Nwx-Os-Ophs-Owh-Rg01 (Us)

NWX-OS-OPHS-OWH-RG01 (US)

Moderator: Elizabeth Carr

1-05-16/2:00 pm CT

Confirmation # 6473619

Page 1

NWX-OS-OPHS-OWH-RG01 (US)

Moderator: Elizabeth Carr

January 5, 2016

2:00 pm CT

Coordinator:Welcome and thank you for standing by.At this time all lines will be on listen-only mode.During the question and answer session, please press star followed by the 1.Today’s conference is being recorded.If you have any objections, you may disconnect at this time.I would now like to turn the call over to (Rick Haverkate).You may begin.

(Rick Haverkate):Thank you very much (Robin).Good afternoon everyone and thank you for joining us for today’s consultation call on the notice of proposed rulemaking to revise, modernize, strengthen and make more effective the federal policy for the protection of human subjects that was promulgated as a common rule in 1991.

My name is (Rick Haverkate) and I’m the American Indian and Alaska Native Health Policy Lead at the Office of Minority Health at HHS and I’ll serve as the facilitator for this consultation call.The call is estimated to take about 90 minutes total today.Our - before we get started, I just wanted to remind everyone that this is a consultation call and that all comments will be recorded, transcribed and submitted as part of the public record.

We’ll begin the call with a brief overview of the notice of proposed rulemaking by Dr. (Jerry Menikof) who is the director for the Office for Human Research Protections, a component of the Office of Public Health and Science and the Office of the Secretary at HHS.His office is responsible for protecting the rights, welfare and wellbeing of subjects involved in research conducted or supported by HHS and helps insure that such research is carried out in accordance with the regulations described in the code of federal regulations, title 45, part 46.

We will open up the call for questions and answers and comments immediately following the presentation.Dr. (Menikof) says that his presentation will be about 30 minutes long.So with that, I will turn the call over to Dr. (Menikof) to provide his overview.

Dr. (Jerry Menikof): Thank you (Rick) and I’d like to thank everybody for your interest in this topic and we look forward to questions after I complete the summary.So this is going to be about the notice of proposed rulemaking and let’s get started.

So what I’m going to do is give some background, discuss the goals of the notice of proposed rulemaking which is often referred to as an NPRM and most of my presentation will be about a summary of the major changes that are being proposed.So first question, why is there a proposal to revise the common rule?And the common rules are the set of federal regulations relating - the main set of federal regulations that relate to protecting UN research subjects.

And the proposal is out there because the way we do research has changed in a variety of ways over past decades.If you go back 30, 40 years ago, many studies we primarily at a particular center, at a particular institution.Now we have many studies that are across many different sites - perhaps across the world.Our ability to do research has changed in a variety of ways due to better computing facilities, due to better algorithms, due to the existence of the net.We can collect vast amounts of data and we can process that data in a variety of ways.

We have the ability to collect massive amounts of genomic information.All of these changes mean it’s a different research environment than it used to be and so the goal is let’s make sure our rules are appropriate for the current research environment.

The goal is to attempt to better protect human subjects who are involved in research but at the same time another goal is to attempt to reduce the burden, delay and ambiguity for investigators to enable us to do the important research we all want to take place.

This slide gives an overview of the rulemaking process.It started back in July of 2011 with an advanced notice of proposed rulemaking and that was put out for public comment.Now we’re in the middle where we now have a notice of proposed rulemaking and that’s a document that actually proposes specific new change - new language for the regulations.This document was issued in September of 2015 and public comment- we’re currently in the public comment period which ends tomorrow and the goal is a final rule which at the moment is unclear exactly when that would occur.So that’s an overview.

The common rule is called the common rule precisely because a variety of entities within the federal government are bound by it and this slide indicates the 18 departments and agencies that currently are bound by it and as part of the current process one more agency will join in - the Department of Labor.

