In the ever-evolving landscape of clinical trials disclosure, navigating the intricacies of registration, compliance, and ethical transparency has become more crucial than ever. Pharmaceutical and medical device companies must not only adhere to regulatory guidelines, but they must also balance this against the growing need to ensure transparency and protect sensitive information.
In this blog post, our clinical trial experts share insights on some of the most frequently asked questions in the clinical trials disclosure space including topics such as public registration of clinical trials, mandatory compliance fields, timely disclosure of trial results, and the ethical considerations of data sharing.
Does my Study Need to be Registered on a Public Registry?
This is often one of our most asked questions. If you are planning to conduct a clinical trial (for either a drug, biologic, or medical device), knowing and understanding which trials are required by law to be registered on a public registry (and to which registry) and which ones are voluntary is crucial. Especially if you want to avoid potential monetary fines.
The public registry in the United States is ClinicalTrials.gov, which defines this as an 'Applicable Clinical Trial' or ACT. An ACT is a clinical trial that studies a drug, biologic, or device product and meets all the following criteria:
- Is a clinical investigation (interventional; i.e., if the study is a pediatric postmarket surveillance of a device product as required under Section 522 of the Federal Food, Drug, and Cosmetic [FD&C] Act)
- Is a controlled clinical investigation
- Is other than a Phase 1 study (or a device feasibility study)
- Investigates a drug (or biologic) subject to Section 505 of the Federal Food, Drug, and Cosmetic (FD&C) Act or Section 351 of the Public Health Service Act or an FDA regulated Device Product
- Either: conducted at a site in the United States, study is conducted under a US Investigational New Drug (IND)/Investigational Device Exemption (IDE) Number, or is manufactured in and exported from the United States
If you are still not sure if your trial meets the definition of an ACT, the NIH has developed a checklist that can be leveraged. Once you have determined if you will register your clinical trial (whether per the requirement or voluntarily), you are then obligated to follow the legislation/guidelines that dictate what information must be presented and how often it needs to be updated.
My Study is Not an ACT, Do I Still Need to Post?
There could be several drivers behind public registration of a clinical trial, such as corporate transparency policies or regulatory authority commitments. Another compelling reason would be the desire to publish clinical trial results in a journal. Even if a clinical trial is not considered an ACT by definition, the International Committee of Medical Journal Editors (ICMJE) Guidelines recommend that medical journal editors require the registration of clinical trials in a public trial registry (any WHO International Clinical Trials Registry Platform [ICTRP] is acceptable) at or before the time of first patient enrollment. The ICMJE will use the date the trial registration materials were first submitted to the registry as the date of registration and registrations posted retrospectively will not qualify. In addition, not only is registration required, but ICMJE also requires that the Sponsor's include their data sharing plan in the registration.
Thus, it could be helpful to include the potential publishing of study results in the decision tree when considering whether or not to register a clinical trial.
Once I Have Registered my Study on ClinicalTrials.gov, is There Anything Else I Need to Do?
Yes! There are 14 fields on the ClinicalTrials.gov public registry that have ongoing compliance requirements, which means that those fields must be updated within 15 or 30 calendar days of the change occurring (not when you become aware of the change). In addition, protocol amendments that impact any information on the registry must be incorporated within 30 calendar days.
Registry fields with mandatory compliance include:
- Study start/end date (primary and study completion dates)
- Intervention name (after establishment of a non-proprietary name)
- Availability of expanded access/Expanded Access Record
- Overall Recruitment status
- Individual site status (after a change in status for any individual site)
- Human Subjects Protection Review Board Status (for any status change)
- Sponsor Contact Information
Once the clinical trial has been successfully registered, it is best practice to set up a monthly review cycle to identify any changes in the above fields to ensure continued compliance throughout the clinical conduct of the study.
When are my Clinical Trial Results Due on ClinicalTrials.gov?
For ACTs, results for all identified primary and secondary endpoints must be disclosed on ClinicalTrials.gov within 1 year of the primary completion date (last patient, last visit for the specified outcomes). Identified means anything labeled in the clinical trial protocol or statistical analysis plan as a primary or secondary endpoint; exploratory endpoints or endpoints labeled as other are not required to be disclosed.
An important thing to keep in mind is that regardless of clinical trial outcome and/or overall study completion (terminated, completed), if the data were collected, legislation (FDAAA Section 801) requires that the data are reported. So even if a study is terminated, if data were collected (whether there is a plan to analyze the data or not), the NIH has NOT in the past (in our experience) accepted that data 'were not analyzed'. The only acceptable reason (to the NIH) for not reporting results is if NO data were collected.
Is it Required to Upload Documents at the Time of Posting Results on ClinicalTrials.gov?
Yes, Sponsors are now required to upload a final version of the clinical trial protocol and/or statistical analysis plan with their results on ClinicalTrials.gov for ACTs. Even for voluntary studies, if the decision is made to post the results of the clinical trial, then all applicable legislation/guidelines must be followed, including posting of these files.
This needs to be the FULL version of the protocol, not a synopsis, which can bring up not only personal, but also commercial data privacy concerns, so consideration may need to be made for masking or redacting information in the documents (including building this into your timeline and review). Another question we hear often is, what information and how much should be redacted? Clinical trial Sponsors must balance the need to meet global legislative requirements and the need to protect not only personally protected data (PPD), but also company confidential information (CCI). In addition, if the protocol will be made public via multiple channels (EMA, Health Canada), you will want to ensure consistency in redactions across platforms. There are multiple guidelines and tools for Sponsors to use as they navigate the redaction of both PPD and CCI information in documents depending on the regulatory purpose.
What is the "Good Pharma Scorecard"?
The Good Pharma Scorecard (Bioethics International) uses multiple factors, including transparency and data sharing practices to rank companies on their bioethics and social responsibility performance.
For transparency and data sharing, they look at what companies are obligated (by law) to report on and if they completed those activities on time, specifically:
- Are trials registered within a reasonable timeframe (i.e., within 21 days of the start date)?
- Are results reported in a public registry or published in an indexed journal within a reasonable timeframe?
- Were the results reported within 30 days of initial FDA approval or 1 year after primary completion date (per FDAAA requirement)?
They also look at the following with respect to a company's data sharing policies:
- Does your organization have a public policy committing to sharing analysis-ready datasets and clinical study reports?
- Does the policy explain how those data can be requested?
- Does the policy commit to making data available by 6 months after approval by the FDA or EMA or 18 months after a trial completes?
- Does your company report the number of data requests received and how each one was handled (granted or denied)?
- The overall proportion of trials registered in a public registry where 'data sharing' is applicable
This is just one area that contributes to the overall score. How would your company rate on the above? You can check out this Good Pharma Scorecard to see if your company is on the scorecard and where they rank.
Conclusion
Conducting clinical trials means navigating a myriad of legislative requirements across potentially multiple countries, to first understand and then to comply. In today's highly regulated and ethically driven landscape of clinical trials, staying informed with clinical trials disclosure guidelines and requirements is paramount.
Planning for all the potential and future disclosures and transparency needs can be daunting. Do you need help deciphering the regulations? Not sure if you need to report the results of your clinical trial or how to do it? Have questions about what should or should not be disclosed? ProPharma can help you navigate the ever-evolving regulatory landscape, not only in the United States, but globally, with a flexible and agile team of trusted clinical trials disclosure experts.
Connect with us today to see how ProPharma's subject matter experts can help you with all your transparency and data sharing obligations.
