psoriasis drug

thank you for joining me. i'm carrie kennedy, i'm a senior attorney with the hs office of general counsel. we advice in particular the national institutes of health. my particular backgrounds include human subjects research, and the clinical center which is

the nih research hospital. today we'll be talking about some of the legal issues that occur in clinical research. i'm trying to advance my slides here. do we have a backup? all right. we're back.

so the objectives today as you can see from slides, we're going to discuss the history and elements of informed cop sent for clinical and research care. summarize the evolution and types of advance directives and discuss issues regarding children.

we'll exam issues related to medical records, protection of altty and privacy. we'll discuss authorship rights and protections of legal liability for federal employees and non federal clinical researchers in particular at nih clinical center.

we won't go into a lot of detail about technical transfer issues. i understand you have another lecture on that particular topic. so before we get into the crust of this slide with the resources and legal background, there is a lot of poem signed up who are --

people sigr?" up who are international, not rolled in the united states. to give them a background, in the united states, we give the most deference to the constitution. after that, becomes -- the constitution at the highest

level. next, laws or acts based by congress. those are codified in the united states code or usc. typically below that you can have an executive order pie the president, which is a directive to do something.

fold by regulations. regulations are substantive rules passed by federal agencies as authorized by law. so as authorized by a united states code oract passed by congress, the agency can take that authority and make its own regulations and oversee those

who are subject to the regulations. below regulations are federal policy. so that's the legal framework of what we'll be talking about today, to give you that background. so as you can see on the slide,

a large focus of our discussion will be on 45cfr46. code of federal regulations, where agencies publish their regulations to make them official. the hhs regulations are at 45cfr46. 45 is an hhs specific cfr.

and you can see their ra five subparts to the hhs regulation. part a of the hhs regulations is often called the common rule, because 15 other agencies have the same exact regulation. it will be found in a different part of the cfr but it's the same [technical difficulties].

okay the echo is gone. so they may not have, typically do not have sections b through e like hhs does. but part a is the uniform for those 15 agencies. it's easier for implement when we talk about how to regulate research involving human subjects.

there are three other agencies and departments in the united states that follow what we call the common rule. as a matter of practice, that does -- they have not actually form ice -- formize it in a regulation. the group that has the oversight

authority for 46cfr, 46 for hhs, called ohrp or office for human research protections. they are an hhs operating division. similar to how nih is abhhs operating division. nih has an office that oversees how nih implements its own --

how -- i'm sorry. how nih implementsxd 45cfr46. this is a policy group. that's for those who are at the nih or work at the clinical center or in different institutes or centers, ics at nih, that office is ohsrp. so i know sometimes the wording

confuses people. those are different offices and housed in different operating divisions of hhs. ohrp is the regulatory troupe.jf ohrp is an nih policy group that oversees implementation and compliance at the nih for the neural program.

the neural -- intramural program, this is a lot of background, the intramural program are those staff researchers and clinicians who workã§(pã¡ nih or nihã‘i approved sites toã§ã³ perform research on behalf of nih. it's different than what we call

our extramural researchers, those are our grantees who gives nih -- who nih gives money to fund research. so a little bit of history. as you probably herd, in some of your earlier lectures, in case you haven't, hhs came out with its first set of human subjects

regulations in the 70s. in 78 the first essentially bioethics commission in the united states foremaned the belmont report. that identified what they countdown fundamental ethical -- they considered fundment ethical research. you'll see that fda has its own

hum subjects regulations. fda is part of hhs, but fda is its own -- in itself, is its own regulatory entity. it has its own rules which it oversees. 21cfr50, the 21s. cfrs are also hhs, just so you know. cfr50 are the fda regulations on

human subject protections, and 56 regards the irb or institutional review board. irbs are the groups that are tasked to oversee and assure that the protocol submitted to them and approved as required by the regulations meet the so parts 50 and 56 really are v

similar to 45cfr46 subpart a. part 312 for the fda, investigational new drug applications f you're testing part of your research request involves a drug. 812 regards investigational device exemptions. so as another aside because it's

timely right now, a few years ago in july, 2011, the hhs released on hhs itself released in the federal register, the way you notify the public of new regulations, it released an advance notice of proposed rule making to suggest modifications to the common rule and asked for

