Secondary Research with Biological Samples and Data Under the Revised Common Rule
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Secondary Research with Biological Samples and Data Under the Revised Common Rule

Carol Weil: Hello, everyone. I’m Carol Weil at the National Cancer Institute. On behalf of our NCI ENRICH Forum team, I
would like to welcome you to today’s presentation with OHRP’s division of education and development
director Dr. Yvonne Lau. A few logistical comments for our remote viewers
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to the media viewer panel. You will be asked to enter your name. Before introducing Dr. Lau, I want to note
that the views expressed in her presentation are those of the speaker and not necessarily
of the NCI or the NIH. Our speaker today, Yvonne Lau, is no stranger
to the NIH, and we are delighted to welcome her back. Before joining OHRP in 2014, Dr. Lau served
as the extramural research integrity officer in the NIH office of extramural research. Dr. Lau is a consultant surgeon with the Hospital
Authority of Hong Kong and founded Hong Kong’s first multidisciplinary breast center and
breast cancer patient support group. In addition to her medical background, Dr.
Lau obtained her master in bioethics and health law and her PhD in bioethics from the University
of Otago in New Zealand. And with that, I will turn the floor over
to Dr. Lau. Yvonne Lau: So hello, everybody. And I’d like to thank Carol for my introduction. So let’s start today. There’s a lot of details I’d like to share
with you, so I’m just going to go ahead and move forward. So again, the views expressed do not necessarily
represent those of the Department of Health and Human Services, apart from, like Carol
just said, NIH. All right. So this is the overview for today’s presentation. I’m going to start by giving you a little
bit of a brief introduction on the transition provisions on the revised Common Rule, just
a few slides on that to put you in the moment. And then I’m going to talk a little bit, review
the key terminologies related to secondary research, which is the topic that we are talking
about today. I also want to show you some of the regulatory
flexibilities for secondary human subjects research with biospecimens and data. So the point of this is also to show our researchers
that it’s really — the regulations are really not a mountain to climb. And in fact, we built in a lot of regulatory
flexibility to facilitate this kind of research going forward. And in fact, as we move into this age of big
data and search data, people will actually start thinking whether these kind of flexibilities
provide adequate protection for human subjects. Nonetheless, it does actually help [inaudible]
research. Then I’m going to go and talk a little bit
about informed consent options for those type of research that are considered non-exemption
subject research. And finally, a bit of additional relevant
information as well related to this subject. So I hope that everybody is well aware by
now that there were revisions to the Common Rule and that these revisions, the compliance
date for these revisions were January 21st, 2019. So it’s almost ten months ago by now. So you should really know that we are in the
era of the revised Common Rule now. I do note that the revisions are only to the
Common Rule, which is the subpart A of 45 CFR 46. We generally would refer to the revision to
the Common Rule as the new rule, the revised Common Rule, but its official name, it’s the
2018 Requirements. 2018 because in effect they actually came
into effect in July of 2018, although the compliance of the majority of the rule was
actually not until the beginning of this year. Just a bit of background. So because we’re talking about secondary research
with biospecimens and data, I’d like to give you just a very brief overview of the key
changes made in this area. What’s previously under the rule considered
as not human subjects research, that continues to be the case, and there’s really no change
for now. What previously could be considered exempt
human subjects research, there has been expansion because of the expansion in the exemption. And then what’s previously considered non-exemption
subject research, there are some changes to the informed consent waiver requirements. And there is also a new thing called broad
consent option under the revised Common Rule. So here you are with a chart showing you the
red line is the compliance date, January 21st, 2019. What it really means is that any studies that
are started after this date, studies initiated on or before this date must comply with the
revised Common Rule. It’s pretty obvious. Except for the word initiated, you have a
definition at the bottom. It means that it’s first determined exempt
or initially proved by an IRB or granted a Secretarial Waiver. The studies that were initiated before this
date must continue to comply with the pre-2018 requirements, in other words, the old rule. And as they transition over this date, they
continue — ongoing studies continue to comply with the old requirements unless institutions
have made a determination to transition the studies to comply with the 2018 requirements. And I emphasize, it’s institutions that have
made a decision to transition, either one or a category or a whole group of studies. So it’s not the whimsical determination of
an investigator. So it needs to be the institution and IRB
needs to document this is taking place and upon what date. So now let’s move on and talk about some of
the key terminology. I’ve noticed it’s kind of confused people
to the utmost. Notice also that when I talk about these,
I’m really referring to how the regulations think about these terms, not the layperson. All right? So what is secondary research? This is the research use of informational
biospecimens originally collected for non-research purposes. Examples of these would be leftover blood,
samples from routine clinical tests, or general information collected. For example, we’re going to have the census
next year, so information is collected in the census. Or any other type of information that is collected
for purpose that serves an institution because of their functions, administrations, or whatnot. All right. So it’s not really collected for any research
