1 00:00:09,209 --> 00:00:10,543 Monitoring and auditing are 2 00:00:10,543 --> 00:00:13,947 two different terms that kind of get interspersed quite regularly. 3 00:00:13,947 --> 00:00:15,315 But monitoring's actually more 4 00:00:15,315 --> 00:00:18,385 the overseeing of the progress of the clinical trial. 5 00:00:18,385 --> 00:00:23,790 It's kind of more a look at the processes in place, and it does ensure that 6 00:00:23,790 --> 00:00:27,894 the trial's being conducted, and recorded, and reported according to the protocol. 7 00:00:27,894 --> 00:00:32,632 But the auditing is more of that systematic and actual looking at the data 8 00:00:32,632 --> 00:00:36,369 and comparing the source documents to the information that's been submitted. 9 00:00:37,170 --> 00:00:38,405 Is it accurate? 10 00:00:38,405 --> 00:00:42,142 Is the information there that they need to see? 11 00:00:42,142 --> 00:00:45,045 There are various agencies that conduct audits. 12 00:00:45,045 --> 00:00:45,879 The NCI. 13 00:00:45,879 --> 00:00:51,684 We have research programs that provide research trials and studies for us to -- 14 00:00:51,684 --> 00:00:57,090 that are available then to our research programs, sites out in the communities, 15 00:00:57,090 --> 00:01:02,062 and the NCI charges these programs, the ones that generate the trials, 16 00:01:02,062 --> 00:01:07,867 to go out and conduct audits on a regular basis on our research sites. 17 00:01:08,401 --> 00:01:10,503 The FDA has also conducts audits. 18 00:01:10,503 --> 00:01:14,707 It's kind of -- when somebody says they're having an FDA audit, 19 00:01:14,707 --> 00:01:15,742 they're instantly stressed. 20 00:01:15,742 --> 00:01:17,143 And I'll give you 21 00:01:17,143 --> 00:01:21,381 a little bit of information about an FDA audit, but they're important. 22 00:01:21,381 --> 00:01:24,517 FDA carries a huge role of trying to decide 23 00:01:24,517 --> 00:01:27,320 if a drug is actually active or not. 24 00:01:27,320 --> 00:01:31,891 They want to look at the data to ensure that it actually is. 25 00:01:31,891 --> 00:01:35,061 The Office of Human Research Protection, or OHRP, conducts 26 00:01:35,061 --> 00:01:38,198 audits of IRBs and regulatory portions of the research. 27 00:01:38,798 --> 00:01:41,768 The sponsor itself of the trial will do audits. 28 00:01:41,768 --> 00:01:46,039 And then there also should be those internal site audits that are done 29 00:01:46,039 --> 00:01:46,539 locally. 30 00:01:46,539 --> 00:01:50,977 The purpose of an audit, again, is to look at, number one, determine 31 00:01:50,977 --> 00:01:55,248 if the right safety and welfare of those study participants have been upheld. 32 00:01:55,248 --> 00:01:59,219 They're there to evaluate the conduct of the trial and protocol compliance. 33 00:01:59,986 --> 00:02:02,589 They evaluate the site's standard operating procedures, 34 00:02:02,589 --> 00:02:07,026 and they help to verify the integrity and reliability of the data. 35 00:02:07,026 --> 00:02:11,131 And they also help to determine that all the regulatory procedures 36 00:02:11,131 --> 00:02:12,432 have been followed. 37 00:02:12,432 --> 00:02:17,070 For-cause audits do raise the hairs on the back of your neck 38 00:02:17,070 --> 00:02:21,875 sometimes when you think about those because you don't want a for-cause audit. 39 00:02:21,875 --> 00:02:26,212 They're usually related to sites that may be, compared to everyone else 40 00:02:26,479 --> 00:02:30,183 participating in the study, for some reason they're having really 41 00:02:30,183 --> 00:02:34,454 surprisingly favorable results compared to others, might flag a for-cause audit. 