public feedback. and that occurred in 2011, hhs received comments, considered them, and then moved forward in what they just released in september of 2015, which is the notice of proposed rule making. and that's a more solidified concept of what might be

eventually the final rule. once the final rule comes out, it will be binding. and it essentially will replace the current terms of 45cfr46 subpart a. the final rule hasn't been released yet so we're still operating with the current terms

of 45cfr46. part a. as well as for hh.s, b through e. for those members of the public who wish to make comments on the proposed, the comments are due january 6. here, the information, i

provided a website for you to find more information about the nprm. and so if you have furthernist i encourage you to look at the information. there is a lot of proposed changes and we can't talk about them today unfortunately.

there is not enough time. i encourage you to take a look at it. so now for informed consent. so now we know that informed consent is essentially the bedrock principle of medical care and research care. it was developed in part, the

idea of inform consent, through common law, which is precedent set by court cases and judicial decisions. as opposed to law that was passed by legislators at either the state or national level. the law began in terms of informed consent, looking at it

as a issue of a battery claim. so in the law, for patriarchs you have to prove -- battery, you have to prove physical touching regardless of harm without consent. one of the first cases known for considering these types of informed concept issues as a

battery concept was the one i have on this slide before you. and that one, the plaintiff claims that he had agreed to an explorery examxd related to stomach fine broad tumors. during that exam, the surgeon removed the tumors, which the patient or plaintiff, then, said

caused him additional distress and surgeries. so that was the case where the court considered the additional action by the providerxdko jf [technicalxd difficulties]. further developedjf by various intellectual bodies. some of them i have listed on

this next slide. the neuronburg code was developed after the world war ii developed standards for physicians and scientists who conducted biomedical experiments on concentration camp prisoners. and this code became the prototype for many other codes

intended to assure that research involving human subjects would be carried out in an ethical manner. this was replied upon in the hhs belmont report that i referred to that actually led to the hhs you can see the ideas of informed consent were further

solidified within the courts. the courts row framed the issue as negligence or malpractice action, as opposed to an action of battery. negligence, you have to prove there is a duty owed. the duty is breached. damages result and that the

damages is actually caused by the breach. in the case on this screen now, this was the first case to actually use the form -- i'm sorry, use the term informed consent. this was a case where somebody, 55-year old has circulatory

problems and under went surgery, resulting in lower paralysis. the court determined that this was a rack of informed consent. that the duty to disclose -- there was a duty to discloser risks and obtain informed concept before performing procedures.

and so that the patient should have been informed of these details again in advance, including dangers. the standard use in this case which has been adopted and still the standard today is the reasonable patient standard which means what would a

reasonable patient in those circumstances want to know? this is a -- as opposed to a reasonable physician standard.fã¡ so the informed consent per says, today -- process. today, courts focus on the quality of the concept. it's not legally effective

unless the patient understands the procedure and the treatment and the risks. the legal standard is the sameã±r certainly forã±r research. so in research, ends in medical terms, the concept needs to be voluntary. can't bexd against somebody's

will. the disclosure has to include relevant information, has to be comprehensible to the person, either verbally or in writing. appropriate reading level, generally t regulatory requirements are very similar to what you would see in the

medical context for informed there are some additional ones, such as 45cfr46, which we talked about earlier. part 116, has additional requirements for informed one of those is you have to be clear and say what you're doing right now is the participant,

you say the participant in your conversations and documents is your participating in research. so it's clear, it's not necessarily medical care, butxd research. thatx$$vã¡u try to explain to the best of your ability the duration of the research, theã±r

purpose, what if any will be experimental as part of the that your participation is voluntary and you can withdraw without loss of benefits. and the counterpart of the consent requirements under the fda regs is 21cfr50.25, in case you are curious.

so what must be disclosed? the informed concept process. you generally diagnose the following information on the slide. you don't have to diagnose every possible risk. it's based on the standard, on the situation, and a lot of

degree, to the clinician's judgment. and often people ask how much there is of concerns about what do we say in the consent form. we're concerned about the length, risk, how much science. and the research for --r& research coo]uhow much must

be explained. and, again, it's about the discretion and understanding your patient population. what they need to know. to give you legally effective informed consent. again it's not every possible risk.