So going back to the goals of this endeavor - two goals or two broad goals.One is that to the extent we can do a better job in terms of protecting human subjects who are involved in research; let’s make changes that accomplish that goal.And secondly there’s been a lot of discussion of a variety of ways in which the current rules aren't actually in some ways may not be doing very much in terms of adding protections for research subjects but they might nonetheless be creating administrative burdens that are delaying or hindering important types of research.So to the extent that’s happening, let’s simplify the current oversight system and reduce those burdens.

Now I’m going to go onto a summary of the major changes that are proposed in the rule and that’ll be most of the rest of what I talk about.And there are eight major changes and they’re covered in this slide and the next slide.I’m going to very briefly go through the descriptions of them because the rest of my talk will be giving you more information about each of them.

So number one is improving informed consent.Number two is about almost always requiring informed consent for secondary use of bio-specimens in particular regardless of whether they’re identifiable in the hands of the researcher.Number three is mandating single IRB review of multisite research conducted at US institutions.Number four is eliminating continuing review for certain minimal risk research.

Number five is extending the scope of the rules to cover clinical trials regardless of the source of funding, meaning even if it’s not funded by a federal agency.Number six is to require certain privacy safeguards.Number seven is to exclude certain activities from coverage and number eight is to expand the categories of research that are exempt from the rules to accomplish the goal of better calibrating the level of review to the level of risk.Now let’s go on and discuss each of those in more detail.

So the first major change involves improving informed consent and here we’re talking about in general in any research study what can we do to get better informed consent and there is a section 116 in the current regulations in the common rule that introduces the topic of informed consent and it provides a variety of rules but we’re now proposing to change that in a variety of ways and one of the major changes is to emphasize the need to provide the essential information - the most important information that a reasonable person would want to know in terms of making a decision about whether or not they want to participate in a particular research study.

And the goal is to provide that information up front so that the person is given that most important information and that it’s not buried in for example a long form - a consent form that might be 20 or 30 pages and it - the most important information may be in the middle of page 15 for example.So and the way that will happen will be by creating a core part of the consent form with this most important information with appendixes which will have the less important information.

So again as this slide indicates, the information will need to be provided in sufficient detail but also has to be organized and presented in a way that facilitates the prospective subject’s understanding of the reasons why a person might or might not want to participate in the research study.So again the theme here is to remediate the concern of some people that consent forms these days are too often almost, you know, lawyer created documents designed to protect the institution as opposed to primarily achieve the goal of letting the prospective subject get the information they need to make an appropriate informed decision about whether to participate.

A related proposed change relates to posting the consent forms for clinical trials and in particular the proposal is that for a clinical trial within 60 days after the trial is closed to recruitment of subjects, a copy of final consent form has to be posted on a government website and notice here it is not saying that anything has to be posted during the time when people are actually being recruited.So the goal is sort of to create transparency and that by people knowing at one point or another a copy of a consent form will be posted somewhere and will be made public.People will do a better job from the outset in terms of producing a good consent form.

You should note this is a onetime requirement so you do not have to keep changing the consent for nor do you need to post a consent form for each site in the clinical trial.All you need is one version of it for the entire clinical trial, even if it’s multisite.Now let’s go onto the second major change and this relates to secondary research with bio-specimens and in particular with the identified bio-specimens.

And what the proposed change will require is that consent will almost always be needed if you’re conducting research with a bio-specimen and here we’re in particular talking about secondary research with bio-specimens so an example - imagine that you kind of went to the doctor for medical care and they drew some blood and they didn’t need all of the blood so some of it was left over after they did your clinical test.

And so under the current rules if that bio-specimen is given to a researcher and the researcher is not told who you are - they’re not given your name or your medical record number or any other information that would make it easy for you to be identified by the researcher then under the current rules you’re not considered to be using a human subject and therefore no consent is needed.

Under new rules you would be considered to be using a human subject and again in general you will need some form of consent and as a formal matter this change will be accomplished by expanding the definition of what constitutes a human subject.

And there will be one type of exclusion from this requirement and in particular this exclusion relates to research that is designed to generate information that is already known about a person.So if you’re doing that kind of research then you wouldn’t have to meet this new consent requirement.And an example of that is imagine that you’re doing some new in vitro test to detect a particular genetic mutation and you want to test it on for example the blood of some people who you know are positive that already have the mutation and on the blood of some people who you know do not have the mutation.

