Advancing the Use of Mobile Technologies in Clinical Trials: Recommendations from the Clinical Trials Transformation Initiative.

Mobile technologies offer the potential to reduce the costs of conducting clinical trials by collecting high-quality information on health outcomes in real-world settings that are relevant to patients and clinicians. However, widespread use of mobile technologies in clinical trials has been impeded by their perceived challenges. To advance solutions to these challenges, the Clinical Trials Transformation Initiative (CTTI) has issued best practices and realistic approaches that clinical trial sponsors can now use. These include CTTI recommendations on technology selection; data collection, analysis, and interpretation; data management; protocol design and execution; and US Food and Drug Administration submission and inspection. The scientific principles underpinning the clinical trials enterprise continue to apply to studies using mobile technologies. These recommendations provide a framework for including mobile technologies in clinical trials that can lead to more efficient assessment of new therapies for patients.

The Food and Drug Administration and pragmatic clinical trials of marketed medical products.

Pragmatic clinical trials can help answer questions of comparative effectiveness for interventions routinely used in medical practice. Pragmatic clinical trials may examine outcomes of one or more marketed medical products, and they are heterogeneous in design and risk. The Food and Drug Administration is charged with protecting the rights, safety, and welfare of individuals enrolled in clinical investigations, as well as assuring the integrity of the data upon which approval of medical products is made. The Food and Drug Administration has broad jurisdiction over drugs and medical devices (whether or not they are approved for marketing), and as such, clinical investigations of these products are subject to applicable Food and Drug Administration regulations. While many pragmatic clinical trials will meet the criteria for an exemption from the requirements for an investigational new drug application or investigational device exemption, in general, all clinical investigations of medical products that fall under Food and Drug Administration jurisdiction must adhere to regulations for informed consent and review by an institutional review board. We are concerned that current Food and Drug Administration requirements for obtaining individual informed consent may deter or delay the conduct of pragmatic clinical trials intended to develop reliable evidence of comparative safety and effectiveness of approved medical products that are regulated by the Food and Drug Administration. Under current regulations, there are no described mechanisms to alter or waive informed consent to make it less burdensome or more practicable for low-risk pragmatic clinical trials. We recommend that the Food and Drug Administration establish a risk-based approach to obtaining informed consent in pragmatic clinical trials that would facilitate the conduct of pragmatic clinical trials without compromising the protection of enrolled individuals or the integrity of the resulting data.

Oral contraceptive use for the primary prevention of ovarian cancer.

OBJECTIVE: To estimate the overall balance of harms and benefits from the potential use of oral contraceptives (OCs) for the primary prevention of ovarian cancer DATA SOURCES: We searched PubMed®, Embase®, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for English-language studies published from January 1990 to June 2012 that evaluated the potential benefits (reduction in ovarian, colorectal, and endometrial cancers) and harms (increase in breast and cervical cancer, and vascular complications) of OC use. REVIEW METHODS: Two investigators screened each abstract and full-text article for inclusion; the investigators abstracted data, and they performed quality ratings, applicability ratings, and evidence grading. Random-effects models were used to compute summary estimates of effects. A simulation model was used to estimate the effects of OC use on the overall balance of benefits and harms. RESULTS: We reviewed 55 studies relevant to ovarian cancer outcomes, 66 relevant to other cancers, and 50 relevant to vascular events. Ovarian cancer incidence was significantly reduced in OC users (OR [odds ratio], 0.73; 95% CI [confidence interval], 0.66 to 0.81), with greater reductions seen with longer duration of use. Breast cancer incidence was slightly but significantly increased in OC users (OR, 1.08; 95% CI, 1.00 to 1.17), with a significant reduction in risk as time since last use increased. The risk of cervical cancer was significantly increased in women with persistent human papillomavirus infection who used OCs, but heterogeneity prevented a formal meta-analysis. Incidences of both colorectal cancer (OR, 0.86; 95% CI, 0.79 to 0.95) and endometrial cancer (OR, 0.57; 95% CI, 0.43 to 0.76) were significantly reduced by OC use. The risk of vascular events was increased in current OC users compared with nonusers, although the increase in myocardial infarction was not statistically significant. The overall strength of evidence for ovarian cancer prevention was moderate to low, primarily because of the lack of randomized trials and inconsistent reporting of important characteristics of use, such as duration. The simulation model predicted that the combined increase in risk of breast and cervical cancers and vascular events was likely to be equivalent to or greater than the decreased risk in ovarian cancer, although the harm/benefit ratio was much more favorable when protection against endometrial and colorectal cancers was added, resulting in net gains in life expectancy of approximately 1 month. CONCLUSIONS: There is insufficient evidence to recommend for or against the use of OCs solely for the primary prevention of ovarian cancer. Although the net effects of the current patterns of OC use likely result in increased life expectancy when other noncontraceptive benefits are included, the harm/benefit ratio for ovarian cancer prevention alone is uncertain, particularly when the potential quality-of-life impact of breast cancer and vascular events are considered.

