Table 4 Problems in the implementation process of clinical trials

 Subject

Number

Item

  Design

1

Templated content [58, 84]

2

Insufficient information and incorrect version [38, 40, 54, 58, 69, 76, 86]

3

Incomprehensive description of insurance and compensation [8, 40, 84]

4

Unreviewed and unapproved by the ethics committee [70, 86]

  Implementation

5

Nonstandard informed consent signing and writing [24, 38, 54, 63, 85, 86]

6

Lack of contact information and signing date [32, 80, 84]

7

Deficient notification [58]

8

Selective or induced notification [28, 38, 58, 70, 85, 86]

9

Inappropriate place of notification [85]

10

Unprovided copy of the informed consent to the patient [32, 41, 54, 84]

11

Absence of informed consent signed by screening subjects [80]

12

Informed consent process is not reflected in the original medical record [32]

 Subject

Number

Item

  Implementation

1

Unstrict execution of inclusion and exclusion criteria [19, 25, 32, 46, 63, 64, 75, 77, 78, 80, 81]

2

Administration of drugs not in accordance with dosage specified in the protocol [77, 80]

3

Premature or delayed assessment [32, 46, 57, 60, 75, 80]

4

Time-overlapping between informed consent, screening, enrolment, and administration of drugs [24]

  Record

5

Taking unspecified drugs and not recorded or not recorded on time [24]

6

Incomplete documentation of clinical trials process [39]

7

The signing time of the corresponding task assignment form, training record form, and the protocol signing page did not conform to the actual situation when the researchers change or the task assignment changes [24]

 Subject

Number

Item

  Inspectors

1

Inadequate execution of tertiary quality controls [44, 50, 61, 87]

2

Insufficient competence and responsibility of the inspectors [36, 49, 56, 87]

 Subject

Number

Item

  Implementation

1

Nonstandard management in experimental drugs receipting, distribution, storage, recycling, and destruction [24, 42, 53, 59]

2

No standard for the label of experimental drugs [59]

3

Nonstandard records of drug administration [63, 79]

4

The information of drug administration forms does not match with the records in original medical reports and case report forms [24, 79]

5

The records do not present the actual dosage of drugs [32]

6

The drug dosage and specifications recorded in drug release form are not matched with the reality [32, 80]

7

Researchers lack knowledge on quality management practices in drug clinical trials [33, 47, 80]

 Subject

Number

Item

  Implementation

1

Nonstandard record and revision of case report form [25]

2

Missing or incomplete records of drug combination [32, 57]

3

Inconsistent data records with primary material [32, 51, 77, 80]

4

Data is not recorded in the medical records or not recorded in time [25]

5

Data is untraceable, irregular, omitted, and concealed records of adverse events in trials [32, 80]

6

Incomplete records of the reports [32, 74]

 Subject

Number

Item

  Judgment

1

Absence of risk prediction, prevention mechanism, and treatment for serious adverse events in the study protocol [55]

2

Confuse clinical trials with clinical treatment [35]

3

Absence of report on adverse events [55]

4

Delayed time in submission of report on adverse events [23, 34, 35, 55]

5

Misjudgment of abnormal inspection results [35]

6

No dynamic observation on inspection results [35]

7

Misjudgment of the causal relationship between adverse events and experimental drugs [35]

  Record

8

Nonstandard report of adverse events, including deferred report and improper writing of report form [34, 55]

9

Incomplete original records [35]

10

Incomplete receipt collection [34]

11

Special circumstances are not noted [34]

 Subject

Number

Item

  Implementation

1

Inadequate collection, storage, transportation, and handover records of biological sample [24, 77]

  Record

2

Disorder timeline of records in sample collection, inspection, and audit process [24]

 Subject

Number

Item

  Coordinator

1

Uneven ability of clinical research coordinators [48, 66]

  System

2

Imperfect construction of management organization system [37, 48]

3

Incomplete training and assessment mechanism [37, 66]

4

Lacking unified management system [37, 66]

 Subject

Number

Item

  Contract

1

No standards and principles for reviewing clinical trials protocols [45]

2

No legal professional participant in review of clinical trials contract [31]

3

Unclear injury compensation liability of participants [31, 43, 45, 79]

4

Unreasonable clauses involving termination, confidentiality, and intellectual property ownership [31]

5

Low purchase rate of clinical trials insurance cause the rights and interests of subjects and researchers cannot be fully protected [52]

6

Trials contracts contain missing clauses, including description of clinical trials costs, contract signatory, and responsibilities of all parties [31]