42 00:02:34,454 --> 00:02:37,190 Sites had unexpected high enrollment versus others. 43 00:02:37,190 --> 00:02:40,727 The investigator that's conducting a large number of trials, 44 00:02:40,727 --> 00:02:44,631 if they're outside of his or her area of expertise, 45 00:02:44,631 --> 00:02:49,335 may raise a bit of a red flag for a site audit. 46 00:02:49,335 --> 00:02:53,239 And if there had been an unexpected death or deaths 47 00:02:53,239 --> 00:02:57,510 at a particular site that, again, may trigger a for-cause audit. 48 00:02:58,745 --> 00:03:00,713 So what do auditors look for? 49 00:03:00,713 --> 00:03:05,251 I think helping to know that will help improve the quality of any program. 50 00:03:05,251 --> 00:03:08,821 Most audits you're going to look at the regulatory IRB information. 51 00:03:08,821 --> 00:03:13,059 They want documentation of full review, initial review, as well as annual review. 52 00:03:13,059 --> 00:03:15,662 They're going to look at your consent documents. 53 00:03:15,662 --> 00:03:17,931 They'll look at the pharmacy, drug accountability. 54 00:03:17,931 --> 00:03:21,801 They want a verification of the receipt, and the storage, and security, 55 00:03:21,801 --> 00:03:23,770 as well as the inventory control. 56 00:03:23,770 --> 00:03:25,071 And the biggest piece 57 00:03:25,071 --> 00:03:28,641 or portion that they will review are the patient case reviews. 58 00:03:29,142 --> 00:03:32,545 Then, again, they'll going to be looking at the consent, 59 00:03:32,545 --> 00:03:35,949 mostly for signature of the patient, that they're completed properly. 60 00:03:35,949 --> 00:03:37,650 They'll look at eligibility criteria, 61 00:03:37,650 --> 00:03:39,352 whether correct treatment was administered, 62 00:03:39,352 --> 00:03:43,122 what the disease outcome and tumor response were, any adverse events, 63 00:03:43,122 --> 00:03:47,193 and then also they do look at just general data quality. 64 00:03:47,193 --> 00:03:48,561 So informed consent. 65 00:03:48,561 --> 00:03:53,333 They're going to look to make sure all of the required elements are there. 66 00:03:53,333 --> 00:03:57,070 Most of our trials provide the sites with templates, consent templates, 67 00:03:57,070 --> 00:04:00,807 and they sometimes have to modify them to fit local context. 68 00:04:01,574 --> 00:04:05,645 However, sometimes in the process of transferring and working with Word 69 00:04:05,645 --> 00:04:08,581 documents, some of the information may be deleted 70 00:04:08,581 --> 00:04:11,884 inadvertently, or copy and pasted into the wrong section. 71 00:04:11,884 --> 00:04:15,955 All of those things are what auditors will look at. 72 00:04:15,955 --> 00:04:19,626 They usually don't complain too much about adding information 73 00:04:19,626 --> 00:04:23,696 if they feel it's going to help to inform the patient. 74 00:04:23,696 --> 00:04:24,797 However, removing information 75 00:04:24,797 --> 00:04:29,569 that was there for information purposes will result in usually a major deviation. 76 00:04:29,569 --> 00:04:34,741 Was appropriate version of the consent used for all patients at the correct time? 77 00:04:34,741 --> 00:04:35,475 Was re-consent 78 00:04:35,475 --> 00:04:39,512 if consent or the trial changed significantly enough that it required 79 00:04:39,512 --> 00:04:43,216 all patients that were currently on trial to be re-consented? 80 00:04:43,216 --> 00:04:45,051 Were those patient re-consents done? 81 00:04:46,252 --> 00:04:49,589 Was the consent obtained prior to any tests or assessments? 