FDA Clinical TrialS Guidelines and Five Updaterevisions during the COVID-19 pandemic.

In response to a century-old pandemic, in addition to the need for hospitals to reconfigure and adjust their power, there are numerous measures related to curbing the global spread of COVID-19, including maintaining social distance, which inevitably affects the development of new drugs and other pharmaceutical productsPublic health and drug regulators recognize that the risk of exposure to or infection of COVID-19 in clinical trial sites, travel restrictions, disruption of the drug supply chain, and exposure to or infection of subjects and medical personnel can lead to difficulties in meeting specific processes set out in clinical and human trial protocolsDespite the disruption, there can be no compromise under any circumstances with regard to the strict requirements for ensuring the integrity and safety of drug developmentTo maintain the integrity of clinical trials and minimize the costs of indefinite lysizing on clinical trials, the FDA has issued guidelines to support the exploration of important research and new therapiesIn addition, the Office of Human Research and Conservation (OHRP) of the Department of Health and Human Services (HHS) has issued guidelines to help researchers properly apply human subject protection regulationsThe new guidelines and revisions issued in the COVID-19 pandemic, while meeting the social distance, mitigate the disruption of clinical trials and require compliance with the compliance criteria set out in the research programmeIn response to these exceptional circumstances, the FDA has issued and revised guidelines several times to assist sponsors and researchers in ensuring the integrity of clinical trials and the safety of clinical trial participants during the COVID-19 pandemicFDA Guidelines for Conducting Clinical Trials During the COVID-19 Pandemic March 18, 2020 The FDA issued the Guidelines for Clinical Trials of Pharmaceutical Products during the COVID-19 Public Health Emergency Period (hereafter referred to as the FDA Guidelines)This guidance for industry, research, and ethical review boards (IRB) provides specific guidance to the bidders to minimize the risks to the integrity of clinical trials during the COVID-19 pandemic while ensuring the safety of subjects and complying with the Pharmaceutical Clinical Trials Quality Management Practice (GCP)In accordance with FDA guidelines, it is recommended that the bidder consult with the researchers and the Ethics Review Committee (IRB) to determine whether they can continue to participate in the trial to maximize the safety of participantsSince participants may not be able to travel to the research site to complete the consultations provided for in the clinical trial scenario, the sponsor may consider alternatives that ensure safe diagnosis, such as telephone contact, virtual access, etcFor COVID-19 screening procedures enforced by the healthcare system, there is no need to report in programme revisions, except for situations where relevant data are required to be collected as part of a new study objectiveIn accordance with the guidelines issued by the FDA, in order to eliminate direct harm or protect the lives of research participants, if the pilot protocol must be changed, the initiator may make changes before IRB approval, or before the IRB approves the application for a clinical trial of a new drug or device (IND or IDE application), but must report the change afterwardsThe applicant must state in the case report form the basis for the lack of information due to changes in the way the study is treated, or by the discontinuation of the patient's medication, and for reasons related to the COVID-19 pandemicIf changes need to be made to the efficacy evaluation, the FDA recommends that the applicant consult with the appropriate review department to discuss changes to the data collection scheme for the endpoint of the efficacy, for example, to a virtual evaluation, or to postpone the evaluationFinally, if the policies and processes are not in place, the FDA recommends that the organizer develop policies and procedures to protect participants in the trial during the pandemicFor all clinical trials affected by the COVID-19 pandemic, the FDA requires the sponsor to indicate in its clinical study report the contingency measures taken for studies interrupted by the relevant response, to list all participants affected by the outage, and to analyze and discuss the impact of responses to the COVID-19 pandemic on the safety and effectiveness of the study results In accordance with 21 CFR 312.30(b) and 21 CFR 812.35 (a), amendments to the relevant act may be required as policies and processes change Five follow-up revisions to the FDA guidelines, first revised March 27, 2020, the FDA updated the guidelines to provide the first time in the relevant guidelines appendix, affected by the COVID-19 outbreak, more specific information about the challenges faced by clinical trials, such as how to ensure patient safety, how to obtain informed consent from isolated patients, etc The annex to the guide, updated on 27 March, contains 10 questions and answers This was followed by more timely iteration updates in the revisions to the guidelines issued on 16 April, 11 May and 14 May, bringing the total number of questions and answers to 22 On April 16th, the second revision of the new question and answer on 16 April focused on how to