Search

Measures of pain intensity (eg, numeric rating scales [NRS]) are widely used in clinical research and practice. While these measures have evidence for validity and reliability, poor standardization of instructions, and response options limits precision of pain assessment, allows for inconsistency in interpretation, and presents a challenge for comparison and aggregation of study results. Despite these pitfalls, the 0 to 10 NRS remains the most commonly used primary outcome measure in clinical trials of pain treatments and is the core measure recommended by regulatory agencies. The purpose of this study was to describe the first phase in the development of a pain intensity measure that is easily interpretable, psychometrically sound, and that adheres to FDA qualification processes. The Analgesic, Anesthetic, and Addiction Clinical Trial, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership conducted concept elicitation interviews (N = 44; 22 with acute pain; 22 with chronic pain) to understand the patient perspective on rating pain intensity and to identify actionable suggestions for improved clarity and meaningfulness of instructions, recall periods, and response options. This article summarizes interview findings, describes how patient input and FDA feedback informed preliminary candidate measures, and provides an overview of the FDA qualification process. PERSPECTIVE: Concept elicitation interviews informed the development of content-valid candidate measures of acute and chronic pain intensity for planned use in clinical trials of pain treatments, and comprise the initial stage in FDA clinical outcome assessment qualification. Measures will subsequently be evaluated through cognitive interviews and a series of psychometric studies.

Women with a history of a preterm birth (PTB) are at high risk for recurrence. Weekly 17-hydroxyprogestrone caproate (17-P) injections can reduce the risk of recurrence in women with prior spontaneous PTB. PTB occurs disproportionately in non-Hispanic black (NHB) women, and uptake and adherence to 17-P among NHB women are lower compared to women in other racial/ethnic groups. Evidence-based interventions to improve 17-P uptake and adherence that incorporate women's perceptions and preferences are needed. Our objective was to identify women's perspectives and preferences for interventions to promote uptake of and adherence to 17-P, particularly among NHB women. We conducted an exploratory sequential mixed methods study using focus group discussions (FGDs), a survey, and in-depth interviews (IDIs). We recruited women with a history of PTB who self-identified as NHB for the FGDs and IDIs. Survey participation was open to any woman with a history of PTB regardless of their race and ethnicity. Women could only participate in one of the three data collection activities. Transcripts from the qualitative focus groups and in-depth interviews were analyzed using applied thematic analysis. Descriptive statistics was used to analyze the quantitative survey. Eighty-two women participated in the study (FGDs [n = 7], surveys [n = 60], and IDIs [n = 15]). Suggested interventions were separated into two categories: (1) clinic-based interventions (i.e., interventions delivered during the clinical encounter) and (2) community-based interventions (i.e., interventions delivered outside of the clinical encounter). Clinic level interventions included improved clinic access and scheduling, same-day appointments, appointment reminders, making the clinic experience more comfortable for patients, and encouragement from providers. Interventions at the community level included increased 17-P awareness among support persons, employers, and community members and administration of 17-P outside the clinic setting. Our findings offer multiple potential interventions that could improve uptake of and adherence to 17-P for PTB prevention among NHB women. These proposed interventions have the potential to mitigate barriers to 17-P and narrow the disparity in PTB rates. Given the alarming and increasing rates of prematurity and PTB disparities, it is imperative to test, refine, and incorporate effective interventions into clinical practice. Our findings provide insights from patients that can help shape such interventions.