82 00:04:49,589 --> 00:04:53,426 And was it obtained definitely before any study medication was given? 83 00:04:53,426 --> 00:04:56,262 Eligibility. Did the patient meet the eligibility criteria? 84 00:04:56,262 --> 00:05:00,600 They're going to go through every one of the criteria and compare it 85 00:05:00,600 --> 00:05:04,604 to the what the case report forms shows versus the source document. 86 00:05:04,604 --> 00:05:06,606 And it needs to be there. 87 00:05:06,606 --> 00:05:10,977 As far as the looking at the protocol assessments, according to the protocol. 88 00:05:10,977 --> 00:05:12,645 They'll look at the exams. 89 00:05:12,645 --> 00:05:15,648 They'll look at performance status, laboratory test, diagnostic test, 90 00:05:15,648 --> 00:05:16,316 tumor measurements. 91 00:05:16,316 --> 00:05:18,985 They also look at quality of life measurements. 92 00:05:21,087 --> 00:05:21,554 Treatment. 93 00:05:21,554 --> 00:05:25,858 Where the drug dose -- drug or agent administered 94 00:05:25,858 --> 00:05:31,564 as it was designed or said to be given within the protocol? 95 00:05:31,564 --> 00:05:36,336 If it's an oral agent, was a diary/pill count provided? 96 00:05:36,336 --> 00:05:41,574 And they'll also then compare this information to the pharmacy log. 97 00:05:41,574 --> 00:05:45,878 Was the drug administered in a timely -- according 98 00:05:45,878 --> 00:05:50,149 to the time of administration, according to the protocol, 99 00:05:50,149 --> 00:05:53,986 any dose modifications followed according to the study? 100 00:05:53,986 --> 00:05:56,823 And, again, they'll look to see 101 00:05:56,823 --> 00:06:00,760 if any contraindicated drugs were provided or given. 102 00:06:00,760 --> 00:06:01,961 Drug accountability. 103 00:06:01,961 --> 00:06:06,866 Were the agents properly stored in a secured pharmacy area? 104 00:06:06,866 --> 00:06:10,670 Were they stored by protocol and by study? 105 00:06:11,304 --> 00:06:14,707 They do not want to put the same drug 106 00:06:14,707 --> 00:06:19,245 from different studies in the same box or container in the pharmacy. 107 00:06:19,245 --> 00:06:22,281 It really allows error, huge errors to occur, 108 00:06:22,281 --> 00:06:26,085 so they usually want those things all separated by trial. 109 00:06:26,085 --> 00:06:29,722 If some agents are required to be refrigerated or frozen, 110 00:06:29,989 --> 00:06:31,758 the pharmacy should be able 111 00:06:31,758 --> 00:06:35,528 to provide temperature logs to make sure that those temperatures 112 00:06:35,528 --> 00:06:39,699 were -- stayed consistent according to the needs of the drug. 113 00:06:41,367 --> 00:06:44,670 A huge issue that I -- we run into frequently 114 00:06:44,670 --> 00:06:46,339 are the drug accountability forms. 115 00:06:46,339 --> 00:06:49,642 They are busy people, the pharmacists, so they'll go in 116 00:06:49,642 --> 00:06:53,946 and they'll write it down, and they're like, oh, they made a mistake, 117 00:06:53,946 --> 00:06:57,283 and they'll scratch it out, and try to fix it. 118 00:06:57,283 --> 00:06:58,584 And that's considered incorrect. 119 00:06:58,584 --> 00:07:02,922 A single line through, date, and initial and -- is considered a way 120 00:07:02,922 --> 00:07:06,893 to complete an error that might occur on one of those forms. 121 00:07:07,427 --> 00:07:11,030 And most of those DARFs are still in paper form. 122 00:07:11,030 --> 00:07:13,933 They're trying to convert those over to electronic, 123 00:07:13,933 --> 00:07:17,170 which hopefully will eliminate some of those problems. 