help the bidders in the event of limited electronic and remote functionality For example, if a researcher is not able to obtain an electronic version of informed consent, it will be possible to conduct informed interviews by fax, e-mail documentation, or over the phone It is considered appropriate, with due consideration in advance, through remote execution and interview-based outcome evaluation, as well as remote monitoring of the relevant test sites According to the updated guidelines, if the applicant encounters technical difficulties and has consulted the FDA for electronic submission, the applicant may request an exemption from eCTD within a limited time limit According to the updated appendix, commercially available drugs are permitted where the subject is unable to obtain the drug from the test site, but the product has been approved by the FDA for use in other indications In such cases, the applicant shall reimburse the subject for the purchase of commercially available medicines The third revision on May 11th was a new question-and-answer session on May 11th, covering alternative laboratories or imaging centers, as well as the use of video conferencing and post-marketing requirements (post-marketing requirements, PMR) The suitability of the relevant alternative institution for the use of data provided by an alternative laboratory or imaging center depends on whether the specific process escher in the clinical trial scenario is relevant to qualification criteria, safety evaluation, or endpoint evaluation In other words, if a laboratory test or imaging test is performed to evaluate safety, alternative agencies can be used as long as they follow the usual procedures, such as blood routines, chest X-rays, etc However, if the results of laboratory tests or imaging evaluations are used as a basis for a formal hypothesis test, the applicant shall consult the review department as to the applicability of the alternative agency Similarly, baseline testing should be discussed with the review authorities on the use of alternative laboratories or imaging centres to characterize the population subjects All alternative laboratories conducting testing should be certified by the Clinical Laboratory Improvement Amendments (CLIA) and comply with other requirements under the Act In addition, when using video conferencing for remote tours, the FDA recommends that the organizers consider training researchers or researchers to ensure that procedures to protect the privacy of subjects are in place and require that the identities of the researchers and participants in the trial be identified before participating in video conferencing The appendix to the new revised guide states that interaction through videoconferencing is not considered electronic records and therefore not subject to 21 CFR Part 11 for electronic records and electronic signatures The updated appendix also notes that FDA guidelines apply to all clinical trials, including those required for post-marketing requirements (PMR) If the sponsor anticipates that a related issue caused by COVID-19 will cause a delay in the expiration date required for a clinical trial of a drug or biological product, the FDA should encourage the sponsor to immediately notify the FDA of a feasible revised node for use in the interim, clinical trial completion, and final report submission Similarly, applicants should be encouraged to contact the FDA and propose revised nodes if there is an expected delay in the completion of post-market device research nodes In communicating with each other about possible delays, the bidder should provide instructions on how COVID-19 affects the ability to reach the node initially set Fourth Amendment, May 14Th, In an update released on May 14, the FDA provides recommendations for the Serious Adverse Events (SAEs) report The FDA stresses that if SAEs are an accident, but there is a reasonable possibility that SAEs will be associated with drug research, they should report SAEs If an unexpected SAEs occur during a clinical trial of an approved drug under study under the IND application, and the sponsor determines that SAEs are related to the drug under test, the relevant SAEs must be reported in the IND Safety Report If SAEs occur during clinical practice or during clinical trials and indicate the potential for new serious risks associated with it, an IND safety report should be submitted To assess whether there is a causal relationship between coVID-19 complications and the drug under test, the FDA recommended that the applicant compare the incidence of SAE among participants in the trial group infected with COVID-19, compared with the incidence of SAE observed in the control group or in the external population The fifth revision of the guidelines, issued on 3 June this year, on 3 June this year, supplements the description of obtaining informed consent for electronic signatures and conducting remote evaluations during clinical trials The FDA recognizes that program deviations can be unavoidable due to changes that occur after a pandemic As a result, the guide adds a new question-and-answer program to compliance with the electronically signed clinical trial recording electronic system 21 CFR Part 11 The newly revised question-and-answer session specifically cites the FDA's COVID MyStudies application as an example of an acceptable electronic method for obtaining informed consent The app is now available for download on Android