CLINICAL TRIAL DISCLOSURE AND

RESULTS REPORTINGMarc Wilenzick, Esq.

Pharma

Regulatory & Compliance Conference

Washington, DC (November 2012)

Clinicaltrials.gov

Clinicaltrials.gov

Pfizer (as of November 2, 2012)

✘

Studies Registered on ClinicalTrials.gov

= 2,629

✘ Basic Results, Submitted to NIH for Posting = 529

Clinicaltrials.gov

Opportunities for Enhancing Transparency

Whether NIH Should Require Results Be Submitted In the case of Registered Trials for which an NDA is never Submitted or Not Approved

“The posting of summary results of trials where development (of the product or mechanism) has been abandoned would be reasonable.

Pfizer also would support a mechanism where the Secretary of Health and Human Services could require the submission of summary results of a specific trial, or of trials using a specific technology, where the Secretary determines that the data is important to patient protection (with respect to the design of other trials) or public health.”

Whether Narrative Summaries would be misleading or promotional?

“Summaries of clinical trial results could be prepared by the NIH, by the sponsor of the trial, or by a third-party

working for the sponsor or the NIH.

There is no reason that such results cannot be provided in a truthful and non-misleading fashion…

we [do] believe that the NIH should encourage the submission of truthful study results, in patient-

friendly language, and we welcome the development of guidance on the content, structure, and on procedures for quality assurance.”

What nontechnical language should be required to assist patients?

“We recommend that the NIH …

allow sponsors to voluntarily

report clinical trial results to NIH, in a consistent manner, for posting. A good framework …might be in a frequently asked questions

(FAQ)…:

•

What drug or treatment was studied? •

How many patients were involved?•

What kind of trial was this? •

What were the results of the trial?•

Have the results been confirmed by other studies•

What side-effects were observed? •

Where can I find more info about the trial•

Where can I find more info about the treatment?•

What questions should I discuss with my physician?”

Whether to require submission of the protocol?

“Pfizer and other sponsors already make protocols and pre-specified data analysis plans available to journal editors and regulators

--

the constituencies who are likely to be interested in reviewing such information.

If NIH were to require submission of the full protocol, it is important that NIH provide an opportunity to upload this information as a .pdf

file

(i.e., NIH should not require manual data re-entry).”

CISCRP Pilot●

Even though the vast majority of participants in clinical trials

want to know the results of the trial, these communications are uncommon

and there is no set paradigm (i.e. who should do this, when, how, and so on).

●

Pfizer sponsored a pilot with CISCRP to look at whether patients

would value being provided with a summary of the study results, in non-technical language (at the 6th

grade reading level).

●

Lyrica®

Test: Ongoing post-trial communication from volunteers’

last site visit until trial results become available; implemented and evaluated in Pfizer’s phase III Lyrica®

(pregabalin) Study NCT01057693 (trial start date of March 2010 and completion date of June 2012)

●

Toviaz®

Test: Lay language summaries of the results of a trial involving phase III Toviaz®

(fesoterodine) Study NCT00611026 (trial completed October 2009)

Lyrica

Trial: Communications

•

75 U.S. Sites asked to distribute mailings (thank you card at last visit and 2 update cards). A joint letter from Pfizer-CISCRP asked that they send this information to the study volunteers who completed, discontinued or left the study for other reasons. IRB approved Thank You Card.

•

30 sites sent out 95 Thank You’s; 44 sites sent out 167 first Updates; 43 sites sent out 153 second Updates.

•

Survey distributed to 189 study participants through 34 investigative sites in pre-addressed and stamped envelopes for return to CISCRP; confidentiality assured; 30 responses (16% response rate) from 10 states. Focus groups/interviews captured qualitative feedback from 17 study participants.

•

Interviews of 4 Principal Investigators, 1 Site Manager, 5 Study

Coordinators

10

Thank You Card10

First Update Card1

1

Second Update Card12

Toviaz

Lay Summary Communication:

•

CISCRP translated technical summaries from ClinicalStudyResults.org

and ClinicalTrials.gov; conferred

with Pfizer on scientific accuracy. Print, audio, & webpage formats (6th-8th

grade reading level) assessed.•

Materials distributed to 78 Sites for mailing to 598 study participants; sites only needed to add patient address labels

•

54 sites mailed 459 packets•

Pre/post test Survey of subjects’

comprehension and

receptivity; 10-question post-test mailed with printed trial results sent to 459 study volunteers; 23% response.

•

Interviews with 12 Study Coordinators, PIs, and Site Staff as to time required, interest, concerns.14

CISCRP Pilot

Conclusion

“The overwhelming majority of study volunteers want to receive information on the results of their participation in clinical trials, yet most study volunteers never do. The strong and positive results of this in-

depth study indicate that the process of communicating clinical trial results following study completion is feasible and is supported by investigative site personnel.”

Expert Rev. Clin. Pharmacol. 5(2), 149–156 (2012)

Looking forward“Within 5 years, pharmaceutical and biotechnology companies will be routinely providing clinical trial results to study volunteers around the world in response to regulatory mandate (e.g., the Declaration of Helsinki and the Food and Drug Administration Amendments Act), public pressure and the necessity to build stronger relationships with patients who participate in clinical research.

The authors anticipate that the duration between study completion and communication of clinical trial results will be shortened from the current 12-month time frame, in part due to the growing impact of data management technology solutions and patient preference for timely information.”

Expert Rev. Clin. Pharmacol. 5(2), 149–156 (2012)

Questions and Discussion

A growing number of sponsor companies have expressed interest in providing lay summaries of their clinical trial results to their study volunteers. At this time, CISCRP is assisting a dozen companies in support of their post-trial communication initiatives.

Open Questions from Sponsors:•

What is your view on the sponsor's role in preparing clinical trial results

summaries in lay language?• What concerns do you have about the process we’ve tested?•

What are advantages you see with a process handled by an independent

nonprofit dedicated to this effort?• Is there a different process needed for pre-approval versus marketed drugs?• What are your comments regarding upcoming rulemaking?