but it has to be a reasonable standard. this slide explains who can obtain informed consent. it's generally up to the institutional policy, who can obtape it. it has to be somebody not only effective communicator but has

an indepth understanding of the research procedure or if it's a clinical issue, the clinical procedure. and then the other question is on the counter point of obtaping it, you can actually provide the concept. a competent adult can provide

informed consent in the ups. we as a legal matter, assume that once somebody has turned 18, they are competent to make their own legal decisions. if this is no -- if the adult is not competent or if it's a child, it would be the person's legally authorized

representative. now, the term legally authorized representative in the research context has a specific definition. and it's can find in both the hhs regs and fda regs. as another person such as the parent, or legal guardian or

entity such as child protective services or the court, authorized under law to concept on behalf of the perspective subjects. if they're competent adults they can consent or refuse. if somebody lacks as an adult, capacity to consent, you can

provide emergency clinical care, if you're a clinician. you can provide emergency clinical care if you can't obtain consent, per the patient or the surrogate. however, research is another story. generally it's not appropriate

to initiate research without obtaining legally effective concept there the patient or their representative. which is why advanced directives and surrogates particularly useful in the research context. so now let's get into the types of surrogate or substitute

there are 3 types as you can see on the slide. the first is legally appointed gardens, then we'll talk about advanced directives. there is two types, living wills or durable power of attorney for healthcare. the third type we'll talk about

is substituted consent. a guardian. again, in the u.s. if you're over 18 there is assumption that you're competent. if an adult looses capacity or never had capacity by the time they turn 18 because of the developmental delay, let's say,

one can petition the court for guardianship. this -- there is a whole legal process that the court goes through. there is fact findings, usually there is an attorney representing the person who is being questioned in terms of

their capacity. and then the court makes a decision about whether or not that person, which we call in the legal world the ward, if it's deemed that they don't have capacity, is able to make certain legal decisions on their own or not.

if a guardian is appointed, the -- so let's say a guardian is appointed for healthcare decision making, the guardian, not the ward, consents and can give legally effective consent. states have different laws about what a guardian can and cannot consent to. for instance, some

states, i'd say maybe even many states, have lays restricting guardians for enrolling wards in medical or biomedical research or clinical research. and that is -- that comes from legislative action by the state in order to protect the ward. you can imagine where those

types of laws might have arisen out of. if a guardian is a guardian of a state that has such a law, at the clinical center what we do, we accept guardians from 50 states where federally -- we have federal exclusive jurisdictions so we're not

subject to state law per se by law. but when it comes to guardians, we follow the law of the state where the guardian was appointed. and so if a guardian doesn't have legal authority to consent to research on behalf of the

ward, the guardian essentially would immediate to petition the court for the additional authority to do so. so let's move on to advanced directives. as you can see, these are the two advanced directives that i discussed, i referenced before.

a living will is very specific to thisã§ã³ situation, discusses life saving measures that you would or wouldn't want, such as a feeding tube, antibiotics, and very broad conditions like persistent vegetative states. and as opposed to a durable power of attorney for

healthcare, that is appointing a proxy decision maker. appointing somebody and giving them flexibility to make determinations bass on a or situation that make occur in the future. the flicks exhibit allows for -- flexibility allows for a wide

variety of factual decisions as well as changes in technology, research, and medicine that you might not be able to anticipate through a living will. the word durable is added, and specific. it has a specific meaning. it means that the power of

attorney, somebody is assigned, lasts beyond their capacity. so if you assign a power of attorney, depending on the state law, that often times you have to specify that it's durable. otherwise that pair of attorney is only considered to have authority when you're still

competent. if you loose competence, they might not have the authority to make decisions for you. and again, that is variable state by state. and i mentioned -- i'm sorry. in the prior slide, i didn't mention but it's written, that a

living will, usually relates to terminal conditions. the term terminal also varies state by state as decided by a legislature, sometimes court cases. generally means a condition from which there can be no recovery including death and increasingly

states have been adding pvs. it has been relevant. the way it's been relevant is in the courts. we might all remember some off these cases that i've given as examples on this next slide. these tree cases. i'm happy to talk in detail

about these cases with anybody if they want. but the general take away is that generally, courts and states favor the preservation of life unless there is career written statements by the -- clear written statements by the person before they lost capacity

to speak for themselves, appointment or proxaby that person. progressiony by that person. for instance, in quinnla non life threatening injuries, that was a 1979 case. it's -- quinlan case, the person was in a vegetative state.