And again so by using the blood of these people, you’re not actually generating any new information about them.All you’re doing is trying to determine whether or not your test is accomplishing what it wanted to do.So if you met those standards, you would not need to obtain informed consent.

Now let me tell you something about the way in which informed consent can be obtained for meeting this new requirement and under the rules currently in most cases when you get somebody’s consent, you get consent for a specific research study.In contrast the new consent requirement relating to this type of bio-specimen research will allow the use of a new broad consent template or form which the federal government will draft and release.

And what - when somebody signs - well when somebody reads this consent form and if they agree to sign it, what they’ll be agreeing to is the storage of the bio-specimen and the use of the bio-specimen for unspecified future research in contrast with consent for a specific study and basically the storage and use of the bio-specimen would be made exempt from the regulations if the form is used.

And I should point out there are some time limitations in certain circumstances relating to the period of time during which this consent would be valid - in particular there’s a ten year period relating to newly collected bio-specimens and using them for research.

Okay so now let me move onto a related issue which is the circumstances under which an institutional review board or IRB would be able to waive the consent requirements.Currently there are rules in the common rule that allow the waiver of consent in certain circumstances and given the new consent requirement for this research with bio-specimens, those waiver rules will be timed relating to the research with bio-specimens and the goal here is to basically in most instances require consent.

So in particular the first two bullets in this slide are giving the new requirements that an IRB rule of health have defined and have been met before an IRB can waive consent.So there would have to be compelling scientific reasons for the use of the bio-specimens and the research could not be conducted with other bio-specimens for which informed consent was or could’ve been obtained.

And the third point and the third bullet here is that if in fact a person was asked to provide broad consent and they declined to do that then an IRB would no longer be able to waive consent even if the two earlier conditions on this slide were met.So bottom line goal is that the waiver is intended to be rare.

So let me now change from talking about bio-specimens and talk about a related type of research which is secondary research with data.By secondary research, we’re talking about research with data which comes into existence for some other purpose other than through this specific research study that the researcher is trying to conduct and what I want to note is a number of things that are not changing with regard to the rules relating to data.So for example there’s not going to be a change to the definition of what constitutes identifiable private information.

That definition is now going to be expanded and I’ll just note that the ANPRM back in 2011 did have a proposal to change that standard and in particular used the HIPAA rules and that is no longer being proposed here.

So the core rules relating to secondary research would de-identify data unchanged so if you’re continuing to do research, would de-identify data.You will not be using a human subject which is consistent with what the current rules are.

Furthermore the rules I described to you relating to research with bio-specimens do not alter rules relating to secondary research with data even if the data we’re talking about has been obtained from a bio-specimen or even if it was obtained in some other way.Bottom line all data regardless of the source - whether it came from a bio-specimen or some other source - is going to be treated the same way.

Furthermore in a variety of ways the proposals in the NPRM actually increase the ability to conduct research with identified data without consent and this is as soon as appropriate protections are in place and the rules actually require a variety of new protection.

So for example, while the new consent forms I talked about can be used not only for bio-specimen consent but for consent for research with identifiable data.On the data side this is merely an option.Unlike for bio-specimens there are many other options a data research will have apart from using the broad consent or obtaining broad consent and this slide gives you some of those options.So for example a researcher could use data that is stripped of identifiers.

There could be a one way link to the identifiers - one way meaning that the decoded link is not to be released to the researcher.There can be an IRB waiver allowing the use of the identifiers and there will be in fact a new exemption allowing use of identifiable data with notice instead of consent and just note that any one of these might be preferable to obtaining broad consent on the data side.

You should contrast this to the fewer options a researcher will have doing research with bio-specimens whereas I noted it will be rare that they could do that without consent.Okay so that covers the consent issues relating to bio-specimens.

Now let’s move onto major change number three and this relates to single IRB of multisite research and basically what this will require is that there will be single IRB review - review by sort of one single central IRB from multisite research conducted in US institutions unless - and the two bolts here give the exceptions to this.