OBJECTIVE Underrepresented racial and ethnic minorities are disproportionately affected by systemic lupus erythematosus (SLE). Racial and ethnic minorities also have more severe SLE manifestations that require use of immunosuppressive medications, and often have lower rates of medication adherence. We aimed to explore barriers of adherence to SLE immunosuppressive medications among minority SLE patients. METHODS We conducted a qualitative descriptive study using in-depth interviews with a purposeful sample of 1) racial minority SLE patients taking oral immunosuppressants (methotrexate, azathioprine, or mycophenolate), and 2) lupus clinic providers and staff. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. We grouped themes using the Capability, Opportunity, Motivation, Behavior conceptual model. RESULTS We interviewed 12 SLE patients (4 adherent, 8 non-adherent) and 12 providers and staff. We identified Capability barriers to include external factors related to acquiring medications, specifically cost, pharmacy, and clinic related issues; Opportunity barriers to include external barriers to taking medications, specifically logistic and medication related issues; and Motivation factors to include intrinsic barriers, encompassing patients' knowledge, beliefs, attitudes, and physical and mental health. The most frequently described barriers were cost, side effects, busyness/forgetting, and lack of understanding, although barriers differed by patient and adherence level, with logistic and intrinsic barriers described predominantly by non-adherent patients and side effects described predominantly by adherent patients. CONCLUSION Our findings suggest that interventions may be most impactful if they are designed to facilitate logistics of taking medications and increase patients' motivation while allowing for personalization to address the individual differences in adherence barriers.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is revising ICH E6 Good Clinical Practice (GCP). The Clinical Trials Transformation Initiative (CTTI) initiated a project to identify and provide ICH with stakeholders’ priority areas and suggestions for revising ICH E6 GCP. We conducted a global online survey to identify areas of ICH E6 GCP that are and are not in need of revision. A total of 327 stakeholders completed the survey. Stakeholders represent many research roles and types of organizations, are employed in 39 countries, and conduct research in 153 countries. The ICH E6 GCP principles mentioned most often (range, 25%–29%) in need of revision were implementing systems that assure quality, providing medical care by qualified physicians/dentists, protecting confidentiality and privacy, obtaining informed consent, and documenting and storing information. The Investigator section (n = 244, 75%) and Sponsor section (n = 242, 74%) of ICH E6 GCP were identified as needing the most revision and the Investigator Brochure section (n = 166, 51%) as needing the least revision. The topic most frequently mentioned as needing revision is Monitoring (n = 146; 45%) in the Sponsor section. Although none of the principles or topics in ICH E6 GCP were identified as needing revision by the majority of stakeholders, a meaningful percentage of stakeholders identified areas that they believe need revision. These findings, which represent the views of a wide variety of stakeholders, may be useful to ICH for identifying where specifically to focus their revision efforts. CTTI provided the final report to ICH with the project findings for their consideration.

Background: Good clinical practice (GCP) training is the industry standard for ensuring the quality conduct of registrational clinical trials. However, concerns have been raised about whether the current structure and delivery of GCP training sufficiently prepares clinical investigators and their delegates to conduct clinical trials. Methods: We conducted qualitative semi-structured interviews with 13 clinical investigators and 10 research sponsors to 1) examine characteristics of the quality conduct of sponsored clinical trials, including critical tasks and concerns perceived as essential for trial quality, 2) identify key knowledge and skills required to perform critical tasks, and 3) identify gaps and redundancies in GCP training and areas of improvement to ensure the quality conduct of clinical trials. We used applied thematic analysis to analyze the data. Results: The top three tasks identified as critical for the quality conduct of clinical trials were obtaining informed consent, ensuring protocol compliance, and protecting participants’ health and safety. Respondents acknowledged that GCP principles address each of these critical tasks; however, they described many challenges and burdens of GCP training, including high training frequency and repetitive content. Respondents suggested moving beyond GCP training as a mere check-box activity by making it more effective, engaging, and interactive. They also emphasized that applying GCP principles in a real-world, skills-based environment would increase the relevance of GCP training to investigators and their delegates. Conclusion: Our findings indicate that although investigators and sponsors recognize that GCP training addresses critical tasks necessary to the quality conduct of clinical trials, they articulated the need for significant improvement in the design, content, and presentation of GCP training.

Key Points Question What information do key stakeholders want in informed consent forms for noninferiority clinical trials on hospital-acquired and/or ventilator-associated bacterial pneumonia, and how should such information be described? Findings In this Delphi study of 52 key stakeholders (patients at risk of pneumonia, caregivers, representatives of institutional review boards, investigators, and study coordinators), consensus was reached on how to describe reassurances on patient health and treatment, a rationale for advance consent and early enrollment, and noninferiority. Meaning Results of this study suggest that inclusion of information on these concepts in informed consent forms may help potential participants make informed decisions about participating in noninferiority trials of health care–associated pneumonia treatment., Importance Information to be included in advance informed consent forms for health care–associated pneumonia treatment trials remains to be determined. Objective To identify and determine how to describe information to be included in an advance informed consent form for an early-enrollment noninferiority hospital-acquired and/or ventilator-associated bacterial pneumonia (HABP/VABP) clinical trial. Design, Setting, and Participants A Delphi consensus process with stakeholders in HABP/VABP clinical trials was conducted using qualitative semistructured telephone interviews from June to August 2016, followed by 2 online surveys, the first from April to May 2017, and the second from September to October 2017. All stakeholders who participated in the interview were invited to participate in the first survey. Stakeholders who participated in the first survey were invited to participate in the second survey. Stakeholders were patients at risk of pneumonia, caregivers, representatives of institutional review boards, investigators, and study coordinators. Main Outcomes and Measures Description and consensus of information to be included in advance informed consent forms for early enrollment in noninferiority HABP/VABP clinical trials. Results Suggestions from 52 stakeholders about what key informed consent concepts to include and how to explain them were used to create 3 categories to be included in an advance consent form: (1) reassurances on patient health and treatment, (2) rationale for advance consent and early enrollment, and (3) an explanation of noninferiority. At the end of the Delphi process, at least 80% consensus was reached among the 40 stakeholders who participated in the second online survey on each of the statements to include in the proposed consent text. Throughout the process, however, describing and reaching consensus on statements about noninferiority was more problematic than the other categories. Conclusions and Relevance The stakeholders endorsed consent language to be used in combination with a strategy for enrolling patients at highest risk for pneumonia before infection onset. Data-driven consent language may help potential participants make informed decisions about their involvement in clinical research and improve enrollment rates, which are necessary to evaluate new treatments and improve patient care. The proposed consent language may be adapted for other trials using an early enrollment strategy and for noninferiority trials., This study uses a Delphi consensus process to identify information to be included in an advance informed consent form for an early-enrollment, noninferiority clinical trial of treatments for hospital-acquired and/or ventilator-associated bacterial pneumonia.