purpose. Now, if you have a researcher going to Survey
Monkey or to a survey firm and that survey firm has been collecting a whole bunch of
information [inaudible] particular interest in the subtopic. That information that has been routinely collected
or been generally collected by that firm, and if the investigators want to get a hold
of some of that information for use, that’s secondary research. However, if the investigator started saying,
well, you know what, let’s collaborate and I have some research questions. Can you incorporate these into that survey. Then there’s collection especially for research,
and it takes it out of the secondary research situation. MS: So if there is CT images or other images
done for clinical care, would that come under that? Yvonne Lau: Yes. Yes. So the other type would be research use of
information of biospecimens originally collected for research studies other than the currently
proposed one. So here’s an example for you. So blood samples that were left over from
a study evaluating a new diabetes drug being used for a new study. It’s being proposed for use in a new study
on genetic predisposition of diabetic patients. The way to think about this is really to go
back to the original research protocol and look at it and see, well, the current research
and the research [inaudible] proposing, was there any specificity about this research
that was actually mentioned in that original research. If there’s none, then you’re talking about
something that is different from what was before. And so you can be in this situation [inaudible]. And then people would ask, well, you know,
I don’t really see this term in the set of regulations, but I’m going to convince you
that, in fact, the idea, the concept of secondary research is very closely related to the definition
of human subject, the regulation definition of human subject. Here is the definition here. Most of you are familiar with it. You might see that there are more words in
this new version, but it’s essentially the same concept that we have in the old rule. So here it says human subject is a living
individual about whom an investigator conducting research obtains information or biospecimens
through intervention or interaction, et cetera, et cetera. The words through intervention or interaction
are bolded here. I want to really focus on that. So in other words, you are actually for the
purpose of the current research, you’re interacting and intervening, intervening by getting blood
or something like that from that individual. That would make that particular research typical. It would be clinical trials, clinical studies. That would make that a human subject research,
right? So let’s think about secondary research. Secondary is when it’s not that, right? So in secondary research, there’s no interaction
or intervention with individuals specifically for the current research. So whatever information, materials, biospecimens
that your researcher is proposing to use for the purpose of this current research, they
were all collected through an interaction, intervention that happened elsewhere under
other circumstances. Right? Under other circumstances. So now we see the second part of the human
subject definition. This relates to when a secondary research
is also not human subject research, right? So the second part of human subject definition
says a living individual about whom an investigator conducting research obtains, uses, studies,
analyzes, or generates identifiable private information or identifiable biospecimens. So whenever you have something that is identifiable,
it will make it human subject research, right? So what do we have now as a scenario? Secondary research part 1 doesn’t apply plus
part 2 doesn’t apply, and that makes it secondary research that is not human subject. Okay. So you might be wondering, okay, well, then
what about the term identifiable. What does it mean under the Common Rule? I stress that this is the definition under
the Common Rule. It’s the same in the old and in the revised
version of it. So it says here identifiable private information
or identifiable biospecimens refers to private information of biospecimens for which the
identity of the subject is or may readily be ascertained by the investigator or associated
with the information or biospecimen. In other words, it’s kind of a fluid concept. It’s kind of subjective. You have to apply this standard. Whatever you have in your possession, can
an investigator, based on what they have now, readily link them back to living individuals? Right? So it’s a subjective standard. And every time, you have to kind of think
about it, think through it. Of course, the obvious other information would
be you look at the materials the investigator is using and you ask whether there are obvious
information, subject identity information that are linked, associated with that information
or biospecimen. MS: Just to clarify, this is the investigator
doing the secondary research, right? Yvonne Lau: This term identifiable definition
applies to all sorts of things. So whenever under the Common Rule we refer
to something that is identifiable, that is the definition that we go to. And those are the standards that we go through
when we think about them. All right. So I know that you see applications and you
find research is using these terms coded, identified, anonymized. We kind of know what they’re talking about,
but we also kind of really don’t know because in order to apply the Common Rule, you really
have to go through what we just talked about, the standard that we talked about. I cannot, for example, assume that coded means
that that’s what they mean, right? The coded means that they have [inaudible],
right? It could still be that they have the key to
the code and so they can readily link them back to living individuals. So you really have to think about how the
definition applies accordingly. Unfortunately for the purpose of the Common
Rule, we don’t have the simple to refer to list like we have for the HIPAA, what they
refer as the HIPAA identifiers. We don’t have such a list. In a way, it’s good because it builds in some
flexibility to how you think about identifiability. I also want to point out that the things that