it wasn't known what her wishes were. so the state, it argued, had an interest against anybody terminateing life. the courts found that the state interest weakens as the individual's rights to privacy grows and the degree of bodily

invasion increases and the prognosis dims. the cruzan caesuras a woman 25 years old, was in an accident, and became also in persistent vegetative state. she had a conversation about a friend about herwishes. she was about what level of

evidentiary standard the state could require a family to prove in order to remove life sustaining support. and the standard the state wanted to use was clear and convincing evidence which has a whole legal term and lots of legal precedent behind it that i

won't go into. this case went to the supreme court. and the court stated that that was an acceptable standard, that's a very high standard but it was acceptable, given the circumstances. it was remanded to the state

court for ultimate decision and what happened was the state withdrew its claim and essentially seated to the family to make the decision that the family felt was in the preference of miss cruzan. the take away of the legal summary is a crux of that case,

was that the state's interest in preserving life was challenged by the family's constitutional ability to refuse care which is a 14th amendment due process. they were due their due process. prior to taking the liberty. the liberty was the right to refuse treatment so the courts

were balancing the liberty interests verses the state's interests. and in the schiavo case, that highlights the advance directives and living wills can do to prevent the,iã±rrguess,lpfã¡ã±r unknowns in future unanticipated inã±r that case, miz schiavo

arrest, and coma, there was a feeding tube inserted. her husband wanted itw3xdremoved. herparents petitioned against removal. thisokã§ã³ became a verycontroversial public issue. the congress commented on it. president bush at the time

commented on it. there were 14 appeals in the courts of florida, five appeals to the federal, four denials pie the supreme court of the united states simply about this one case alone. it demonstrates the legal issues when you have encompassitated

adults. -- incap passitated adults. the last point i'll make regards the patients self-determination act. that requires that hospitals who accept medicare and medicaid funding to inform patients about their rights to execute advanced

directives, it's really a floor in terms of rights, not a ceiling. it prevents the hospitals from discriminating patients to make advance directives, and it's intended to protect atobmy and self-determination. so we've talked about guardians.

we've talked about advanced now we're going to move on and talk about surrogates. surrogates, the power of a surrogate varies from state to state. some allow surrogates to make decisions only when it's known but the patient's wishes are.

some states like maryland allow the surrogates to make the best decision and make a decision in the best interest of the patient. the forms also vary state by generally has to be voluntarily executed, written, signed, witnessed by two unrelated

people. for medical providers, you might be interested to know usually there is no criminal or civil liability. pursuant to reasonable medical and soth pus an onus on medical practitioners to know whether an advanced directive exists so

they can follow it. tissues out the clinical center -- turns out the clinical center not subject to any state law -- to any particular state law but there are advanced directives from outside states or countries, and we allow patients to execute one that we

have here which actually specifically talks about research participation. the last bullet point, some research protocols as a condition of participation require the patient to have an advanced directive. it's anticipated that the

patient will lose cognitive ability such as in an alzheimer's study. so now let's talk about what happens when somebody is a patient or -- without a guardian. without a durable power of attorney.

without a living will. and then they become mentally incapacitated. so they've expressed their wishes previously, certainly if they're documented in the medical record, clinicians can follow those wishes. without them, then there are

certain ways for state law in particular to authorize individuals to give substituted consent for furnishing, but not withdrawing care. on substituted consent, there is a hierarchy. if a spouse or domestic person exists, and the example is the

clinical center policy which mirrors maryland law. if spouse or domestic partner, they can be on the same law. you can't have both, only one or the other. so first is that. and then you can see down the hierarchy.

if somebody higher on the hierarchy exists they're the ones to make the decision. do you have any questions before we move on to the next section? okay. now we're going to talk about children and their participation in research.

a child is a person who hasn't reached legal age to consent. a child is defined by the research regulations. verses not reached the legal age of concept to the research treatments or procedures under the applicable law in which the research is to be conducted.

