Studies Posted in ClinicalTrials.gov (n=9,828)
	Exclude All Study Status Defined as: Not recruiting, Recruiting, Enrolling, Active, Suspended, Completed, Withdrawn, Unknown
Phase 3 Terminated Interventional Studies Posted in ClinicalTrials.gov (n=320)
	Exclude 2 bococizumab clinical trials to reduce skewing of participant numbers
Phase 3 Terminated Interventional Studies Posted in ClinicalTrials.gov (n=318)

Used Categories

• Recruitment issues
• Sponsor (strategic or business) decision
• Interim analysis results
• Funding issues
• Safety issues
• Moved study location or investigator moved
• Limited time or clinical capacity
• Ethical approval lapsed
• Study materials expired
• Other
• Not stated

Used Categories

• poor accrual
• lack of efficacy
• toxicity (side effects/adverse events)
• logistical reasons (e.g., insufficient funding, lack of study drug, principal investigator left institution, cancellation by sponsor)
• inadequate study design/trial not necessary (proven efficacy/existence of a similar trial making the current trial unnecessary)

Used Categories

• Funding issues
• Insufficient accrual rate
• Drug supply issues
• Trial Administration or Conduct (issues with protocol, investigators, site)
• Safety/toxicity issues
• Interim results (positive, negative, inconclusive)
• External information
• Sponsor decision/business decision/strategic reasons
• blank
• uninformative response
• misuse of website categories or statuses
• IRB issues
• product withdrawal

Trial Selection

All Studies Posted on ClinicalTrials.gov Results Database as of 2/19/2013 (n=8,197)
	Study Type = Observational (n=551)
Study Type = Interventional (n=7,646)
	Overall Recruitment Status ≠ Terminated AND Enrollment = 0 participants (n=6,741)
Overall Recruitment Status = Terminated AND Enrollment ≥ 1 participant (n=905)

Used Categories

• low recruitment
• safety or ethics issues
• sponsor or business decisions
• financial or administrative reasons
• futility
• benefit
• study competition or replaced for another study
• treatment withdrawn from the market
• other reasons

Trial Selection

Cardiovascular Clinical Trials identified from the registry at ClinicalTrials.gov (n=7,042)
	Excluded after refined search by MeSH and non-MeSH cardiovascular condition terms (n=763)
Selected trials (n=6,279)
	Completed trials (n=5,595)
Terminated trials (n=684)

Used Categories

• Poor Accrual
• Logistics
  • Cancellation of Trial by Sponsor
  • Inadequate Budget
  • Unavailability of Study Agent
  • Departure of Principal Investigator from Institution
• Toxicity / Efficacy
  • Poor Results at Interim Analysis
  • Toxicity/Adverse Events
• Other
  • None Given
  • Other
  • No Longer Necessary

Trial Selection

12,852 trials were assessed for eligibility
	1,901: start date before 9/13/2005 1,652: start date after 11/15/2011 159: start date not listed
9,140 trials coded for condition
	967: non-cancer condition
8,173 trials examined for status
	86: "suspended" status
8,087 trials examined for age eligibility
	311: primarily pediatric trials
7,776 trials included in the analysis

Used Categories

• Based on data accumulated from the trial
  • Unequivocal evidence of treatment benefit or harm
  • Unacceptable side-effects
  • No emerging trends and no reasonable chance of demonstrating benefit
• Based on overall progress of the trial
  • Failure to include enough patients at a sufficient rate
  • Lack of compliance in a large number of patients
  • Insufficient funding
• Based on external information
  • Data from other trials establishing unequivocal treatment benefit or harm
  • Data from clinical practice indicating unsuspected and unacceptable treatment side-effects
  • Developments superseding current treatment
  • Treatment withdrawal from the market