Clinical trial cases

Enrolling patients who are likely to complete the trial NLP and machine learning to profile patients based on prior data on who is more likely to complete a trial, reducing drop-outs. Adapt site visit schedule if possible. Minimize out-of-pocket expenses Systematic review of all patient costs to identify opportunities to minimize impacts.

Increase likelihood of feeling respected Sentiment analysis and other NLP tools applied to all documents provided to patients. Prompts to interacting staff for personalizing interactions. Tailored messaging to participants to increase likelihood of retention.

Poor trial execution Automating reporting of events Automated prompting of events for patients and staff, reporting requirements, notes missed events, prompts for required reporting, including protocol deviations and adverse events.

Overall Factor analysis to improve trade-offs based on budget and other constraints Multicriteria decision making based on Pareto analysis or single aggregated evaluation function Valuated State Space to quantify and illuminate trade-offs. Open in a separate window. Acknowledgments The author thanks E. References 1. Abraha I. Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiology study.

Alam H. Web page summarization for handheld devices: a natural language approach; pp. Audet L. Associations between nurse education and experience and the risk of mortality and adverse events in acute care hospitals: systematic review of observational studies.

Babbs C. Choosing inclusion criteria that minimize the time and cost of clinical trials. World J. Baquet C. Analysis of Maryland cancer patient participation in national cancer institute-supported cancer treatment clinical trials. Bennette C.

Predicting low accrual in the National Cancer Institute's cooperative group clinical trials. JNCI J. Cancer Inst. Berg B. Optimal booking and scheduling in outpatient procedure centers. Op Res. Bernard D. National estimates of out-of-pocket health care expenditure burdens among nonelderly adults with cancer: to Bostock S. Association between low function health literacy and mortality in older adults: longitudinal cohort study. Bower P.

Improving recruitment to health research in primary care. Branke J. Automated design of production scheduling heuristics. IEEE Trans. Burke E. The state of the art of nurse rostering. Bryant J.

Payment to healthcare professionals for patient recruitment to trials: a systematic review. Byrne M. Participation in cancer clinical trials: why are patients not participating? Campbell M. Recruitment torandomised trials: strategies for trial enrollment and participation study: the STEPS study. Health Technol. Carlisle B. Unsuccessful trial accrual and human subjects protections: an empirical analysis of recently closed trials.

Carrell D. Challenges in adapting existing clinical natural language processing systems to multiple, diverse health care setttings. Cartmell K. Patient participation in cancer clinical trials: a pilot test of lay navigation.

Trials Comm. Chang B. Patient recruitment to a randomized clinical behavioral therapy for chronic heart failure. BMC Med. Chien C. An evolutionary approach to rehabilitation scheduling. A case study. Chin Feman S. Effectiveness of recruitment in clinical trials: an analysis of methods used in a trial for irritable bowel syndrome patients. Cohen D. Rosiglitazone: what went wrong? Covinsky K. The impact of serious illness on patients' families.

Study to understand prognoses and preferences for outcomes and risks of treatment. Crowther M. Phase 4 research: what happens when the rubber meets the road?

ASH Education Book. Cryder C. Informative inducement: study payment as a signal of risk. Csimma C. Large clinical trials in musculoskeletal trauma: are they possible? Lessons learned from the international study of the use of rhBMP-2 in open tibial fractures. Bone Joint Surg. D'Agostino R. The slippery slope of surrogate outcomes. Trials Cardiovasc. Dansky K. Patient satisfaction with ambulatory healthcare services: waiting time and filling time.

Health Serv. Daugherty C. Perceptions of cancer patients and their physicians involved in phase 1 trials. Davis T. Informed consent for clinical trials: a comparative study of standard versus simplified forms. De Wit N. Participation and successful patient recruitment in primary care.

Demner-Fushman D. What can natural language processing do for clinical decision support? Dickson S. Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings.

DiMasi J. The cost of drug development. Donovan J. Who can best recruit to randomized trials? Edwards P. Methods to increase response to postal and electronic questionnaires. Cochrane Database Syst.

El-Sadr W. Financial incentives for linkage to care and viral suppression among HIV-positive patients. Fan W. The power of social media analysis. Feller S. Fletcher B.