124 00:07:17,170 --> 00:07:20,072 Were the investigational agents disposed of properly? 125 00:07:20,072 --> 00:07:24,377 If that information was provided within the protocol to allow for that. 126 00:07:24,377 --> 00:07:26,179 Was the study blind maintained? 127 00:07:26,179 --> 00:07:28,714 Were hopefully commercial agents were not used. 128 00:07:28,714 --> 00:07:32,318 And was the drug inventory completed on a regular basis? 129 00:07:32,618 --> 00:07:36,989 We really encourage our pharmacies to do at least monthly checks to confirm that 130 00:07:36,989 --> 00:07:40,126 what's on stack matches what's on the drug accountability form. 131 00:07:42,428 --> 00:07:43,696 Common audit deficiencies. 132 00:07:43,696 --> 00:07:46,599 Failure to follow the plan, investigational plan. 133 00:07:46,599 --> 00:07:49,502 Not documenting information properly. Any protocol deviations. 134 00:07:49,502 --> 00:07:52,839 They didn't follow the protocol according to plan. 135 00:07:52,839 --> 00:07:56,576 Failure to ensure that the consent form was obtained 136 00:07:56,576 --> 00:08:01,147 is kind of the -- I don't see that as much. 137 00:08:01,147 --> 00:08:05,718 I think one issue we see more frequently are the re-consents 138 00:08:05,718 --> 00:08:08,621 not being done in a timely manner. 139 00:08:09,822 --> 00:08:13,559 Failure to maintain accurate, complete, and current records. 140 00:08:13,559 --> 00:08:18,231 Lack of appropriate accountability for the drugs and provided agents. 141 00:08:18,231 --> 00:08:21,968 And then a failure to obtain IRB approval. 142 00:08:21,968 --> 00:08:28,007 Not so much the initial but maybe amendments IRB approvals within a timely 143 00:08:28,007 --> 00:08:33,846 manner is oftentimes is a deficiency that we see within our sites. 144 00:08:33,846 --> 00:08:38,284 Audit determinations usually they're classified into two different 145 00:08:38,284 --> 00:08:42,021 categories, lesser or minor deficiencies versus major deficiencies. 146 00:08:42,021 --> 00:08:45,758 Major deficiencies are usually those that can impact 147 00:08:45,758 --> 00:08:48,060 the endpoints of the study, 148 00:08:48,995 --> 00:08:52,498 and if the site get many of those, 149 00:08:52,498 --> 00:08:57,737 it could put them at risk for continuing research in the future. 150 00:08:57,737 --> 00:09:01,641 So we really work towards educating and informing sites 151 00:09:01,641 --> 00:09:04,677 not to -- to do the best 152 00:09:04,677 --> 00:09:07,747 that they can to build their programs 153 00:09:07,747 --> 00:09:12,084 and develop their training systems so that doesn't happen. 154 00:09:12,084 --> 00:09:16,022 In final audit determinations are usually within three 155 00:09:16,022 --> 00:09:19,058 categories: acceptable, acceptable needs follow-up, or unacceptable. 156 00:09:19,058 --> 00:09:22,061 Acceptable there were very few deviations found. 157 00:09:22,061 --> 00:09:25,097 Acceptable needs follow-up there are probably some 158 00:09:25,097 --> 00:09:28,534 major deviations, not enough to be of concern. 159 00:09:28,534 --> 00:09:34,173 And if a site is doing much research, they will have some majors. 160 00:09:34,173 --> 00:09:35,474 It's just inevitable. 161 00:09:35,474 --> 00:09:39,779 It's difficult to be 100 percent correct at all times. 162 00:09:39,779 --> 00:09:44,083 Unacceptable, however, are findings related to lots of major deviations, 163 00:09:44,083 --> 00:09:48,854 a large percent of them compared to what would be expected. 