Nick DeVito and Ben Goldacre

Background

The US FDA Amendments Act (FDAAA 2007) requires certain clinical trials to report their results onto ClinicalTrials.gov within one year of completion. Our FDAAA TrialsTracker shows all individual trials that breach this legal requirement. Once a week, we write about one unreported clinical trial: you can read more background here and read past entries here.

Trial NCT02461745

This week’s unreported trial is titled “A Phase IV, Multisite Study of the Treatment of Chronic Hepatitis C Virus Infection Genotype 1 in a Real World Large Health Maintenance Organization: An Evaluation of Real World Sustained Virological Response and Patient Reported Outcomes” (NCT02461745). This trial has an estimated enrollment of 200 hepatitis C patients. The study was not randomized and had no masking. The experimental intervention was ombitasvir, paritaprevir/r, and dasabuvir with the addition of ribavirin; the control group was ombitasvir, paritaprevir/r, and dasabuvir only. The primary outcome was sustained virological response (SVR) at 12 weeks. The secondary outcome was SVR at 4 weeks.

Clinical discussion

The WHO estimates that 71 million people worldwide have chronic hepatitis C infection causing ~400,000 deaths each year. There has been rapid advancement in the treatment of hepatitis C in recent years. New classes of antiviral therapies can, in some instances, completely cure the disease. This includes the combination therapy under study in this trial (known commercially as “Viekira Pak” in the US). With the price of these therapies exceeding $80,000 for a full course, it is important that real world studies assessing the impact of the drug are conducted. Pragmatic trials conducted by health services are relatively uncommon, so this study would be an outstanding example of highly clinically relevant research, had its results not been left unreported.

Legislative discussion

As a Phase 4 trial on an approved therapy, this study is unambiguously required to report results on ClinicalTrials.gov. The primary completion date was May 2017, meaning that results for the primary outcome should have been reported online by May 2018. You can read some general background about the FDA Amendments Act 2007—and why a trial is considered “due”—here and here.

We intend that this series should occasionally shed light on interesting issues around transparency rules, and how registry data is used. According to FDAAA 2007 and its final rule, sponsors have a responsibility to maintain their registry entries with complete and accurate data. Here we note that Kaiser have provided contradictory data. “Primary Completion Date” is defined by ClinicalTrials.gov as “the date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.” The “Study Completion Date” is defined as “the date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant’s last visit).” Currently this trial lists an actual primary completion date of May 2017 and a study completion date of July 2018. This is inconsistent with the listed outcomes as the primary outcome is reported at 12 months while the secondary outcome is listed as a 4 month outcome. As an aside, the sponsor has also failed to meet the FDAAA requirement for a specific date (only month and year are given).

The discrepancy in dates may be due to another issue with the trial entry. Both the title of the study and its description note that patient reported outcomes (PROs) will be collected. The included study description says that the study will collect data on “virological response rate, subject adherence, and subject reported outcomes”: yet the only outcomes listed for the trial are SVR at 4 and 12 weeks. If PROs are being collected, but have not been disclosed on the registry entry, then this may explain the additional time needed to complete the study. It is impossible to verify this possibility, with the information provided. The importance of prespecified outcomes for ensuring the integrity of reported results is detailed elsewhere.

Conclusion

This unreported trial was sponsored by Kaiser Permanente in California, USA in collaboration with AbbVie. The PI is Dr. Lisa M. Nyberg of Kaiser.  As of 9 July 2018, this trial is at least 39 days overdue to report. We hope the investigators will share the results of this unreported trial soon.

 

Ben Goldacre is a doctor, author, and director of the EBM DataLab at the University of Oxford. He co-founded the AllTrials campaign for trials transparency.

Competing interests: BG has received research funding from the Laura and John Arnold Foundation, the Wellcome Trust, the Oxford Biomedical Research Centre, the NHS National Institute for Health Research School of Primary Care Research, the Health Foundation, and the World Health Organization; he also receives personal income from speaking and writing for lay audiences on the misuse of science.

Nicholas J DeVito is a researcher at the EBM Datalab at the University of Oxford.

Competing interests: ND is employed on BG’s LJAF grant and is a Naji Foundation Scholar at the University of Oxford.