we generally might consider unique identifiers to people, so for example, fingerprints. It’s uniquely identify a person. It’s unique to a person. That’s what it is. Unique to a person, right? If you have fingerprints and the individual’s
name, then you can uniquely identify them, but you need to have both, right? So if an investigator, let’s say they have
a set of fingerprints of a whole bunch of people and they just want to look at patterns
and they don’t want to have the information about who these fingerprints belong to. Then to us, that would be nonidentifying under
this Common Rule. I want to say that Common Rule agencies revisit
the meaning of the definition every four years. At the moment, I don’t have information on
that yet as to when this will begin. So this is just what I said already about
coded materials. So coded information is not enough. We need to know that investigators have not
interacted or intervened with subjects to collect the materials for the purpose of this
research and that the investigators cannot readily identify or link the materials back
to the individual. Same kind of equation. All right. So you have this flowchart of how we actually
think and apply the common rule. You start with the question research using
biospecimens or data, and you ask the first question. Is it human subjects research. And we go down the arrow and say, oh, no,
because it’s secondary research and it’s with nonidentifiable materials, so it’s not human
subject research. And for the purpose of the regulation, there’s
really no requirement for the formal IRB review and approval process. However, if your answer to this question is
it human subject research is yes, then you need to continue to ask further questions
as to whether then the Common Rule applies to that research. So now we’ve — MS: Can we go back one slide? One more. The key word here is readily identifiable. Who decides whether it’s readily identifiable? If it’s not going through the IRB, then whose
responsibility to tell me whether that’s readily identifiable? Yvonne Lau: Okay. Let me just go there. The Common Rule doesn’t say who needs to determine
that, but most of the time you would find that institutions would not allow their investigators
to make their own determination because if you think about it [inaudible] if they make
the wrong determination, right, if somebody was not experienced and who really don’t have
experience or good understanding of these definitions. Then if they make the wrong determination,
then you can get the institution into trouble, right? Because the FWA, the institution [inaudible]
and the money is given to the institution. Institutions generally, institutions receiving
the money would leave this determination to their HRPP program staff, the human research
protection program staff. And some of these people could also be designated
IRB members as well. What I’m trying to say is it doesn’t need
to go through that formal regulatory required IRB process. How they want to do it is up to them. Your question is really meaningful here at
this point because a few days ago, last week we had this big data and health research conference. And people are saying that a lot of the data
nowadays, even if they don’t have the identifiers on it, you can’t really pretend that they
are not fairly readily identifiable, if you like. And so the encouragement for institutions
to really think seriously about this problem and going forward how do you want to — do
you want to have policies? How do you want to think about it? I know here that protecting human subjects
is not the responsibility of a single entity. It’s a shared responsibility. And I think that as it is, for the regulations,
we form the basis. And maybe there’s room to go more strict. But on the other hand, we also get a lot of
pushback by the research enterprise that, hey, you guys are already giving us too much
trouble and the mountain is already too big to climb. So you have to find the balance there. So we all recognize that there may be reasons
for certain research to — that the researchers pay more attention to in terms of protecting
people. But then there are also situations where it’s
really, really minimal risk and very benign. So do you really want to have all these regulations? And that is the reason why the revised Common
Rule, there is a built in for the Common Rule agencies to be able to respond to the changing
environment and the changing landscape with all this technology, the amazing ability through
AI and stuff like that. So there’s this built in mechanism where every
four years the Common Rule agencies are going to have meetings together and talk about whether
they want to look at the meaning of the definition of identifiability and maybe make it work
for the changing times. So we talked about not human subjects research. We’re moving to human subjects research, things
that are human subjects research. So secondary research identifiable. All right. So this research is secondary research with
identifiable information or biospecimens. So when you have such a situation, all right,
you want to then ask if the research can be conducted under one of these exemptions in
the revised Common Rule. Right? These are the exemptions that are available:
4, 5, 7, or 8. But I bolded 4 because that’s going to be
your go-to one. All right? 5 refers to demonstration project, benefits
programs. If you are doing one of those, you know that
you are potentially a 5. 7 or 8, these are new ones, and I’ll talk
about them. But because they’re so new, I don’t think
anyone’s using them yet. So 4 is your go-to one generally. So if none of the exemptions work, then it
will be referred to as non-exemption subject research for which the IRB review and approval
will be required to be done according to the regulation. There are a whole bunch of things that you
have to follow in order to do this kind of regulatory required review. Now, this is going to be confusing. That [inaudible] coming out. I’ll talk about that later. So what does it mean that research is exempt? So research activities that meet the conditions
for an exemption category, one of those that we just talked about, are exempt from the
typical requirements of the Common Rule, meaning the regulatory required IRB review and approval. Institutions generally would rely on — answering