BACKGROUND The successful adoption of mobile technology for use in clinical trials relies on positive reception from key stakeholders, including clinical investigators; however, little information is known about the perspectives of investigators using mobile technologies in clinical trials. OBJECTIVE The aim of this study was to seek investigators’ insights on the advantages and challenges of mobile clinical trials (MCTs); site-level budgetary, training, and other support needs necessary to adequately prepare for and implement MCTs; and the advantages and disadvantages for trial participants using mobile technologies in clinical trials. METHODS Using a qualitative descriptive study design, we conducted in-depth interviews with investigators involved in the conduct of MCTs. Data were analyzed using applied thematic analysis. RESULTS We interviewed 12 investigators who represented a wide variety of clinical specialties and reported using a wide range of mobile technologies. Investigators most commonly cited 3 advantages of MCTs over traditional clinical trials: more streamlined study operations, remote data capture, and improvement in the quality of studies and data collected. Investigators also reported that MCTs can be designed around the convenience of trial participants, and individuals may be more willing to participate in MCTs because they can take part from their homes. In addition, investigators recognized that MCTs can also involve additional burden for participants and described that operational challenges, technology adoption barriers, uncertainties about data quality, and time burden made MCTs more challenging than traditional clinical trials. Investigators stressed that additional training and dedicated staff effort may be needed to select a particular technology for use in a trial, helping trial participants learn and use the technology, and for staff troubleshooting the technology. Investigators also expressed that sharing data collected in real time with investigators and trial participants is an important aspect of MCTs that warrants consideration and potentially additional training and education. CONCLUSIONS Investigator perspectives can inform the use of mobile technologies in future clinical trials by proactively identifying and addressing potential challenges. CLINICALTRIAL

The Clinical Trials Transformation Initiative (CTTI) Investigator Qualification Project addresses the need for a more efficient and effective means of identifying qualified clinical investigators and delegates. Selection of investigators and delegates who are qualified by training and experience to conduct clinical trials is essential to safeguarding protections for study participants and ensuring data quality and integrity. Sponsors generally document investigator qualification through training on the principles of good clinical practice (GCP), as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), adopted by regulatory authorities in the United States, Japan and the European Union. Although these GCP principles provide an important foundation for promoting the conduct of quality clinical trials, the industry standard "one-size-fits-all" GCP training may not fully prepare investigators and delegates for conducting quality clinical trials. Routine GCP training alone may not be sufficient to prepare an inexperienced member of a site team, while repeating such training is unlikely to enhance the qualifications of an experienced researcher. The CTTI project team used findings from qualitative research activities, as well as input from an expert meeting with multiple stakeholders, to identify gaps and redundancies in the current training of investigators and their delegates and recommend practical, action-based solutions. CTTI provides recommendations on how to implement a more efficient and effective means of preparedness and qualification of investigators and delegates, determining whether a site team is a good fit for a particular protocol, and improving the quality of clinical trial conduct.