Improving the recruitment activity of clinicians in randomised controlled trials: a systematic review. BMJ Open. Fouad M. Enrollment of patients with lung and colorectal cancers onto clinical trials.

Getz K. Predicting successful site performance. Characterizing the real cost of site regulatory compliance. Measuring the incidence, causes, and repercussions of protocol amendments. Drug Inf. Godskesen T. Hope for a cure and altruism are the main motives behind participation in phase 3 clinical trials.

Hadden K. Halpern S. The continuing unethical conduct of underpowered clinical trials. Heneghan C. Why clinical trial outcomes fail to translate into benefits for patients. Henon C. Patient-reported tolerability of adverse events in phase 1 trials. ESMO Open.

Hill N. Patients with pulmonary arterial hypertension in clinical trials. Who are they? Hjorth M. Physician's attitudes toward clinical trials and their relationship to patient accrual in a Nordic multicenter study on myeloma. Cost-effectiveness of methods in personalized medicine. Results of a decision-analytic model in patients with acute myeloid leukemia with normal karyotype.

Hripcsak G. Use of natural language processing to translate clinical information from a database of , chest radiographic reports. Hrobjartsson A. Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors. Hughes J. What trial participants need to be told about placebo effects to give informed consent: a survey to establish existing knowledge among patients with back pain.

Hui D. Attrition rates, reasons and predictive factors in supportive and pallative oncology clinical trials. Hurtado-Chong A. Improving site selection in clinical studies: a standardised, objective, multistep method and first experience results. Hwang T. Failure of investigational drugs in late-stage clinical development and publication of trial results.

If the comparator, choice of reporting to the manufacturer of the comparator or most common report to the health agency as an expedited report without notifying the other manufacturer. In general, all investigators and IRBs are informed. The sponsor shall ensure that all relevant information about suspected serious unexpected adverse reactions that are fatal or life-threatening is recorded and reported as soon as possible to the competent authorities in all the Member States concerned, and to the Ethics Committee, and in any case no later than seven days after knowledge by the sponsor of such a case, and that relevant follow-up information is subsequently communicated within an additional eight days.

All other suspected serious unexpected adverse reactions shall be reported to the competent authorities concerned and to the Ethics Committee concerned as soon as possible but within a maximum of 15 days of first knowledge by the sponsor.

The sponsor shall also inform all investigators who involved in trial. Unblinding means revealing the arm or some component of an arm to which an individual participant has been assigned. For the FDA, the blind should be broken and the case reported unblinded to FDA if it meets the expediting criteria serious, unexpected, possible relation to the study drug.

That is, if the company anticipates the need to break the blind frequently, a mechanism to keep the blind in place or to have very limited unblinding and safety analysis e. Companies should thus be very sure that the case must be unblinded for reporting purposes before unblinding. If blinded members of the team obtain access to information which could reveal the treatment allocation of any participants in the trial, this will be treated as a protocol deviation and a potentially serious breach of GCP.

The CI will be responsible for onward reporting if required. Details of the error and any corrective and preventative actions implemented will be documented in the TMF, and will be provided to the statistician at the time of final analysis for consideration as to whether inclusion in the clinical study report is required. There are different guidelines from authorities. For example FDA and also health Canada consider those cases to be submitted as clinical trials cases and ema GVP module 6 has guidelines for both solicited and unsolicited reporting guidelines of compassionate use cases.

Regulatory Reporting. New simplified treatment for severe hypoglycaemia. Processing and submission of case: Once sponsor receive the reports it will be sent to case receipt team of pharmacovigilance. If the SAR is considered unexpected, the following process for expedited unblinded SUSAR reporting will be followed: The designated individual responsible for unblinded safety reporting will follow the study-specific unblinding process to reveal the treatment allocation for the relevant participant note that this may be separate from the emergency unblinding procedure.

Case 5 The study involves the recruitment of research participants with disease X to receive either an investigational drug or a placebo. Yes, the participants are prospectively assigned to receive an intervention, the investigational drug or placebo.

Yes, the effect being evaluated, relief of symptoms, is a health-related outcome. Case 6 The study involves the recruitment of research participants with disease X to receive an investigational drug.

Yes, the effect being evaluated, disease progression, is a health-related outcome. Case 7a The study involves the recruitment of research participants with disease X to test an investigational in vitro diagnostic device IVD.