Enabling health care decisionmaking through clinical decision support and knowledge management.

OBJECTIVES: To catalogue study designs used to assess the clinical effectiveness of CDSSs and KMSs, to identify features that impact the success of CDSSs/KMSs, to document the impact of CDSSs/KMSs on outcomes, and to identify knowledge types that can be integrated into CDSSs/KMSs. DATA SOURCES: MEDLINE(®), CINAHL(®), PsycINFO(®), and Web of Science(®). REVIEW METHODS: We included studies published in English from January 1976 through December 2010. After screening titles and abstracts, full-text versions of articles were reviewed by two independent reviewers. Included articles were abstracted to evidence tables by two reviewers. Meta-analyses were performed for seven domains in which sufficient studies with common outcomes were included. RESULTS: We identified 15,176 articles, from which 323 articles describing 311 unique studies including 160 reports on 148 randomized control trials (RCTs) were selected for inclusion. RCTs comprised 47.5 percent of the comparative studies on CDSSs/KMSs. Both commercially and locally developed CDSSs effectively improved health care process measures related to performing preventive services (n = 25; OR 1.42, 95% confidence interval [CI] 1.27 to 1.58), ordering clinical studies (n = 20; OR 1.72, 95% CI 1.47 to 2.00), and prescribing therapies (n = 46; OR 1.57, 95% CI 1.35 to 1.82). Fourteen CDSS/KMS features were assessed for correlation with success of CDSSs/KMSs across all endpoints. Meta-analyses identified six new success features: Integration with charting or order entry system. Promotion of action rather than inaction. No need for additional clinician data entry. Justification of decision support via research evidence. Local user involvement. Provision of decision support results to patients as well as providers. Three previously identified success features were confirmed: Automatic provision of decision support as part of clinician workflow. Provision of decision support at time and location of decisionmaking. Provision of a recommendation, not just an assessment. Only 29 (19.6%) RCTs assessed the impact of CDSSs on clinical outcomes, 22 (14.9%) assessed costs, and 3 assessed KMSs on any outcomes. The primary source of knowledge used in CDSSs was derived from structured care protocols. CONCLUSIONS: Strong evidence shows that CDSSs/KMSs are effective in improving health care process measures across diverse settings using both commercially and locally developed systems. Evidence for the effectiveness of CDSSs on clinical outcomes and costs and KMSs on any outcomes is minimal. Nine features of CDSSs/KMSs that correlate with a successful impact of clinical decision support have been newly identified or confirmed.

Transitional care after hospitalization for acute stroke or myocardial infarction: a systematic review.

BACKGROUND: Transitional care is a time-limited service to prevent discontinuous care and adverse outcomes, including rehospitalization. PURPOSE: To describe transitional care interventions and evidence of benefit or harm in patients hospitalized for acute stroke or myocardial infarction (MI). DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Cochrane Database of Systematic Reviews, and EMBASE, supplemented with manual searches of reference lists of relevant studies and review articles (January 2000 to March 2012). STUDY SELECTION: 6 reviewers screened 5857 citations to identify English-language reports of trials or observational studies that compared transitional care with usual care among adults hospitalized for stroke or MI and that reported patient, caregiver, process, or systems outcomes within 1 year of hospital discharge. DATA EXTRACTION: Data on study design, quality, population, intervention characteristics, and patient- and system-level outcomes were extracted by 3 reviewers and confirmed by 1 additional reviewer. DATA SYNTHESIS: 62 articles representing 44 studies of transitional care for either acute stroke (27 studies) or MI (17 studies). Four intervention types were studied: hospital-initiated support (n = 14), patient and family education (n = 7), community-based support (n = 20), and chronic disease management (n = 3). Most studies (68%) were of fair quality. Overall, moderate-strength evidence showed that hospital-initiated support reduced length of stay for patients who had a stroke, and low-strength evidence showed that it reduced mortality for patients who had an MI. Evidence about benefits of other interventions and harms from transitional care services was insufficient. LIMITATIONS: Few studies had high-quality research designs. The usual care comparator was often poorly defined. Applicability to U.S. clinical practice was limited; only 6 studies were conducted in the United States. CONCLUSION: Available evidence shows that hospital-initiated transitional care can improve some outcomes in adults hospitalized for stroke or MI. Finding additional transitional care interventions that improve functional outcomes and prevent rehospitalizations and adverse events is a high priority for the growing population of patients who have an MI or a stroke. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Effect of clinical decision-support systems: a systematic review.