164 00:09:48,854 --> 00:09:51,424 With those, depending on their severity, 165 00:09:52,291 --> 00:09:55,761 usually that requires a re-audit within a year. 166 00:09:55,761 --> 00:10:01,434 And if it's severely -- a severe problem, the sponsor may prohibit them 167 00:10:01,434 --> 00:10:05,371 from conducting future research for a time or forever. 168 00:10:05,371 --> 00:10:08,874 It really depends on the degree of complexity 169 00:10:08,874 --> 00:10:12,812 or degree of major issues that were found. 170 00:10:12,812 --> 00:10:16,282 So again, looking at the FDA inspection. 171 00:10:16,282 --> 00:10:18,484 The FDA will come in. 172 00:10:18,484 --> 00:10:22,855 They have a huge list of things that they like 173 00:10:22,855 --> 00:10:26,792 to look at and review during an FDA audit. 174 00:10:26,792 --> 00:10:30,596 And it is quite labor intensive and work for the research site. 175 00:10:30,596 --> 00:10:31,564 And they'll review 176 00:10:31,564 --> 00:10:36,035 and then they'll provide the site with what is called an FDA form 483. 177 00:10:36,035 --> 00:10:39,572 And you'll hear a site say, "What did your 483 say?" 178 00:10:39,572 --> 00:10:41,807 And this is what they're referring to. 179 00:10:41,807 --> 00:10:44,043 It basically provides a list of observations 180 00:10:44,043 --> 00:10:46,278 that the FDA found in the inspection. 181 00:10:46,278 --> 00:10:50,750 And the investigator then has to respond to this within a certain time frame. 182 00:10:50,750 --> 00:10:53,352 It's then reviewed at the FDA. 183 00:10:53,352 --> 00:10:58,658 The FDA makes a final determination and then it issues a response letter. 184 00:10:58,658 --> 00:11:03,162 And that letter can be anything from not that many issues, 185 00:11:03,162 --> 00:11:06,832 and they observed some basic compliance with pertinent regulations. 186 00:11:06,832 --> 00:11:10,836 They didn't -- basically didn't find many issues at all. 187 00:11:10,836 --> 00:11:16,242 To all the way up to a notice of initiation of disqualification proceedings 188 00:11:16,242 --> 00:11:20,746 and opportunity to explain where basically that site's been shut down. 189 00:11:20,746 --> 00:11:25,251 And they have the opportunity to appeal or to refute it, 190 00:11:25,251 --> 00:11:30,089 but it takes a lot of work and effort to get to that point. 191 00:11:30,089 --> 00:11:33,025 So they do carry a pretty heavy stick. 192 00:11:33,025 --> 00:11:36,996 So talk a little bit about adverse event reporting and monitoring. 193 00:11:36,996 --> 00:11:41,133 I had to throw this a little bit of a funny in. 194 00:11:41,133 --> 00:11:43,903 Basically, you know, adverse event reporting is important. 195 00:11:43,903 --> 00:11:47,039 It's a very vital piece to conducting clinical research. 196 00:11:48,374 --> 00:11:51,977 It's basically an adverse event is any untoward medical occurrence 197 00:11:51,977 --> 00:11:53,412 that may present itself 198 00:11:53,412 --> 00:11:56,682 during the treatment or administration with a pharmaceutical product 199 00:11:56,682 --> 00:12:01,353 and which may or may not have caused a relationship to the agent. 200 00:12:01,353 --> 00:12:02,788 So that's the event. 201 00:12:02,788 --> 00:12:07,126 A toxicity is an actual adverse event that does have causal relationship. 202 00:12:07,126 --> 00:12:10,362 It's basically the agent itself has caused the toxicity. 203 00:12:10,362 --> 00:12:13,599 For example, our EGFR agents cause a skin rash. 204 00:12:13,599 --> 00:12:16,736 We know a skin rash is a toxicity. 