No, in this context the IVD would not be considered an intervention. The IVD is being used to test its ability to measure antibody levels, but not to test its effects on any health-related biomedical or behavioral outcomes.

This study is not a clinical trial. Case 7b The study involves the recruitment of research participants with disease X to be evaluated with an investigational in vitro diagnostic device IVD. Yes, the participants are prospectively assigned to an intervention, measurement of an antibody level, with the idea that knowledge of that antibody level might affect clinical management. Yes, the study is designed to evaluate how knowledge of the level of an antibody might inform treatment.

Yes, the effect being measured, how blood antibody levels inform treatment, is a health-related outcome. Case 8 Note: As of April 28, case 8 has been removed. Please cases 7, 46 for related examples. Case 9 The study involves the recruitment of healthy volunteers who will be randomized to different durations of sleep deprivation including no sleep deprivation as a control and who will have stress hormone levels measured.

Yes, the healthy volunteers are human participants. Yes, the participants are prospectively assigned to an intervention, different durations of sleep deprivation followed by a blood draw. Yes, the study is designed to measure the effect of different durations of sleep deprivation on stress hormone levels. Yes, the effect being evaluated, stress hormone levels, is a health-related biomedical outcome.

This is a basic experimental study involving humans. Case 10a The study involves the analysis of de-identified, stored blood samples and de-identified medical records of patients with disease X who were treated with an approved drug.

No, the study does not involve human participants because only de-identified samples and information are used.

Case 10b The study involves the analysis of identifiable, stored blood samples and identified medical records of patients with disease X who were treated with an approved drug.

Yes, patients are human participants because the blood and information are identifiable. No, secondary research with biospecimens or health information is not a clinical trial. Case 11 The study involves the recruitment of a healthy volunteers whose blood is drawn for genomic analysis.

No, sample collection blood draw is not an intervention in this context. Case 12 Physicians report that some patients being treated with drug A for disease X are also experiencing some improvement in a second condition, condition Y. No, participants are not prospectively assigned to receive an intervention as they are receiving drugs as part of their clinical care. The surveys are being used for measurement, not to modify a biomedical or behavioral outcome.

Case 13a The study involves the recruitment of patients with disease X who are receiving one of three standard therapies as part of their clinical care. No, there is no intervention. The therapies are prescribed as part of clinical care; they are not prospectively assigned for the purpose of the study. The study is observational. Case 13b The study involves the recruitment of research participants with disease X vs.

No, the measures needed to assess the outcomes are not interventions in this context, as the study is not intended to determine whether the measures modify a health-related biomedical or behavioral outcome. Case 14 The study involves the recruitment of healthy volunteers for a respiratory challenge study; participants are randomized to receive different combinations of allergens.

Yes, healthy volunteers are human participants. Yes, healthy volunteers are prospectively assigned to randomly selected combinations of allergens. Yes, the study is evaluating the effects of different combinations of allergens on the immune response in healthy individuals. Yes, the study evaluates the severity and mechanism of the immune reaction to allergens, which are health-related biomedical outcomes.

Yes, participants are prospectively assigned to receive the investigational drug. Yes, the study evaluates memory, and retention and recall of information in the context of AD. Case 16 The study involves the recruitment of individuals to receive a new behavioral intervention for sedentary behavior.

Yes, participants are prospectively assigned to receive a behavioral intervention. Yes, the study is evaluating the effects of the intervetion on mediators of behavior change.

Yes, the effect being evaluated, mediators of behavior change, are behavioral outcomes relevant to health. Case 17 The study involves the recruitment of patients with disease X to be evaluated with a new visual acuity task.

Yes, the participants are prospectively assigned to an intervention, the new visual acuity test. No, the study is designed to evaluate the ability of the new visual acuity test to measure visual acuity as compared to the gold standard Snellen Test, but not to modify visual acuity. Case 18 Note: As of April 28, case 18 has been removed. Please cases 40, 43, 44, 45 for related examples. Case 19 The study involves the recruitment of research participants with CHF who were hospitalized before or after implementation of the Medicare incentives to reduce re-hospitalizations.

No, the intervention incentives to reduce re-hospitalization were assigned by Medicare, not by the research study. Case 20 The study involves the recruitment of healthcare providers to assess the extent to which being provided with genomic sequence information about their patients informs their treatment of those patients towards improved outcomes. Yes, both the physicians and the patients are human participants.