typically a child is somebody under 18. sometimes different clinical settings. the age might be younger, such as obtaining sexual hillaryhealthcare provision and other at the clinical center, the definition of child is anybody

under 18, not themselves married or a parent. so under the research a child doesn't have the legal authority to consent but they can be asked to assent. generally, the permission is suit there both parents of the child or in their absence, a

legal guardian. there are exceptions and the irb, again, institutional review board that looks at protocols before they're implemented can approve the consent of only one parent as being sufficient, and usually lower risk research. something for clinicians to

perform research. if you have a child who is in foster care, you have to give extra scrutiny to the law of the state, because you heed to assure that the person who has physical custody of the child that is legal authority to consent to their participation

for instance, a foster parent might not have that legalthority and you might need to get it from a court or the child protective services of the i should say when the permission of both parents is required, there is a provision if one parent is unavailable or

deceased, then both parents do not need concept. some in the situation where you're dealing with children, and the parent or legal guardian isn't available. for emergency medical care it can be provided without consent. if a parent or legal guardian

refuses to provide their permission for research, their choice governs. if they fail to provide concept for clinical care, it depends on what the situation is. if the benefits of the care outway the risks sometimes the stated will step in. -- state

will step in or the hospital can seek a court order. and the parent's rights are essentially abro gated and the court will speak on behalf of the child. sometimes, in pretty rare exceptions i would say, you can have mature minor exception.tw

usually choser to 18 years old, but older child can go through a court process and petition the court to be deemed, z adult for the purposes of giving their -- making their own legal and thelpxdã§ã³ã§ã³ court usuallytries to assure thatok this minorpb0'=9 fã¡ nderstands theã‘iunder 18ã§ã³ã‘i

consequences andfã¡ permanency of their medical decisions. sometimes thisok comes up intheã‘i case, one example could be jeff's witness s. [technical difficulties]. and there is a lot of balances to be had in this situation.

such as how risky the trial is, what clinical care might noticed to be provided, what the -- might be provided, what the child's future medical state may be, and why the parent can't attend. convenience isn't usually accepted as sufficient racial

racial. let's say you're a single parent and you're 9 months principling. that might be deemed a sufficient reason. when a temporary decision maker is invoked, it is the parent assigning somebody to make decisions for their child on the

parent's behalf. the way the clinical center operates, we still call the parent and have the parent possible -- phone as much as possible, and direct the person who is here at the clinical center. so that the parented still

understands around hag some sort of oversight facility. that wraps up our discussion about children in research. so now we can go on to talking about medical records. so basically medical records should contain diagnostic and clinically relevant information.

it needs to be accurate. and it needs to be timely. if somebody looks back on it, it needs to give a full picture of what has happened, discussions, lab results, the like. and the clinical center medical records just like other institutions are maintained to

provide continuous treatment, and they also provide a database for the clinical research conducted within the hospital at the clinical center. again, document care to patient and they plan and evaluate the patient's treatment through them, and sometimes support the

justification of somebody's involvement in the protocol. of course medical records at the clinical center and else where facilitate communication and support adequate discharge planning. and failure to document properly mainly to inappropriate

treatment andlp possiblepatientã‘ilpã‘i harm at the clinical center inxd nih -- now, at the clinical center in nih, medical records are distinct from research records. that might not be true in other types of institutions such as industry.

they contain data about the individual relevant to the research study. so the clinical record, the clinical medical record might be more voluminous than the research record, if the research record doesn't need all the information that's collected in

a clinical care setting. thejf research record, vails the clinical, epidemiologic and bioresearch activities. generally, medical records can rarely be disclosed without the patient or their surrogates and if patients do consent to release their records, they can

consent to release only certain types of records or only providers. certain providers. at the nih there is policies about record releases, if you have any questions, we have at the clinical center,ã§ã³ themedical administration mas, there is

also the handbook. and at the national institutes of health at the federal agency, we are subject to the privacy act which i'll talk about later, which in part discusses medical records disclosure and disclosure of privacy act now the privacyã‘i act.

so the privacy actxd prohibits disclosure of the records of the-- defined on the slide that i've given you. it's basically a record under the control of an agencyã±r from which information retrieved by a name or identifying number of the individual. so generally the privacy act,

passede1 in '74 prohibits disclosure of records to third parties without their written consent of the individual to whom the record pertains, unless one of the 12 disclosure exceptions innumerated in the act would apply. and theã‘i permissible release

without consent is limited and rarely would include identifiable information. some examples when it might be released without written consent would be for law enforcement purposes. or health and safety for emergent care.