205 00:12:17,503 --> 00:12:20,239 There are serious adverse events, as well, 206 00:12:20,239 --> 00:12:23,375 or SAEs is the term you will hear. 207 00:12:23,375 --> 00:12:27,646 And this is basically any medical occurrence that at any dose 208 00:12:27,646 --> 00:12:31,951 results in death or a life-threatening event, requires -- an event 209 00:12:31,951 --> 00:12:35,855 that might require hospitalization, it may result in a disability, 210 00:12:35,855 --> 00:12:38,991 or incapacity, or congenital anomaly, or birth defects. 211 00:12:39,592 --> 00:12:42,294 All SAEs need to be reported. 212 00:12:42,294 --> 00:12:48,167 And they need to be reported as quickly as possible to the sponsor. 213 00:12:48,167 --> 00:12:52,204 And they also should be comply with regulatory requirements, 214 00:12:52,204 --> 00:12:57,409 which is to report them to regulatory authorities, including the IRB. 215 00:12:57,409 --> 00:12:59,445 So adverse event reporting. 216 00:12:59,445 --> 00:13:04,383 The NCI has common terminology criteria for adverse events, or CTCAE. 217 00:13:04,383 --> 00:13:07,987 Some of you are probably familiar with that. 218 00:13:08,721 --> 00:13:11,023 This is basically a rather 219 00:13:11,023 --> 00:13:16,595 large document now that allows -- lists multiple types of adverse events 220 00:13:16,595 --> 00:13:20,766 and then provides grading criteria to help you determine 221 00:13:20,766 --> 00:13:24,003 what severity that adverse event would be. 222 00:13:24,003 --> 00:13:29,575 It also helps to determine if the event was expected or unexpected. 223 00:13:29,575 --> 00:13:33,746 And it helps to then relate that information within 224 00:13:33,746 --> 00:13:37,449 -- is it related to the study intervention? 225 00:13:37,449 --> 00:13:42,555 There are ways that the information can be expedited and reported. 226 00:13:42,555 --> 00:13:48,561 The NCI now has city step errors or a common system that they use for their 227 00:13:48,561 --> 00:13:49,028 trials. 228 00:13:49,028 --> 00:13:53,365 That information is reported within the IRB sponsor 229 00:13:53,365 --> 00:13:57,303 and FDA also need to be included in the again, the 230 00:13:58,437 --> 00:14:00,840 reporting of the information. 231 00:14:00,840 --> 00:14:01,740 And this is just a quick The NCI now has CTEP-AERS, 232 00:14:01,740 --> 00:14:02,141 or a common system that they use for their trials. 233 00:14:02,141 --> 00:14:02,541 That information is reported within the IRBs, sponsor, and FDA 234 00:14:02,541 --> 00:14:03,075 also need to be included in the, again, the reporting of the information. 235 00:14:03,075 --> 00:14:03,509 And this is just a quick screen shot of kind of an older version right now. 236 00:14:03,509 --> 00:14:03,609 This is still version 4.0, but you can see where it lists the adverse 237 00:14:03,609 --> 00:14:03,742 event, and then provides the grading from one to four -- one to five. 238 00:14:03,742 --> 00:14:07,146 of of what kind of an older version right now this is still version 4.0, 239 00:14:07,813 --> 00:14:12,451 but you can see where it lists the adverse event and then pro 240 00:14:12,518 --> 00:14:16,422 for the grading of from one to four on one to five. 241 00:14:16,422 --> 00:14:20,326 Actually, five is almost always death as being the most severe. 242 00:14:20,326 --> 00:14:25,664 A point to make with the CTCAE it is a bit of an iterative process. 243 00:14:25,664 --> 00:14:28,868 The versions are changing on a fairly regular basis. 244 00:14:28,868 --> 00:14:33,138 So when you design your protocol, you want to indicate in it 245 00:14:33,138 --> 00:14:37,776 which version of the CTCAE are you expecting the research sites to use. 246 00:14:37,776 --> 00:14:41,313 And then be able to stick with that, as well. 247 00:14:41,313 --> 00:14:45,217 And as an FYI, they are looking and actually hopefully -- 248 00:14:45,217 --> 00:14:49,154 it's in a review process right now of a version 5.0. 