BACKGROUND: Despite increasing emphasis on the role of clinical decision-support systems (CDSSs) for improving care and reducing costs, evidence to support widespread use is lacking. PURPOSE: To evaluate the effect of CDSSs on clinical outcomes, health care processes, workload and efficiency, patient satisfaction, cost, and provider use and implementation. DATA SOURCES: MEDLINE, CINAHL, PsycINFO, and Web of Science through January 2011. STUDY SELECTION: Investigators independently screened reports to identify randomized trials published in English of electronic CDSSs that were implemented in clinical settings; used by providers to aid decision making at the point of care; and reported clinical, health care process, workload, relationship-centered, economic, or provider use outcomes. DATA EXTRACTION: Investigators extracted data about study design, participant characteristics, interventions, outcomes, and quality. DATA SYNTHESIS: 148 randomized, controlled trials were included. A total of 128 (86%) assessed health care process measures, 29 (20%) assessed clinical outcomes, and 22 (15%) measured costs. Both commercially and locally developed CDSSs improved health care process measures related to performing preventive services (n= 25; odds ratio [OR], 1.42 [95% CI, 1.27 to 1.58]), ordering clinical studies (n= 20; OR, 1.72 [CI, 1.47 to 2.00]), and prescribing therapies (n= 46; OR, 1.57 [CI, 1.35 to 1.82]). Few studies measured potential unintended consequences or adverse effects. LIMITATIONS: Studies were heterogeneous in interventions, populations, settings, and outcomes. Publication bias and selective reporting cannot be excluded. CONCLUSION: Both commercially and locally developed CDSSs are effective at improving health care process measures across diverse settings, but evidence for clinical, economic, workload, and efficiency outcomes remains sparse. This review expands knowledge in the field by demonstrating the benefits of CDSSs outside of experienced academic centers. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Transition of care for acute stroke and myocardial infarction patients: from hospitalization to rehabilitation, recovery, and secondary prevention.

OBJECTIVES: To review the available published literature to assess whether evidence supports a beneficial role for coordinated transition of care services for the postacute care of patients hospitalized with first or recurrent stroke or myocardial infarction (MI). This review was framed around five areas of investigation: (1) key components of transition of care services, (2) evidence for improvement in functional outcomes, morbidity, mortality, and quality of life, (3) associated risks or potential harms, (4) evidence for improvement in systems of care, and (5) evidence that benefits and harms vary by patient-based or system-based characteristics. DATA SOURCES: MEDLINE(®), CINAHL(®), Cochrane Database of Systematic Reviews, and Embase(®). REVIEW METHODS: We included studies published in English from 2000 to 2011 that specified postacute hospitalization transition of care services as well as prevention of recurrent stroke or MI. RESULTS: A total of 62 articles representing 44 studies were included for data abstraction. Transition of care interventions were grouped into four categories: (1) hospital -initiated support for discharge was the initial stage in the transition of care process, (2) patient and family education interventions were started during hospitalization but were continued at the community level, (3) community-based models of support followed hospital discharge, and (4) chronic disease management models of care assumed the responsibility for long-term care. Early supported discharge after stroke was associated with reduced total hospital length of stay without adverse effects on functional recovery, and specialty care after MI was associated with reduced mortality. Because of several methodological shortcomings, most studies did not consistently demonstrate that any specific intervention resulted in improved patient-or system -based outcomes. Some studies included more than one intervention, which made it difficult to determine the effect of individual components on clinical outcomes. There was inconsistency in the definition of what constituted a component of transition of care compared to "standard care." Standard care was poorly defined, and nearly all studies were underpowered to demonstrate a statistical benefit. The endpoints varied greatly from study to study. Nearly all the studies were single-site based, and most (26 of 44) were conducted in countries with national health care systems quite different from that of the U.S., therefore limiting their generalizability. CONCLUSIONS: Although a basis for the definition of transition of care exists, more consensus is needed on the definition of the interventions and the outcomes appropriate to those interventions. There was limited evidence that two components of hospital-initiated support for discharge (early supported discharge after stroke and specialty care followup after MI)were associated with beneficial effects. No other interventions had sufficient evidence of benefit based on the findings of this systematic review. The adoption of a standard set of definitions, a refinement in the methodology used to study transition of care, and appropriate selection of patient-centered and policy-relevant outcomes should be employed to draw valid conclusions pertaining to specific components of transition of care.