The simplification of the US Food and Drug Administration’s (FDA) compassionate use process (announced last February and expected to be finalized very soon) may not actually be all that much of a simplification in terms of the amount of time it takes a physician to fill out the form, an FDA official told Focus on Tuesday.
Richard Klein, director of the Patient Liaison Program in FDA’s Office of Health and Constituent Affairs, explained to Focus, following Monday’s article on the finalization of a new form and plans for an expanded access navigator, that “it has never taken 100 hours, or anything near it, for a physician to apply for expanded access for a patient.
“This is a distortion, much promoted by the Goldwater Institute, based upon the Paperwork Reduction Act estimate at the bottom of the form. The Paperwork Reduction Act requires an estimate of any information burden placed on the public by the federal government to be reviewed by the Office of Management and Budget, and charged against an agencies information collection budget,” Klein explained.
“Informally speaking to physicians who file the 1571 [the previous compassionate use form] suggest to me that the time to complete the request generally takes them less than an hour,” he told us.
The 100 hours estimate, which was cited by Peter Lurie MD, MPH, associate FDA commissioner for public health strategy and analysis, in a blog post last year on the simplified process, is actually based upon the maximum estimated time required to pull together and document all of the information necessary for a commercial sponsor to file an original IND, Klein said.
“I’ve never agreed with including the 100 hours figure in the blog post. Again, the sentence, if read carefully, points to the 100 hours ‘listed on the previous form.’ The reference was to the Paperwork Reduction Act estimate required on all federal forms, rather than to the time it actually takes to complete the form for expanded access requests. I don’t see how readers could be expected to readily recognize that distinction,” Klein said, adding, “I think the juxtaposition to the 100 hour estimate might suggest a more dramatic reduction in time necessary to complete the new form, but it perpetuates the myth, or meme, that the estimate applies to the treatment use application.”
“I am trying hard to set this record straight, since the underlying premise of the 100 hour myth is not based in fact,” Klein added.
As Klein noted, the 1572 form, which is the form used to make compassionate use submissions, has a number of other, different uses too, such as for the submission of adverse event reports, or protocol amendments to an existing IND.
“These manifold uses all require considerably less time to complete than the original, but the estimate is based upon the most complex use of the form for original submissions of information to support human exposure to a new drug product,” Klein said. “A good bit of information, such as chemical make-up, manufacturing processes, quality control, toxicology data from animal studies, etc., are necessary to minimize risks posed to potential research subjects… Because that is the primary use of the form, the time estimate is based upon the maximum estimated time required to pull together and document this information for submission.”
Although the same FDA form is used to request expanded access or compassionate use, only select and limited fields need be filled in for such cases, Klein explained, as “the bulk of the information is already available in the commercial sponsor’s IND. This is the purpose of the Letter of Authorization, which permits FDA to cross-reference the information contained in the commercial IND.”
FDA’s switch to a new form, known as Form 3926, which is expected to be finalized soon, “is actually a distillation of the information required on the 1571 specific to single patient expanded access requests,” Klein said. “Our goal was to pull the appropriate fields out of the more complex and confusing form to make it easier and more straightforward for physicians unfamiliar with the regulatory paperwork to submit a treatment use application.”
Use of New Form
As to why the new form has taken more than a year to finalize, Klein explained that creating any new form “in the federal government is a complex process. More so than most people would realize. (Certainly more than I had realized!)”
The form needs to flow through logistical processes, such as through the FDA mailroom, which would need to know exactly where in the agency, based on certain information on the form, to route a form submitted by mail, he told us. “So everyone potentially involved anywhere in the process needs to be involved. There are different routes through which an application may be submitted, and different destinations depending on the appropriate review divisions to which it needs to be directed depending on disease or condition.”
And until the form is finalized, FDA cannot request the use of the form.
However, Klein noted that since the form has been posted in its draft form, “a small number of physicians have submitted the form to request individual patient treatment access to an investigational drug. In these cases, the agency has accepted the form in lieu of the 1571 as a way to expedite the application. As I mentioned, the information required by the two forms is basically the same. But the format is different (simpler and hopefully less confusing to fill out). “
He also noted that the new Form 3926 “has evolved and improved from its original draft form as a result of internal review and public comment, making it more useful for the entire process of submission and follow-up, which originally would have required reverting back to the 1571 for subsequent changes and addendums.”
Right to Try
Like a number of others, Klein said he is not aware of any cases of patients or physicians gaining access to investigational drugs in any state that has passed “Right to Try” legislation.
The legislation, which has passed in 28 states thanks to the campaigning of the Goldwater Institute, is meant to skirt around FDA’s compassionate use process and allow access to investigational drugs more quickly.
“I have to question what incentive a company might have to take that route, rather than an established national process that carries no legal ambiguities, and has quite a good track record,” Klein told us, citing statistics on expanded access INDs granted by CDER and CBER from 2009 through 2015. “I wonder, too, why access under Right to Try, which is supposed to afford patients a right to gain access to investigational therapies outside of clinical trials would operate under a shadow of secrecy."