Yes, physicians are prospectively assigned to receive genomic sequence information, which is the intervention. Yes, the study is designed to evaluate the effect of intervening with physicians, on the treatment they provide to their patients. Is the effect being evaluated a health-related, biomedical, or behavioral outcome? Yes, the effect being evaluated, the extent to which providing specific information to physicians informs the treatment of patients, is a health-related outcome.

Case 21 The study involves the recruitment of research participants with a behavioral condition to receive either an investigational behavioral intervention or a behavioral intervention in clinical use.

Yes, the participants are prospectively assigned to an intervention, either the investigational intervention or an intervention in clinical use. Yes, the study is designed to evaluate whether the investigational intervention is as effective as the standard intervention, at changing behavior. Case 23 The study involves the recruitment of physicians who will be randomly assigned to use a new app or an existing app, which cues directed interviewing techniques. Yes, both the physicians and the families are human participants.

Yes, physicians are prospectively assigned to use one of two apps, which are the interventions. Yes, the study is designed to evaluate the effect of intervening with physicians, on social service support referral for families. Yes, the effect being evaluated, the number of referrals, is a health-related outcome.

Case 27 The study involves the recruitment of parents to participate in focus groups to discuss topics related to parental self-efficacy and positive parenting behaviors. Yes, the parents are human participants. No, a focus group is not an intervention. Case 28 The study involves the recruitment of healthy volunteers to test a new behavioral intervention.

Yes, study participants are human participants. Yes, the participants are prospectively assigned to a behavioral intervention. Yes, the study is designed to evaluate the effect of the intervention on adherence, and quality of life. Yes, adherence and quality of life are health-related outcomes. Case 29 A study will test the feasibility a mobile phone app designed to increase physical activity.

Yes, sedentary individuals will be enrolled. The participants will interact with the app for a week. The study is only measuring the usability and acceptability of the app, and testing for bugs in the software. The effect on physical activity is NOT being measured. Case 30a The study involves the recruitment of healthy family members of patients hospitalized for disease X to test two CPR training strategies.

Yes, family members of patients are human participants. Yes, the participants are prospectively assigned to one of two CPR educational strategies. Yes, the study is designed to evaluate the effect of educational strategies on CPR skills. Yes, retention of CPR skills is a health-related behavioral outcome. Case 30b The study involves the recruitment of research participants in three different communities clusters to test three CPR training strategies.

Yes, the participants are prospectively assigned to receive one of three types of CPR training, which is the intervention. Yes, the study is designed to evaluate the effect of different CPR training strategies on patient survival rates post cardiac arrest.

Yes, out-of-hospital cardiac arrest survival is a health-related outcome. Case 31a A study involves the recruitment of school children to evaluate two different tools for monitoring food intake. Yes, children are human participants. No, in this context the monitoring methods would not be considered an intervention. The study is designed to test the accuracy of two monitoring methods, but not to test the effect on any health-related biomedical or behavioral outcomes.

Case 31b A study involves the recruitment of school children to evaluate two different tools for monitoring food intake. FDA seeks to ensure that people of different ages, races, ethnic groups, and genders are included in clinical trials. Clinical trials can be sponsored by organizations such as a pharmaceutical company , Federal offices and agencies such as the National Institutes of Health or the U. Department of Veterans Affairs , or individuals such as doctors or health care providers.

The sponsor determines the location s of the trials, which are usually conducted at universities, medical centers, clinics, hospitals, and other Federally or industry-funded research sites. FDA works to protect participants in clinical trials and to ensure that people have reliable information before deciding whether to join a clinical trial.

The Federal government has regulations and guidelines for clinical research to protect participants from unreasonable risks. Although efforts are made to control the risks to participants, some may be unavoidable because we are still learning more about the medical treatments in the study. The government requires researchers to give prospective participants complete and accurate information about what will happen during the trial. Before joining a particular study, you will be given an informed consent document that describes your rights as a participant, as well as details about the study, including potential risks.

Signing it indicates that you understand that the trial is research and that you may leave at any time. The informed consent is part of the process that makes sure you understand the known risks associated with the study. Before joining a clinical trial, it is important to learn as much as possible.