and Apple platforms The FDA does not certify that existing software systems meet federal regulations for electronic signatures, but vendors can provide information to bidders to assess compliance In the absence of an electronic signature system that meets the requirements of 21 CFR Part 11, other methods must be used to obtain the required signature, either with an ink pen signature, a stylus signature, or a hand-drawn electronic signature that can print out and save on a related document The revision of the guidelines has also added information on the Remote Clinical Outcome Evaluation (COA) question-and-answer session The FDA included four separate COA types in the update that can be operated remotely in clinical trials conducted in the context of the COVID-19 emergency The four TYPES OF COA include performance-based outcomes, interviews-based clinicians reporting outcomes, patient report outcomes, and observer report outcomes The guide recognizes that some bidders may be making personal evaluations of the participants in the trial, and that remote evaluation methods may be used for other trials for security reasons or local government guidelines and restrictions The guidelines say that in deciding whether to change its clinical trial programme to include remote clinical outcome evaluation (COAs), the bidder should evaluate a set of considerations that cover general and specificity General considerations, including the likelihood of increased variation in the data, the possession of applicable technologies, ensuring applicable documentation, audit trails, and the overall feasibility of a given assessment method For clinical research outcomes based on performance and interviews, the biddershould consider whether the remote evaluation method is appropriate for the evaluated clinical study outcome Researchers should receive appropriate training in remote evaluation management At the same time, the environment of clinical trial participants should be evaluated to ensure privacy protection, safety and suitability According to the newly revised guidelines, when some evaluations cannot be completed with remote contact, researchers should use documentation, and the sponsor should be in the clinical trial data set, reporting the evaluation portion that cannot be done remotely The biddershoulde to consider whether the information collected remotely is sufficient to reliably evaluate clinical outcomes and support the relevant studies to draw reliable and robust conclusions For patient reports and observer outcomes, the specific considerations listed in the new revised guidelines include the possibility of missing data when switching from face-to-face evaluations to remote evaluations It should also be noted whether the transition from paper or electronic outcome evaluation to oral management evaluation leads to bias In particular, the Guide states that data collected through oral management evaluation methods is not a substitute for the necessary security monitoring The guidelines indicate that, in order to minimize the bias that can result from the use of oral management in the evaluation process, the applicant should ensure that interviewers are trained and that pre-prepared interview scripts are used in interviews Bidders may also consider using automated virtual interviewers or trained neutral third-party interviewers to manage evaluations remotely OHRP Guidelines for the Research Industry The Department of Health and Human Services (HHS) Office of Human Research Protection (OHRP) issues guidelines for the broader health care research industry On April 8, 2020, OHRP issued the COVID-19 OHRP Guidelines (hereafter referred to as the OHRP Guidelines) to assist researchers in the rational application of human subject protection regulations during the COVID-19 pandemic (45 CFR Part 46) OhRP's guidelines are different from those issued by the FDA in terms of the target audience and focus The guidelines issued by OHRP emphasize public health and safety priorities for all medical researchers and by emphasizing the protection of human subjects Under the OHRP Guidelines, measures taken for clinical or public health reasons are not considered research protocols and do not require the approval of the Ethics Review Committee (IRB) prior to implementation For example, mandatory COVID-19 screening procedures for patients in the relevant hospitals do not require IRB review Similarly, the relevant agencies share screening results with public health agencies without the need for IRB approval The OHRP guidelines state that the human subject protection regulations in 45 CFR Part 46 provide flexibility for these situations to allow researchers to include some public health surveillance activities in their studies For example, under the authority of the Public Health Department, in the relevant cases, the researcher may carry out the collection and testing of information or biological specimens without prior IRB approval Similarly, if required by law, it must not prevent researchers from reporting to public health structures specific test results with individually identifiable information (e.g COVID-19 test results) Consistent with OHRP's commitment to public health and safety, the OHRP guidelines state that researchers can make changes to previously approved studies prior to IRB review and approval to ensure that any apparent or direct harm to subjects is eliminated OhRP guide to the realities we face.