UMIN-CTR Clinical Trial

Public title

Detection bias in open-label trials of cancer drug: a meta-epidemiologic study

Acronym

Detection bias in open-label trials of cancer drug: a meta-epidemiologic study

Scientific Title

Detection bias in open-label trials of cancer drug: a meta-epidemiologic study

Scientific Title:Acronym

Detection bias in open-label trials of cancer drug: a meta-epidemiologic study

Region

Japan	Asia(except Japan)	North America
South America	Australia	Europe
Africa

Condition

Open-label trials of cancer drug assessed by both blinded and nonblinded adjudicators.

Classification by specialty

Not applicable

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate detection bias in open-label trials of cancer drugs.

Basic objectives2

Others

Basic objectives -Others

No

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Ratio of hazard ratio (RHR: HRnonblinded by HRblinded) of progression free survival (PFS)

Key secondary outcomes

Ratio of odds ratio (ROR: ORnonblinded by ORblinded) of objective response ratio (ORR)

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Randomized, controlled, open-label, parallel-group superiority trials investigating the efficacy of anticancer agents. Included cancers are focused on breast, lung, colorectal, prostate, stomach and kidney cancers.

Key exclusion criteria

Blinded, non-inferiority, equivalence, and single-arm trials.

Target sample size

0

Name of lead principal investigator

1st name	Satoshi
Middle name	Funada
Last name	Funada

Organization

Kyoto University

Division name

Department of Health Promotion and Human Behavior, Kyoto University School of Public Health

Zip code

606-8501

Address

Yoshida Konoe-cho, Sakyo-ku, Kyoto

TEL

075-753-9492

Email

sfunada@kuhp.kyoto-u.ac.jp

Name of contact person

1st name	Satoshi
Middle name	Funada
Last name	Funada

Organization

Kyoto University

Division name

Department of Health Promotion and Human Behavior, Kyoto University School of Public Health

Zip code

606-8501

Address

Yoshida Konoe-cho, Sakyo-ku, Kyoto

TEL

075-753-9492

Homepage URL

Email

sfunada@kuhp.kyoto-u.ac.jp

Institute

Department of Health Promotion and Human Behavior, Kyoto University School of Public Health

Institute

Department

Personal name

Organization

No

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Kyoto University Graduate School and Faculty of Medicine, Ethics Committee

Address

Yoshida Konoe-cho, Sakyo-ku, Kyoto

Tel

075-753-4680

Email

ethcom@kuhp.kyoto-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2021

Year

06

Month

22

Day

URL releasing protocol

https://osf.io/csx7h/

Publication of results

Published

URL related to results and publications

https://ebm.bmj.com/content/early/2023/08/16/bmjebm-2023-112332.long

Number of participants that the trial has enrolled

114

Results

We retrieved 1197 records of oncological open-label trials after full-text screening. We identified 171 records (PFS: 149 records, ORR: 136 records) in which both central reviewers and local investigators were used, and included 114 records (PFS: 92 records, ORR: 74 records) for meta-analyses. While the RHR for PFS was 0.95 (95% CI 0.91 to 0.98), the ROR of ORR was 1.00 (95% CI 0.91 to 1.09). The results remained unchanged in the prespecified sensitivity analysis.

Results date posted

2023

Year

08

Month

28

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The analysis included 114 records, 92 for PFS and 74 for ORR. The majority of the trials were phase III (n=74); the most common tumour types were non-small cell lung cancer (n=29), breast cancer (n=22) and renal cell cancer (n=14); and the most common type of drug was targeted therapy (n=70). PFS was the primary outcome in 82 records, whereas ORR was the primary outcome in 13. Most of the reports were from high-impact factor (>10) journals (n=102), with only 5 funded by the public sector.

Participant flow

We identified 6339 records, 1517 of which were eligible after screening titles and abstracts. From 1517 records, we retrieved 1197 eligible records after full-text screening and assessed the adjudicators of PFS and ORR. A total of 181 records (PFS: 157 records, ORR: 141 records) were adjudicated by both central reviewers and local investigators (online supplemental table 1), and the trend of the prevalence of outcome adjudicators did not change from 2010 to 2021 in both PFS (online supplemental figure 2) and ORR (online supplemental figure 3). Of the 181 records, we excluded 10 due to data duplication and included the remaining records that could extract the outcomes adjudicated by both central reviewers and local investigators. Finally, we included 114 records in this analysis, of which 92 were analysed for PFS and 74 for ORR. In other words, among the records that we judged were adjudicated by both central reviewers and local investigators for PFS, only 61.7% (92/149) reported results from both assessors and 54.4% (74/136) for ORR. Online supplemental materials list the exclusion criteria for records during the full-text screening stage (n=320), data extraction stage (n=57) and duplication records stage (n=10). We sent 121 emails to the corresponding authors to request details of the data (26 October 2022) and received 15 responses, of which only one provided sufficient information. The other 14 corresponding authors stated that they could not access the data.

Adverse events

NA

Outcome measures

Ratio of hazard ratio (RHR)
Ratio of odds ratio (ROR)

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2021

Year

06

Month

25

Day

Date of IRB

2021

Year

06

Month

25

Day

Anticipated trial start date

2021

Year

07

Month

01

Day

Last follow-up date

2022

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

We will perform a meta-analysis of RHR and ROR with inverse variance methods using a random-effect model. We will also perform sensitivity analysis and subgroup analysis.

Registered date

2021

Year

06

Month

22

Day

Last modified on

2023

Year

08

Month

28

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050668