your question again — experienced individuals in the IRB office to make exemption determinations
instead of leaving this to investigators. Making exemption determinations are not equal
in our mind under the regulations to the kind of IRB review and approval that are required
under the regulations, which is more complex, more formalized program. The revised Common Rule introduced this new
concept of limited IRB review. This is the thing I was going to say earlier
on that is causing confusion. This is a one-off IRB determination. And it differs operationally from the regular
IRB review and approval process we talked about. Now, we’re going to come back to this process
a little bit later. Limited IRB review is only required for certain
exemptions. For our purpose, this is required for the
exemption 7 and 8 determinations, not the 4 and 5. So I already told you that exemption 4 is
your go-to exemption for secondary research use of information and biospecimens that are
initially identifiable to the investigators. Now, this exemption has been expanded. And what you see on this particular slide
— I’m going to show both of them now. They should be very similar to you because
they’re kind of what’s in the old rule already. Provision 1 is exactly the same. Nothing has changed. If the identifiable materials are publicly
available. Nothing has changed there. Or 2, provision 2. Provision 2 is essentially the same, but we’ve
changed the wording a little bit and added another requirement. So I’m going to read this to you. Information which may include information
about biospecimens is recorded by the investigator in such a manner that the identity of the
human subjects cannot readily be ascertained directly or through identifiers linked to
the subjects and the investigator does not contact the subjects or re-identify subjects. Let me tease that apart for you a little bit. So this would be the situation where an investigator
may be a physician who has access to a whole bunch of physical records and they know they
can see the identifiers obviously. But they want to use some of this patient
record information for their secondary research. All right? So this is possible because that information
is collected generally in the clinical routine clinical care. In that process, what they would propose to
do is, okay, I’m going to do the secondary research. I’m going to download only information related
to the progress of the disease and certain details about the disease, but I’m not going
to include any of the identifiers or identifiable information with my data set. And once I have that and then I’ll take it
away and I’m going to do my research. Right. So you have a situation where initially, yes,
they can see identifiable information, but as they create their data set for their research,
that is stripped of the identifier. And I do mean that you have to apply the same
standard now. So once they have that data set, you have
to look at it, and you have to apply the standard. So with this information here, can your researcher
here readily link them back to the living individuals. Again, this is subjective. This is through a determination. And sometimes in a rare situation where you
have a researcher who’s dealing with some very rare disease, all right, it’d be hard
to argue that looking at what they’ve got, even though they have no identifiers there,
that they cannot actually link them back to living individuals. So you have that situation, right, that you
want to be careful about. But that’s a rare situation. In the new one, you see that we’ve added the
extra requirement, which is that the investigator does not contact the subject or re-identify
subjects, making it quite clear that really if you’re going to use this exemption, you
better make sure that the purpose of this to be able to use this exemption is that you’re
not going to be thinking about being able to link them back to the subject. This is a kind of protection. I was not entirely correct to say that provision
1 had no change. There is one additional flexibility that is
added. So in the past, under the old rule, there
is word existing. So existing material, existing information. And people used to think, well, if it’s not
existing, how am I even going to be able to use it or study it. Right? And the term drives people mad. So we removed that term. It didn’t mean that. But now we’ve completely removed that term
so it’s not there anymore. What it tells you is that, okay, if you continue
to have relevant information or information coming in, because the continuously new subjects
being added to the pool, then you can continue to use that additional information that comes
in. So there’s no timepoint where in the past
it would be that, okay, well, everything needs to be there when I actually submit this protocol
to the IRB for their review. Anything that comes in afterwards, I cannot
use anymore. Now you have that. You can use it. MS: Let’s try to find a distinction between
— like starting their research, but non-human subjects research and human subjects research
under this exemption. Let’s say there’s an entity that has the PII
of the subjects, and then they send data to another entity, entity B. They just send the
clinical data, not the names. How do you know that investigators from B
couldn’t get the data from A or see it somehow? In which case, it would be more like this
exemption rather than non-human subjects. Yvonne Lau: Okay. So I’m going to answer half of your question,
and I think if we have time, we’ll come back to answer the rest of the question. So the half that I’m going to answer now is
that if you have a group of researchers, and they’re asking — so they belong to Institution
B, and they have some contacts in Institution A where Institution A investigators have a
bunch of this information data that [inaudible]. And apart from supplying that information
to B, right, A has no role. Basically, they’re not collaborating. I know that investigators might want to use
the word collaborating when they are getting things from people. I would strongly advise that if there is no
other role other than providing you with the data or materials, don’t use the word collaborating
because if you use that, you’re in trouble. All right. So what we are trying to look at is if there
is a clean break. Okay. They may be friends and they might be, oh,