249 00:14:49,154 --> 00:14:53,292 I don't think it's going to look a lot different from this, 250 00:14:53,525 --> 00:14:55,194 but it's in the works. 251 00:14:55,194 --> 00:14:57,329 So just be aware of that. 252 00:14:57,329 --> 00:15:00,966 Assigning attribution can be kind of challenging sometimes, particularly 253 00:15:00,966 --> 00:15:06,605 depending on the level of understanding and expertise at the CRA or nursing level. 254 00:15:06,605 --> 00:15:10,643 They range from unrelated up to definite, with the in-between 255 00:15:10,643 --> 00:15:12,678 being unlikely, possible, and probable. 256 00:15:12,678 --> 00:15:16,715 Unrelated and definite is sometimes pretty easy to figure out, 257 00:15:16,715 --> 00:15:20,352 but it's the levels in-between that might be challenging. 258 00:15:20,352 --> 00:15:24,523 And this is where I really encourage the investigator to be pulled in 259 00:15:24,523 --> 00:15:28,694 and help to make these decisions so the accurate information is provided. 260 00:15:28,694 --> 00:15:30,930 There are legal and regulatory issues. 261 00:15:30,930 --> 00:15:33,832 Again, I think going to get several of these. 262 00:15:33,832 --> 00:15:37,670 Other presentations you're going to have will cover these in more detail. 263 00:15:37,670 --> 00:15:40,572 But just to be aware that there are various 264 00:15:40,572 --> 00:15:43,776 regulatory agencies, and I'm going to provide you some slides 265 00:15:43,776 --> 00:15:47,947 that provide the actual links to these, but to be aware of them. 266 00:15:47,947 --> 00:15:50,182 to go in and check them out. 267 00:15:50,182 --> 00:15:52,418 There's a lot of information to learn. 268 00:15:53,352 --> 00:15:56,822 Regulatory documents are often based on the Belmont Report, 269 00:15:56,822 --> 00:15:58,724 which is an important document. 270 00:15:58,724 --> 00:16:01,060 There's a Code of Federal Regulations, 271 00:16:01,060 --> 00:16:04,897 which I've addressed and shared with you on previous slides. 272 00:16:04,897 --> 00:16:08,734 And then another really important document is the Internation Conference 273 00:16:08,734 --> 00:16:12,371 on Harmonization or the Good Clinical Practice Guidelines, GCP. 274 00:16:12,371 --> 00:16:17,576 As far as the Code of Federal Regulations, I tried to narrow down 275 00:16:17,576 --> 00:16:22,581 maybe some more specific ones to look at instead of trying to dig 276 00:16:22,581 --> 00:16:26,418 in through the entire code, which can be quite overwhelming. 277 00:16:26,418 --> 00:16:30,255 So I'll provide those for you here on this slide. 278 00:16:30,956 --> 00:16:35,027 And then the GCP is also a fairly large document, 279 00:16:35,027 --> 00:16:39,498 so I think if you can hone in on the section 280 00:16:39,498 --> 00:16:43,969 labeled E6, I provide the weblink here for you, as well. 281 00:16:43,969 --> 00:16:48,841 And the E6 goes through the basic principles of GCP, goes through 282 00:16:48,841 --> 00:16:51,276 trial management, safety reporting, quality assurance, 283 00:16:51,276 --> 00:16:54,546 and quality control, records, and reports, and monitoring. 284 00:16:54,546 --> 00:16:59,018 This is like the backbone of information provided to help sites 285 00:16:59,018 --> 00:17:02,287 be educated and understand, as well as investigators 286 00:17:02,287 --> 00:17:06,358 and researchers should all be very familiar with GCP guidelines.