so, for instance, again, just the hypothetical. if somebody landed in anã‘i erand the last thing they said before they passed out, they just came from nih clinical center and i'm on this medication and they pass out, the hospital these to to know what medication the person

was on, that might be an urgent medical circumstance in which we would give very limited together for the patient care. there are other rules about how we would do that and how to notify the patient after the fact. but again, it's pretty rare.

the privacy act applies to u.s. citizens and lawful aliens, not to corporations. privacy act rights andã‘ideath.xd they don't extend beyond death. privacy act was enacted to balance the government's need to maintainxd and collectfã¡ information, with the individual

to be protected against unwarranted invasion of their privacy stemming from the federal collects main tins, use, disclosure aboutxd this individuals update theã§ã³ã§ã³privacy act are entitled to their privacy act record with some exceptions, oft(t( course,notably

one would be law enforcement. and individuals are entitled to correction of the record. and related to the privacy act, one can bring suit in court for privacy act breaches. and this is an area in which the united states government, which normally by law cannot be sued,

it has waive its ability, sovereign immuneny, as its negotiation and will allow itself to be sued in this type of instance or violation, in particular circumstances oftheã±r privacy act. notices of any systems of record, so records collection,

for instance, need to be published in the federal register. and the notices site illegalthority for collecting and storing records. so the clinical records here at the nih clinical center would regard patients who are seen at

the clinical centerfor4i,-research. the publication in the federal register alsoxd informs whattype of information will be collected and how it will be used. and the public is considered on notice once it's published in the federal register. violations of the privacy act

can lead to both criminal and civil prosecution. or penalties,t( i'm sorry. so one of the exceptions i mentioned without the privacy act in which you can release information about whom the record pertakes is routine use, one prescribed in the --

register, allow the release in certain situations. so the law defines use as use of a record for purpose which is compatible for the purpose of which it was collected. at the clinical center, a routine use for the clinical center medical records is

responding to congressional inferries. allowing social work department to reach out to local agencies to aid in the transition of the patient or their family back home or get other services that they need. if there is a referring

physician that's taking over care after discharge. and other medicalc organizations or consultants that are connected to the treatment of the patient.ã§ã³ research records, again, different record system than our medical records.

they also have routine uses. sometimes in some of the routine uses i have listed on the screen just to give you a flavor of what they are. you might of heard of foia,q the freedom of information act. this was passed in 1974 after the watergate sandal.ã§ã³

theã‘i idea -- scandal.xd it provides individuals withtheã‘i rightã‘i to access records in the possession of the federal government. the government can withhold information pursuant to 9 exemphasises and 3 exclusions. medical records typically fall

within an unwarranted invasion ofxd personal privacy, an exemption no. 6.xd %=9 under foyerand that pro,e may continue after the death of an individual for the benefit of the privacy of the family. and let's see. -- let's see. foyia as compared to the5a privacy

act is applicable to corporations, so it's what happs is that under the federal tort claim act or ftca, the ftca becomes the exclusive remedy for someone who has a complaint against the government or employees. generally, the ftca prides

immunity to employees for crimes of next relating to conduct that is in their scope as employment. what would happen is if somebody sued in their official capacity relating to negligence actions, related to their scope of their employment, the government would substitute itself for the

individual so the person would no longer have personal and damages were found to be necessary or paid out it wouldn't come from your personal pocket book. it would be from the government. it's a way, essentially, to -- that the government self-ensures

itself. and when ftca matters come up, ftca requires that a claim be filed. you can't go straight to court and file litigation. the claim can either be disallowed, and then the person could file suit, or the claim

could be allowed and it might be settled. and often times, always i should say, those claims are reviewed by the hhs office of general council. and depending on the stage of the claim, if it has become litigation, also, the department

of justice that defends federal agencies in court. but the hhs office general council provides support to the department of justice, in those situations. and i should note -- sorry. it's on the slide. that healthcare professionals,

for example, the clinical center who are not federal employees are required to be insured to maintain professional liability insurance for the reason of the fact that the ftca covers employees. and that is all i have for you today that i was planning on

discussing. if anybody has any questions i'd be happy to answer them. all right! thank you, have a good night!