Background The successful adoption of mobile technology for use in clinical trials relies on positive reception from key stakeholders, including clinical investigators; however, little information is known about the perspectives of investigators using mobile technologies in clinical trials. Objective The aim of this study was to seek investigators’ insights on the advantages and challenges of mobile clinical trials (MCTs); site-level budgetary, training, and other support needs necessary to adequately prepare for and implement MCTs; and the advantages and disadvantages for trial participants using mobile technologies in clinical trials. Methods Using a qualitative descriptive study design, we conducted in-depth interviews with investigators involved in the conduct of MCTs. Data were analyzed using applied thematic analysis. Results We interviewed 12 investigators who represented a wide variety of clinical specialties and reported using a wide range of mobile technologies. Investigators most commonly cited 3 advantages of MCTs over traditional clinical trials: more streamlined study operations, remote data capture, and improvement in the quality of studies and data collected. Investigators also reported that MCTs can be designed around the convenience of trial participants, and individuals may be more willing to participate in MCTs because they can take part from their homes. In addition, investigators recognized that MCTs can also involve additional burden for participants and described that operational challenges, technology adoption barriers, uncertainties about data quality, and time burden made MCTs more challenging than traditional clinical trials. Investigators stressed that additional training and dedicated staff effort may be needed to select a particular technology for use in a trial, helping trial participants learn and use the technology, and for staff troubleshooting the technology. Investigators also expressed that sharing data collected in real time with investigators and trial participants is an important aspect of MCTs that warrants consideration and potentially additional training and education. Conclusions Investigator perspectives can inform the use of mobile technologies in future clinical trials by proactively identifying and addressing potential challenges.

Key Points Question Is an early enrollment strategy using advance consent for research on health care–associated pneumonia acceptable to stakeholders? Findings In this qualitative study of 52 stakeholders (patients at risk for pneumonia, caregivers, study investigators and coordinators, and representatives of institutional review boards), patients and caregivers found approaching patients and monitoring their records before they acquire pneumonia to be acceptable, indicated that patients can understand consent information before diagnosis, and described preferences for opt-out and precedent autonomy procedures. Institutional review board representatives were supportive of the strategy, and investigators and study coordinators indicated it would not be burdensome. Meaning Results of the study suggest that an early enrollment strategy is acceptable to stakeholders and should be evaluated for effectiveness in increasing enrollment in registrational clinical trials., This qualitative study assesses the perceived acceptability of stakeholders (patients, caregivers, investigators) to an early enrollment strategy using advance consent to antibacterial clinical trials for treatment of hospital-associated and ventilator-acquired bacterial pneumonia., Importance Better treatment options are needed in life-threatening infections, including health care–associated pneumonia. Enrolling patients in antibacterial clinical trials before diagnosis may circumvent existing time-to-enrollment constraints. However, the acceptability of an early enrollment strategy using advance consent is unknown. Objective To assess the perceived acceptability of an early enrollment strategy for enrolling patients in an antibacterial clinical trial before a pneumonia diagnosis. Design, Setting, and Participants This qualitative, descriptive study used semistructured telephone interviews. Framed within a planned noninferiority pneumonia antibiotic trial, an early enrollment strategy was described and perceptions were assessed. Using this strategy, patients give consent to enroll before developing pneumonia, to be monitored by study staff, and to be randomly assigned a study antibiotic if pneumonia develops. All interviews were audiorecorded, transcribed verbatim, and analyzed using applied thematic analysis. Fifty-two key stakeholders from across the United States, including 18 patients at risk of pneumonia, 12 caregivers, 10 representatives of institutional review boards, 7 investigators, and 5 study coordinators, were interviewed from June 20 to August 19, 2016. Main Outcomes and Measures Perceived acceptability of the early enrollment strategy. Results Among the 52 stakeholders interviewed (ages 29-75 years; 14 women), patients and caregivers expressed no concerns about patients being approached about participation before developing pneumonia; however, some patients may experience anxiety on learning about their risk for pneumonia. No concerns with study staff accessing patients’ medical records were expressed. The clarity of consent information was important for understanding the study rather than having the condition under investigation. Among patients, caregivers, and institutional review board representatives, preferences varied regarding opt-out and precedent autonomy procedures. Nearly all patients would be willing to join a trial using the early enrollment strategy and caregivers would be willing to provide proxy consent. Institutional review board representatives were supportive of the strategy and made recommendations for the study protocol, primarily around informed consent. Investigators and study coordinators believed the strategy would not be burdensome and offered suggestions to ensure its feasibility. Conclusion and Relevance Results of the study suggest that the early enrollment strategy is acceptable. Future research should evaluate whether the strategy improves enrollment rates in registrational pneumonia trials and in trials of other acute infection syndromes with narrow enrollment windows and/or patients with transient decisional incapacity.