can you give — so you really must advise your investigators. For the purpose of the rule, in order to be
compliant, you really are telling me that you are getting this information, this material
or information, without PII. Right? You cannot link them back to those individuals
and you are not going to do that. In a way, sometimes I think — I mean, supplier
of those materials from the other institution often would maybe ask the investigator [inaudible]. So if you have an agreement that’s been approved,
if you don’t have you might want to make sure that your investigators are aware of that
in order to not be not in compliance. So you have that situation. At the end of the day, institutions, if they’re
running these kind of things, they do actually have policies. Small institutions might not have, and that
may be something that you want to remind them about that. The other half of that question, I’m going
to come back and answer. Remind me. You’ll understand [inaudible] that later on. Anyway, let’s keep going. So exemption 4. What you’re going to see on the slide are
the new provisions that we have had under the revised Common Rule. So provision 3 says investigator’s use is
regulated under HIPAA as health care operations, research, or public health. And the whole point about this provision is
that we don’t want to have two rules that are very similar, that are really looking
for protection to have investigators work through. So what it really means is if investigators
are HIPAA covered entities and that they are proposing to do research and their materials
is going to come under the HIPAA regulations, then just follow the HIPAA regulations. Forget about the Common Rule. That’s what we’re trying to say here. I’m not a HIPAA specialist. Whoever in the room is, then you can interpret
it. Note that HIPAA only applies to information. That’s what we know. It doesn’t really apply to specimens. And if you want to know more about it, there
is a really good discussion at the Secretary Advisory Committee for Human Research Protections
a while ago. And that discussion, there was also somebody
who gave a presentation. Mark Barnes gave a presentation about how
to think about this HIPAA provision. And then it was followed by SACHRP members
discussion on this topic as well. So if you’re interested to really understand
about this issue more, then go to these videos. You can access them in two ways. And then the fourth provision really applies
to strictly information data that was collected or generated by the government for non-research
purposes. And I know that there was some confusion about
that. We don’t have guidance on that yet. Especially there’s some confusion with [inaudible]
as to what constitutes government data. I don’t have any expert information to elaborate
on that, so I’m just going to [inaudible] now. So I said we would talk about the new exemptions,
7 and 8. Exemption 7 is the storage and maintenance
of identifiable private information or identifiable biospecimens for secondary research. So one is for storage and maintenance, and
8 is for the use of it. Notice that unlike exemption 4, provision
2, these two provisions allow you to keep the identifier. Just like exemption 4 — and I forgot to mention
that in the last one. 3 and 4, exemption 4, provision 3 and 4 allow
you also to keep the identifiable information. All right. But then you have to follow with certain privacy
rules and protection, right? Exemption 7 and 8 is the same. Both require the use of something called broad
consent. I’m referring to broad consent as a term of
art under the revised Common Rule. And we’re going to go and talk about that. And then it also requires this new entity
called limited IRB review. Generally, it’s for privacy and confidentiality,
protection, and certain aspects of the broad consent. So again, these two exemptions require this
new thing called limited IRB review. What is it? It is a review that is going to be done by
an experienced IRB member. It resembles the expedited review mechanism
that you guys are familiar with. And then it’s only a one-off situation, so
one time. And there’s no annual continuing thing going
on, so you don’t have to keep going back to the IRB to do this. And what they’re reviewing is also not what
we ask them to review under the proper formalized IRB review and approval process. We don’t need them to go through all the criteria
or review under 46.111, for example. What they are required to do is to review
what is specifically described under those exemptions 7 and 8. And they’re very complex to explain, so my
advice would be just if you’re interested to use, go [inaudible] determined. The conditions that need to be determined
in order for the exemption 7 or the exemption 8 to be able to be used. So we come back to this flowchart that we
just saw. So we move on. Is it human subjects research? We said yes. The next question you want to ask is if it
exempt human subjects research, right? And if your answer is, yes, it’s exempt, whether
or not it requires initial IRB review one-off, that’s fine. Once it’s exempt, it doesn’t require the formalized
regulatory requirement or IRB review and approval [inaudible] clinical research, for example. On the other hand, if the answer to that question
is no, then you really move on. And that yellow box is really the full force
of the rule, if you like. It would come under that [inaudible] research. Moving forward, then, away from the exemptions
and we continue into that yellow box, the informed consent options and requirements
for secondary research. In other words, if you actually then require
— if it’s non-exempt human subjects research, you require IRB review and approval. And the other thing that you require would
be informed consent, right? And these are the options that are available
for non-exempt secondary human subjects research. You have the standard informed consent that
we’re all familiar with, right? That you go and ask people for their consent
for whatever that you want to use their data or their biospecimens that’s been collected,
that you want to ask their permission to use this material for this secondary research. Okay. So you go back and ask them for it. That’s one option, and it’s an option that
