Yesterday I had the privilege to chair the Clinical Trials Disclosure and Transparency Summit.
Here are my opening remarks:
Simplistic solutions to important public health issues are generally wrong, often deleterious to the issue at hand --and often hide political versus public health agendas. Or as Henry Kissinger once said:
”The real distinction is between those who adapt their purposes to reality and those who seek to mold reality in the light of their purposes.”
And so, with that introduction, welcome to the Clinical Trial Disclosure and Transparency Summit.
In a recent op-ed in the New York Times, biasedly titled, Health Care’s Trick Coin, Ben Goldacre (the author of the neutrally titled book, Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients, made a number of serious allegations – and factual mistakes in his discussion of clinical trial transparency – specifically that the Clinicaltrials.gov registration requirement in FDAAA isn't being implemented and that only “full transparency and publication of clinical trial will address the issue.” It’s not so simple – and the facts matter.
As the former senior government official in charge of clinicaltrials.gov, it’s important to look at the facts – and the numbers.
In 2000, the National Institutes of Health (NIH) launched ClinicalTrials.gov to provide public access to information on clinical studies. Although it initially contained information primarily on NIH-funded research, it has been expanded to include both publicly and privately supported clinical research.
Since the launch of the site, it has been enhanced to significantly increase data sharing. The ClinicalTrials.gov database includes information on nearly 140,000 clinical trials in all 50 states and 182 countries.
Is anyone accessing this wealth of information? Yes! The NIH reported last year that ClinicalTrials.gov “receives more than 95 million page views per month and 60,000 unique visitors daily.
Facts do not cease to exist because they are ignored. Mr. Goldacre should realize that reality, although sometimes inconvenient to ones argument, remains reality.
As we progress through the next two days, here are some issues we will consider:
· The FDA is at the nexus of vast amounts of patient-level clinical data – what role will transparency play in making such information available? How might the agency accomplish such a task, how would it be funded – and where does such an initiative fall on the agency’s long list of urgent priorities?
· How will current AbbVie/Intermune legal decision in the EU impact transparency issues here at home?
· How will the IOM report impact how we view transparency going forward? Indeed – how will the IOM move forward on this issue – or will it?
· Should transparency be a government dictate or a working collaboration between interested parties both private and public – and what role should patients play. Should there be formalized transparency consortia? Should it be global?
· What are the implications for intellectual property and the connected question of incentivizing (or dis-incentivizing) investment in innovation? Is transparency a Trojan horse to attack patents and intellectual property rights?
· How can we avoid making transparency a game of “gotcha” such as what happened at the 2010 Avandia hearing where a grandstanding Henry Waxman pointed his finger at the GSK research chief and stridently said, “do you swear under oath that you will make all clinical trial data available? Only to get the embarrassing response, “Congressman, it’s available right now at www.gsk.com.”
· What about the availability of data from unpublished negative trials? Why aren’t payers asking for these before they make reimbursement decisions? For those of you following the debate over FDAMA 114 and the use of pharmaco-economic data for reimbursement decisions, this shouldn’t be an unfamiliar discussion. Can a free-market solutions drive transparency?
· Can transparency become a competitive advantage as well as a public health imperative?
After all, good things happen when everybody wins.
Ladies and Gentlemen – start your engines.
The Summit’s first speaker was Dr. Richard Moscicki, CDER’s new Deputy Director for Science Operations. His presentation focused on the transparency dichotomy of “the promise versus fear and loathing.”
As to “why” transparency, he offered reproducibility, re-analysis the potential to identify new information (placebo effects, biomarkers, endpoints, trial designs).
And then his talk got interesting. He laid it on the table that one group that is silently against transparency is academics – because they don’t want to be cornered into making studies public if it impacts their ability to publish.
The FDA’s impediments to data sharing, according to Moscicki are (1) Legal (data ownership, HIPAA/privacy, proprietary information), (2) technical/practical (format, data standards, CDISC, redaction), (3) Resources and, (4) the agency’s need to focus on its key mission.
Per that last point, he honestly shared that the FDA does not view (at least at as of right now) the issue of clinical trial data transparency as a key agency agenda item – unless there was move to move it to the head of the regulatory queue via user fees. (That would be DTUFA – Data Transparency User Fee Act. Folks – you heard it here first.)
But transparency is important and, per Moscicki, “inevitable” – and to that end he discussed the agency’s recent Federal Register Notice (Masked and De-identified Non-Summary Safety and Efficacy Data).
FDA invites comments on the issues it should consider with respect to the availability of clinical and pre-clinical study data after steps have been taken to “de-identify” it by removing any personally identifiable information and “mask” it by removing data that could link it to a specific application or sponsor. Specifically, the agency is interested in comments from the public on the following topics:
– What factors should be considered in masking study data (e.g. should certain data fields be removed or modified; number of different products to pool within a class)?
– Should there be any limitations on the agency’s ability to make masked data available?
– In addition to current FDA requirements to remove any names and other information that might identify patients, what other information should FDA consider when de-identifying the data?
– Would regulatory changes facilitate the implementation of this proposal?
– In what situations would disclosing masked data be most useful to advance public health?
Moscicki stressed that FDA’s approach has been under development for several years and
* It is not linked to EMA proposal;
* FDA is not contemplating routine preparation and release of de-identified and masked clinical and non-clinical study data;
* The agency is encouraging independently organized efforts to create, curate and share clinical trial datasets from all sources.
Dr. Moscicki’s complete PowerPoint presentation can be found here.
Next up on the agenda was Sir Alasdair Breckenridge, former Chairman of the MHRA and currently the Chair of United Kingdom’s Department of Health Emerging Science and Bioethics Advisory Committee.
Sir A. challenged the assemblage with the statement that transparency is “a process without a beginning or an end. It is a continuum.” And, “Transparency is like feeding a hungry dog – you more you give it, the more it wants.”
Cry havoc – and let slip the dogs of data transparency.
His presentation focused on four key questions:
(1) Should the public have access to data on which regulatory decisions are taken?
(2) What are the advantages and disadvantages of increased transparency?
(3) What are the key distinctions between transparency and communication (specifically the issue of public health literacy and numeracy – and the “road testing” of released information)?
(4) Will increased transparency lead to increased trust in regulators and industry?
On that last point, Dr. Breckenridge pointed out at increased transparency does not lead to increased trust. Trust depends on perceptions of honesty and competence, and transparency may expose inherent inefficiencies in a system. And that’s a good thing – if we really mean to make the most of transparency.
Transparency cannot be “for thee but not for me.”
He offered five keystones for moving forward:
(1) Agreement on timing of release of information
(2) Agreement on nature of information to be released
(3) Standards of protection of personalized data
(4) Standards for meta-analyses
(5) Rules of engagement for observational studies
He also discussed the EMA’s mad dash towards data transparency and the severe blow it was dealt by the legal victory of AbbVie and Intermune. A lesson that should be noted by the Ben Goldacres's of the world -- and the British Medical Journal.
Sir Alasdair’s PowerPoint presentation can be found here.
Maybe the FDA’s incremental and collaborative approach is best after all. Slow and steady ain’t sexy – but it generally works best -- and is in the best interest of the public health.