SummaryGlobally, unplanned pregnancies and sexually transmitted infections (STIs) persist as significant threats to women’s reproductive health. Barriers to the use of modern contraceptives by women might inhibit uptake of novel woman-controlled methods for preventing STIs/HIV. Use of modern contraceptives and perceptions and attitudes towards contraceptive use were investigated among women in Antananarivo, Madagascar, using qualitative research. The hypothetical acceptability of the diaphragm – a woman-controlled barrier contraceptive device that also holds promise of protecting against STIs/HIV – was assessed. Women consecutively seeking care for vaginal discharge at a public health clinic were recruited for participation in a semi-structured interview (SSI) or focus group discussion (FGD). Audiotaped SSIs and FGDs were transcribed, translated and coded for predetermined and emerging themes. Of 46 participating women, 70% reported occasional use of male condoms, mostly for preventing pregnancy during their fertile days. Although women could name effective contraceptive methods, only 14% reported using hormonal contraception. Three barriers to use of modern contraceptives emerged: gaps in knowledge about the range of available contraceptive methods; misinformation and negative perceptions about some methods; and concern about social opposition to contraceptive use, mainly from male partners. These results demonstrate the need for programmes in both family planning and STI prevention to improve women’s knowledge of modern contraceptives and methods to prevent STI and to dispel misinformation and negative perceptions of methods. In addition, involvement of men will probably be a critical component of increased uptake of woman-controlled pregnancy and STI/HIV prevention methods and improved health.

Women need more choices for protection from HIV and other sexually transmitted infections (STIs). We conducted a randomized 4-week study in Madagascar in preparation for a Phase III randomized controlled trial (RCT) of the diaphragm with a candidate microbicide for STI prevention. All participants completed quantitative surveys; half participated in a qualitative interview. We advised women to wear the diaphragm at all times except for daily cleaning (rather than inserting it before intercourse). The objective of this analysis was to determine whether women who followed this "continuous use" approach more often used the diaphragm for 100% of sex acts as compared with other women. If so, this would support advising continuous diaphragm use in the upcoming RCT. To meet our objective, we analyzed qualitative data thematically, developed a measure of continuous diaphragm use based on qualitative data, and used multiple regression to evaluate the measure's association with adherence to diaphragm use during 100% of sex acts. Women who wore the diaphragm continuously had 4 times higher odds of reporting diaphragm use during 100% of sex acts (OR: 4.6, 95% CI: 1.2, 24.0). If the diaphragm proves effective against STI, continuous use may help women achieve high levels of protection.

Background The study was conducted to investigate past and future pregnancy preferences and contraceptive need among Malagasy sex workers. Study Design We analyzed data on pregnancy and contraceptive use collected during the baseline visit of a randomized, prospective formative trial which assessed diaphragm and microbicide acceptability among sex workers. To be eligible, women could not be pregnant or planning pregnancy for the next 2 months. Results Women ( N =192) from four cities (Antananarivo, Antsiranana, Mahajanga and Toamasina) reported a median of 10 sex acts per week. Fifty-two percent reported a prior unwanted pregnancy, 45% at least one induced abortion and 86% that preventing future pregnancy was moderately to very important. During the last sex act, 24% used a hormonal method, 36% used a male condom, 2% used a traditional method and 38% used no method. Nearly 30% of participants reported that pregnancy prevention was moderately or very important but used no contraception at last sex; these women were categorized as having ���unmet need��� for contraception. In multivariable binomial regression analyses, factors associated with unmet need included low knowledge of contraceptive effectiveness [age- and site-adjusted prevalence ratio (PR): 2.1; 95% confidence interval (CI): 1.4���3.0] and low self-efficacy to negotiate condom use (age- and site-adjusted PR: 2.0; 95% CI: 1.4���3.0). Conclusions Among these women, prior unwanted pregnancy and induced abortion were common and preventing future pregnancy was important, yet gaps in contraceptive use were substantial. Contraceptive knowledge and self-efficacy should be improved to promote contraceptive use by sex workers.

Background Women's perceived control over condom use has been found to be an important determinant of actual condom use in some studies. However, many existing analyses used cross-sectional data and little quantitative information exists to characterize the relationships between perceived control and actual condom use among sex worker populations. Methods We assessed the association between measures of perceived condom use control and self-reported use of male condoms employing data from a longitudinal pilot study among 192 sex workers in Madagascar. Results In multivariable models, a lack of perceived control over condom use with a main partner and having a main partner ever refuse to use a condom when asked were both associated with an increased number of sex acts unprotected by condoms in the past week with a main partner (RR 1.86; 95% CI 1.21-2.85; RR 1.34; 95% CI 1.03-1.73, respectively). Conversely, no measure of condom use control was significantly associated with condom use with clients. Conclusion Perceived control over condom use was an important determinant of condom use with main partners, but not clients, among sex workers in Madagascar. Programs working with sex workers should reach out to main and commercial partners of sex workers to increase male condom use.