is available even under the old rule, right? Now, the other one that is being introduced
new is this broad consent. Again, broad consent is defined under the
new rule, and I’ll talk about that in detail a little bit later. Then you have this other option, which is
the waiver of informed consent, right, if the conditions are met. And this waiver has been very much the go-to
option for researchers who are doing secondary research that are not exempt, secondary human
subjects research. These are the standard four criteria that
most of us are familiar with if they’ve been interacting with researchers on this. You can read through them, but what we’ve
added is this new one. The IRB must determine that the research could
not practically be carried out without identifiers. Another way to think about it is that in order
to do the secondary research, the investigators absolutely need to have the identifier in
order to be able to do this research. That’s really what it means. All right? Okay. Now we’re going to talk about broad consent. The term of art under the revised Common Rule,
it’s a new option. It’s an option. Nobody is required to use it. If you don’t want to use it, you don’t like
it, don’t use it. If you like it and you think that it’s great
and you want to try to go ahead and use it, then you have to know what it is. All right. It’s an option. It’s permissible only for secondary research
using identifiable private information or biospecimens. So only for secondary research. So if you go back and try to think about what
we talked about, how we think about secondary research, meaning that those are the items
that were collected for non-research purposes by clinical care or for some other research
that’s got nothing to do with it. If you have those materials and you want to
use this consent, this broad consent, you can go ahead. It is a means to enable subjects to agree
to a broad range of secondary research studies when details of such research may not be available. You remember our standard informed consent. You have all the requirements. The additional requirements. Essentially, it boils down to you need to
be able to tell your potential research participant quite a bit of details about your research,
its purpose, their risk. And so if you don’t even know what research
you are going to do down the road and you know that you probably want to keep this material,
you’re going to probably use it for some of sort of research down the road, but you just
cannot point it down to what, this may be the opportunity for you to think about asking
for broad consent. MS: Is there any consideration to potential
commercialization? It’s an important issue. Yvonne Lau: I don’t remember off my head,
but I can come back to you after looking at the 116, what is the requirement. You might have to mention — I don’t think
it stops you from using it, but you might have to mention it. MS: There has to be language. Yeah. Yvonne Lau: Yeah. It might be that. So I have to come back to you on that. So the broad consent may be obtained at the
time when the standard informed consent is obtained through the research interaction
or intervention of the subject. So in other words, when you’re doing clinical
trials, you have a specific protocol and you’re asking subjects to participate in that protocol. And you are collecting a bunch of things from
them, but you already anticipate whatever I’m collecting from them now for the purpose
of this clinical research that I will probably want to use it down the road, but I can’t
actually yet describe what that down the road research may be. Well, this may be the opportunity for you
now to incorporate and add this kind of broad consent option to it when you’re asking for
the standard informed consent. Or it’s a non-research setting. So you’re going to see a doctor. Let’s say my health care provider is Johns
Hopkins, and I go to see them, my health care physician. And let’s say Johns Hopkins, being a big research
center, they’ve decided that they’re going to ask people for broad consent now, from
now on going forward for all those patients who come to them for normal clinical care. And it’s up to me whether I want to give it
to them or not. So the use of broad consent gives people also
the advantage of being able to qualify for these exemptions 7 and 8 that we just talked
about. You don’t have to use — so if you get broad
consent, that doesn’t mean that that you have to use exemptions. You can if you meet other conditions for the
exemptions. Because some people might think, well, I’m
just going to use broad consent because it’s just generally better and more respectful
of people. And that’s fine, right? So if used, all of the elements for broad
consent must be included. So under 46.116(d), you have to go through
that list and make sure that all of those are in your broad consent, including, amongst
others, a general description of the types of research that may be conducted, the types
of institutions or researchers who might conduct research with the subject’s information or
biospecimen. I really urge that if you are interested using
the broad consent, you go and look at 46.116(d). It’s laid out quite clearly as to what are
required to be in this broad consent, and there’s no flexibility for alteration. All right? So it allows broad use, but it’s not completely,
like, oh, everything under the sun kind of thing. All right? So you have to tell people something. So there’s some caveats with using broad conditions. If individuals were asked and refused to provide
broad consent, so if I’m visiting my health care provider, Johns Hopkins, one of their
clinics down the road and they present me with the broad consent for use of my leftover
blood samples and I say no — in a non-identifiable way, and I say no, then they have to track. They have to track my answers. They have to track my responses and be able
to say this person was asked to provide the broad consent for those. That was described in the broad consent, and
this person said no. And then they cannot go back down the road,
investigators get a hold of some of my stuff, and they ask IRB, oh, can you waive informed
consent for me to be able to use some material with Yvonne’s identifier. IRB cannot waive that because I said no. However, if they don’t want my identifiable,
