Lessons learned

New efforts must be developed to improve human research safety and to reinforce clinical investigators' responsibility in the conduct of clinical research. Companies, institutional review boards, and clinical investigators must work in a collaborative manner to develop new policies on the prevention and detection of clinical research misconduct. Protection must be offered to persons identifying scientific misconduct. The whistleblower is an essential element in the effort to protect the integrity of clinical research, because researchers do not call attention to their own behaviour. Before making an allegation of research misconduct, a whistleblower should understand carefully to whom the allegation should be reported, what protections are provided for the whistleblower, and what part the whistleblower will play in future proceedings.

There are no specific rules for the detection of scientific misconduct and fraud. Nevertheless enhanced compliance with quality-orientated regulatory requirements for study conduct, reporting, and monitoring should allow its early detection. The quality-orientated regulatory requirements include clinical investigator and sponsor responsibilities. The former entails the conduct of the study performed in accordance with the protocol (21 CFR 312.60) and the maintenance of adequate and accurate case histories (21 CFR 312.62[b]). Protocol compliance requires the selection of a qualified clinical investigator and study coordinators as well as a commitment to continuous training and education. The sponsor requirements include proper monitoring of investigations (21 CFR 312.50), monitoring the progress of all clinical investigations being conducted under its IND (21 CFR 312.56[a]), and correcting and/or reporting serious non-compliance to the FDA (21 CFR 312.56[b]).

Failure to follow the protocol and to maintain adequate case histories continue to be the most frequently encountered FDA findings. Investigators must know that the data will be challenged both by regulators and the sponsor. Missing records may be a key indicator of potential fraud. The integrity of clinical data requires original source documentation.

Sponsors need to provide adequate monitoring and independent quality assurance of their clinical trials including:

• adequate sampling of study sites;

• adequate sampling of time points throughout the trial;

• source data verification of data with no reliance on shadow records (that is, document what you did and did not do - if it is not documented, it did not happen);

• frequent monitoring and QA visits to resolve problems early;

• working together with contract research organisations to resolve differences.

Sponsors should:

• select exemplary investigators (qualified, experienced, interested, patient, committed, and able to deliver on time);

• review FDA inspectional information and select investigators who lack serious regulatory and protocol compliance issues and have corrected previous FDA observations;

• educate and train clinical investigators at preclinical investigation meetings as well as investigator responsibilities;

• select qualified, knowledgeable, and reliable contract research organisations (CROs) and monitors;

• review FDA inspectional material.

Identification of scientific misconduct requires the preparation of a complaint handling system by both sponsors and investigators to capture, document, and deal with complaints of misconduct in a timely manner. The procedures for complaint handling should be defined in a policy (that is, Standard Operating Procedure document) that relates to the receiving, reviewing, reporting, and processing of complaints. Confidentiality of the whistleblower should be described. All complaints should be assumed to be credible unless demonstrated to the contrary after thorough evaluation and supervisory review and approval. Follow-up activities are required for all complaints and should be categorised on the basis of the highest priority of reports related to gross abuse of subjects' rights that result or have the potential to result in death or injury. The system should be carefully monitored to ensure timely evaluation and final resolution. The FDA believes that complaints should be reported whenever there is a discovery of misconduct and not delayed when the clinical investigator has been dismissed. Clinical research team members are encouraged to recognise and report research misconduct to government agencies.

Recognising scientific misconduct and fraud requires education and training. In addition to understanding current trial regulations and responsibilities of investigators, ongoing training is needed to learn about problems with investigators and the sharing of knowledge of trial sites.

Accessibility to government information websites has aided in the knowledge of scientific misconduct. The Food and Drug Administration and the Office of Research integrity have posted on internet websites the names of investigators who have been disbarred/restricted and related public health service (PHS) administrative actions. Information can be accessed through the FDA Home Page: www.fda.gov/ora/compliance.ref/ default.htm

Investigator, IRB, sponsor warning and NIDPOE letters are accessible on the FDA website as well.

Was this article helpful?

0 0

Post a comment