By:Mukesh Kumar Jaiswal

Falsification of data in proposing, designing, performing, recording, supervising or reviewing research, or in reporting research results.

Falsification includes both acts of omission (consciously not revealing all data) and commission (consciously altering or fabricating data)

Fraud does not include honest error Deliberate or repeated noncompliance with the

protocol and GCP can be considered fraud.

Investigators Study coordinators Data management personnel Lab personnel IRB staff CRAs and sponsor personnel FDA

Study Coordinator

Nurse

Hospital

Sponsor

Investigator

Office Staff

Sub-investigator

CRA

39%

17%9%

9%

9%

9%

4% 4%

Difficult to determine but still considered rare Reported to significantly impact 1-5% of

pharmaceutical clinical trials. Only ~3% of FDA inspections uncover serious

GCP violations resulting in Warning Letters

Sponsor – data validity compromised, submission jeopardized, additional costs

Investigator – fines, legal expenses, disqualification/debarment, license revocation, ruined career

Institution – lawsuits Subject – safety at risk, loss of trust in clinical

trial process

Lack of resources (staff, time, subjects) Lack of GCP training Lack of regulatory oversight Laziness Loss of interest Pressure to perform or to publish Money, greed

High staff turnover Staff are disgruntled, fearful, anxious,

depressed, defensive High pressure work environment Obsession with study payments Absent investigators Lack of GCP training Unusually fast recruitment

Implausible trends/patterns:

100% drug compliance

Identical lab/ECG results

No SAEs reported

Subjects adhering perfectly to a visit schedule

Perfect efficacy responses for all subjects

Site data not consistent with other centers (statistical outlier)

Source records lack an audit trail - no signatures and dates of persons completing documentation

All source records & CRFs completed with the same pen

Perfect diary cards, immaculate CRFs

Subject handwriting and signatures are inconsistent across documents

Questionable subject visit dates (Sundays, holidays, staff vacations)

Impossible events (eg, subject randomized before IP even available at the site)

Subject visits cannot be verified in the medical chart or appointment schedule

Data contains “digit preference” – some digits used more frequently than others (0, 5, and even digits)

Expect fraud – start from the assumption that records are bogus.

Question missing, altered, and/or inconsistent data – offer to retrieve records yourself, keep pulling on loose ends.

Don’t be intimidated – challenge to explain suspicious data

Be suspicious of blame shifting –remind the investigator that he/she is responsible for study conduct.

Cultivate whistleblowers – pay attention to staff complaints, establish rapport, and be approachable.

Many fraud cases uncovered by staff whistleblowers

Ethical commitment to report fraud: I recognize my right and responsibility as a clinical

research professional to question suspected falsified data, and if necessary, proceed with appropriate reporting procedures as mandated by the appropriate regulatory agencies.

Many institutions have an Office of Compliance with reporting hotlines

During pre-study evaluation, sponsors should carefully scrutinize sites for interest in the study, stability of the staff, investigator/staff interactions, workload, and level of training.

Everyone involved in the clinical trial process should complete regular GCP training.

CRAs should be expert on the protocol particularly with parameters that determine eligibility (inclusion/exclusion criteria) and primary efficacy endpoints

Sponsors should emphasize their policy on fraud at the initiation visit

Institutions should set-up systems to encourage fraud reporting and protect whistleblowers