they’re just taking my blood and they don’t know whose blood in the end that they’re using,
they can continue because that comes under not human subject research that we talked
about right at the beginning. So there is some kind of logistical issues
with the use of broad consent. It needs tracking. There may be costs. There may be logistical difficulties. If you boil down to it, some people would
say, well, if you send a letter out and ask people for their consent and they never respond
to you, is that a no or is that not a no. You have that kind of situation. So some researchers, it may not be an option
that they would prefer. They might want to look for the other options
that we just talked about. So I’m just going to use two more minutes
to just go through some additional [inaudible] that may be of interest to the group. So just a reminder for research repository
storage and data management center. When you’re talking about repository storage
and data management center, you need to actually really think about this as having two separate
components, each of them requiring separate consideration for the purpose of regulation
compliance. So you need to think of one component is the
materials that are going into the repository. And then you can ask yourself all those questions. So these materials that are going into the
repository, are they collected specifically for putting into this research repository
through a research intervention or interaction? If so, they are primary research, right? And you need the formal informed consent or
something like that. Or do they fall under secondary source for
research, which is like they came from other purposes and now you just — whatever’s left
over, you’re putting them into this repository. In those circumstances, you have the option
[inaudible]. In the first situation, they’re really primary
research [inaudible]. Broad consent doesn’t work. Broad consent is only for secondary material
[inaudible]. So if the latter part applies to you, do they
fall under secondary source of research? Then you ask are the materials identifiable
under the Common Rule. And then you follow what we’ve just talked
about in the last 20 minutes. So this is one component of it. Then you have the second component, which
is now the materials are in the repository and people or investigators come into this
repository and they’re asking to use this material from the repository. Now you need to think in those terms now. So you need to ask, well, are the investigators
coming to the repository asking for just simply non-identifiable data or biospecimens for
use? If so, non-human subjects research, right? But if they come into the repository and they’re
asking for, hey, I want to use identifiable material, then you have a situation of identifiable
material with secondary research. And you ask yourself, well, can the exemptions
work? If not, then the options for informed consent,
IRB review and approval. Okay. This is also a common question that people
ask. What is the limitation of standard informed
consent for future unspecified use, right? The question. Can standard informed consent to create a
tissue repository or data bank meet the informed consent requirements for a subsequent study? So can you see this question is kind of combining
the two components that we’ve just talked about? So the first component. You need to have consent, right? You need to ask for consent to put this stuff
into the repository. And so you’re asking whether this consent
can then be used in the second part of it if the second part involves using the materials
in an identifiable way. The answer to this is kind of only if the
consent meets the requirements for 45 CRF 46.116 for the specific secondary research
study. So if you are able to include sufficient details
in it to talk about the purpose, to give people a good idea of what that subsequent secondary
research down the road might be, then perhaps. Now, the further you’re going to move away
from that — in other words, the less you are going to know about what kind of future
research you’re talking about at all, the less likely that this would work. All right. And then you need to think about these options
that we just talked about, the broad concept and going back and ask people for the specifics. MS: For something like the NIH All of Us cohort. You know what that is? What kind of consent did they use? Do you know? Where it’s just collecting data and specimens
from a million people and it’s going to be all types of researchers looking at all types
of questions. Do know what type of consent they needed? Yvonne Lau: I don’t know. [inaudible] FS: I’m with OHRP as well [inaudible]. And we were told that they are using standard
informed consent thus far. So they are aware of the broad consent options. They might moving forward, but right now they’re
using [inaudible]. MS: Is that consent form available on the
internet somewhere? FS: Yeah. You can google the All of Us program. Yvonne Lau: This is the All of Us program. So they’re using that consent to put things
into the repository, right? FS: That’s my understanding. Yvonne Lau: Yeah. And they’re not talking about the second component
yet, right? That consent [inaudible]. FS: [inaudible] secondary investigator speaking
to the data that they’re collecting. This is just the upfront consent to collet. MS: Right. I mean, they’re not planning to have to reconsent
people for specific research. FS: That’s correct. They are not. Yvonne Lau: I don’t know. Maybe they’re only allowed to [inaudible]. So these are just other things that were new
under the revisions. So there’s a notice requirement. A new requirement. The new basic element. Notice the basic element is now under 116(b)
whereas previously it was under 116(a). And the new additional element, referring
to the informed consent, it’s moved to 116(c). So notice has been added. All right. So for secondary research, for the basic element
of notice regarding possible future use of data stripped of identifiers. The purpose of this is really telling people
when they’re being asked informed consent and they confirm and so on that they’re aware. Having that on the informed consent that they
know, okay, my materials without identifiers could be used downstream. This would be the most common situation. The regulation does allow that if you decide,
if you’re working with tribal groups who are very sensitive about their information and
where it goes, and you want to promise that you’re not going to use their data even without
identifiers [inaudible] in other purpose because they’re very concerned about this, then you
can also promise. The notice can say that we will never use
your material again [inaudible]. So it’s a notice. And for the new additional element, there’s
a notice about whether research might include [inaudible] to let people know. So this is just a summary slide. Options for secondary research using information
or biospecimens with identifiers retained. So if your researcher is thinking, okay, well,
I want to have identifiers retained for the secondary research, these are your options. Right? Just repeating what we’ve just said. I’m not going to go through them. Just a reference slide for you all. And don’t forget, the secondary research with
information or biospecimens cannot be linked back to individuals or not identifiable can
be either exempt or not human subjects research. And that’s it. So I want to come back to that question that
you had earlier on that I said there’s another part to it because as you asked it, it also
occurs to me that institutions could be collaborating with one another in a cooperative research,
right? So you have Institution A that is doing the
clinical trial and collecting all the data and stuff like that. And they incorporate an Institution B that
specializes in certain kind of analysis. And so this is an actual primary research
situation, even though you have multiple players. It’s not a secondary research situation. And so what happens is that Institution A,
once it’s collected that through the interaction and intervention for the purpose of this research,
they pass that material without identifiers to Institution B investigators because they
have their expertise in doing certain analysis. The way we think about Institution B investigators
is that they are also investigators on this team of doing primary research. So even though they’re receiving the material
from a different institution, they are — these are not secondary researchers. So that’s really what I wanted to make sure
that you’re aware of that. It’s a cooperative research situation, and
they’re all doing primary research. Now, there is a provision in the regulations. I don’t want to go into that because it’s
too complicated, something called engage [inaudible]. And it is possible that the Institution B,
because they’re researchers, even though they’re involved in this primary research, that because
they’re only getting materials, that there is an agreement there that they’ll never be
able to link them back with what they have to living individuals, that they can under
those circumstances working under that institution, Institution B can be considered as not engaged
in human subjects research. And they don’t have to have a separate IRB
review of that. Now, going forward, because there is a new
provision in the revised Common Rule that requires single IRB review for cooperative
research but there’s only one big review and one single [inaudible] as well. Carol Weil: Great. Thank you, Yvonne. Yeah. We do have a couple questions from remote
that I think we’ll get into. I know we’re coming up on the 12:00 hour. Would whole genome sequencing be considered
easily or readily identifiable at this point in time? FS: [inaudible] would you like to answer that? FS: Sure. Currently, our interpretation [inaudible]
would not in and of itself unless you have [inaudible]. Keep in mind, as Yvonne noted, that there
is a reassessment of identifiability every four years and also incorporate it within
the new regulation requirement that there be [inaudible] determine whether they would
enable information to be identifiable and thus should be construed that way under the
rule. So whole genome sequencing is actually one
of the first technologies that we’ve submitted to the regulation itself to look at to see
whether it should in fact be considered to cross the threshold of identifiable private
information. So the answer is not currently, but that could
change. Yvonne Lau: As it is, it is kind of like — you
can draw the same analogy with my fingerprint analogy that I talked about earlier. It’s uniquely identifiable individual, but
if you don’t have the corresponding information [inaudible]. FS: Right. And I know you mentioned, Yvonne, that there
isn’t a date set as yet for the first meeting that is going to constitute this periodic
four-year review. But do you have any sense of what that content
of that meeting will be like? Will there be involvement from all the Common
Rule agencies? Will there be a notice and comment period? Do you have any kinds of details of that sort? Yvonne Lau: I’m from the division of education. I don’t [inaudible] who is the office director. She might know more. FS: I mean, the regulation itself requires
collaboration [inaudible] that will occur. There has to also be consultation with experts. So this isn’t something that we do in isolation. Yes. This will be an open process. Once those plans do become known, they will
be shared [inaudible]. Carol Weil: Great. Okay. Thank you. And then I think I’ll make this the last question
because we’re running up on time. Are there examples in the research community
that you’re aware of of groups that are using the broad consent provisions? And if so, how is it working? Yvonne Lau: I’m not aware. I’ve heard that people are starting. FS: I’ve heard of starting [inaudible] using
it. I haven’t heard much yet. It might be too early to know how it’s actually
operationalized, received by the patient or research subject community. So I don’t know, but I do know it is being
used. Carol Weil: It is being used. Okay. That’s good to know. And so I do want to be respectful of everyone’s
time. We are coming up on the 12:00 hour. Let me thank again Yvonne and Julie for your
time today and thank you everyone for attending. I hope you all join us for our next ENRICH
forum, which is just one week from today on Tuesday, October 1, at 1:00 Eastern time where
we’ll be discussing the controversial topic of employing ancestry testing as a surrogate
for race in cancer research. Thank you.

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