Patient perspective : choosing or developing instruments

Previous Outcome Measures in Rheumatology (OMERACT) meetings recognized that patients view outcomes of intervention from a different perspective. This preconference position paper briefly sets out 2 patient-reported outcome (PRO) instrument approaches, the PROMISE computer adaptive testing (CAT) system and development of a rheumatoid arthritis-specific questionnaire to measure fatigue; a tentative proposal for a PRO instrument development pathway is also made.

Patient perspective workshop : moving towards OMERACT guidelines for choosing or developing instruments to measure patient-reported outcomes

The workshop Choosing or Developing Instruments held at the Outcome Measures in Rheumatology (OMERACT) 10 meeting was designed to help participants think about the underlying methods of instrument development. Conference pre-reading material and 3 brief introductory presentations elaborated the issues, and participants broke into discussion groups before reconvening to share insights, engage in a more general discussion of the issues, and vote on recommendations. Trade offs between using current imperfect measures and the long and complex process of developing new instruments were considered, together with the need for rigor in patient-reported outcome (PRO) instrument development. The main considerations for PRO instrument development were listed and a research agenda for action produced. As part of the agenda for action, it is recommended that researchers and patient partners work together to tackle these issues, and that OMERACT bring forward proposals for acceptable instrument development protocols that would meet an enhanced “Truth” statement in the OMERACT Filter.

Effectiveness of vertebroplasty using individual patient data from two randomised placebo controlled trials : meta-analysis

Objective To determine whether vertebroplasty is more effective than placebo for patients with pain of recent onset (≤6 weeks) or severe pain (score ≥8 on 0-10 numerical rating scale).

Design Meta-analysis of combined individual patient level data.

Setting Two multicentred randomised controlled trials of vertebroplasty; one based in Australia, the other in the United States.

Participants 209 participants (Australian trial n=78, US trial n=131) with at least one radiographically confirmed vertebral compression fracture. 57 (27%) participants had pain of recent onset (vertebroplasty n=25, placebo n=32) and 99 (47%) had severe pain at baseline (vertebroplasty n=50, placebo n=49).

Intervention Percutaneous vertebroplasty versus a placebo procedure.

Main outcome measure Scores for pain (0-10 scale) and function (modified, 23 item Roland-Morris disability questionnaire) at one month.

Results For participants with pain of recent onset, between group differences in mean change scores at one month for pain and disability were 0.1 (95% confidence interval −1.4 to 1.6) and 0.2 (−3.0 to 3.4), respectively. For participants with severe pain at baseline, between group differences for pain and disability scores at one month were 0.3 (−0.8 to 1.5) and 1.4 (−1.2 to 3.9), respectively. At one month those in the vertebroplasty group were more likely to be using opioids.

Conclusions Individual patient data meta-analysis from two blinded trials of vertebroplasty, powered for subgroup analyses, failed to show an advantage of vertebroplasty over placebo for participants with recent onset fracture or severe pain. These results do not support the hypothesis that selected subgroups would benefit from vertebroplasty.

Isolation of a novel Orientia species (O. chuto sp. nov.) from a patient infected in Dubai

In July 2006, an Australian tourist returning from Dubai, in the United Arab Emirates (UAE), developed acute scrub typhus. Her signs and symptoms included fever, myalgia, headache, rash, and eschar. Orientia tsutsugamushi serology demonstrated a 4-fold rise in antibody titers in paired serum collections (1:512 to 1:8,192), with the sera reacting strongest against the Gilliam strain antigen. An Orientia species was isolated by the in vitro culture of the patient's acute blood taken prior to antibiotic treatment. The gene sequencing of the 16S rRNA gene (rrs), partial 56-kDa gene, and the full open reading frame 47-kDa gene was performed, and comparisons of this new Orientia sp. isolate to previously characterized strains demonstrated significant sequence diversity. The closest homology to the rrs sequence of the new Orientia sp. isolate was with three strains of O. tsutsugamushi (Ikeda, Kato, and Karp), with a nucleotide sequence similarity of 98.5%. The closest homology to the 47-kDa gene sequence was with O. tsutsugamushi strain Gilliam, with a nucleotide similarity of 82.3%, while the closest homology to the 56-kDa gene sequence was with O. tsutsugamushi strain TA686, with a nucleotide similarity of 53.1%. The molecular divergence and geographically unique origin lead us to believe that this organism should be considered a novel species. Therefore, we have proposed the name “Orientia chuto,” and the prototype strain of this species is strain Dubai, named after the location in which the patient was infected.

Web health portal to enhance patient safety in Australian healthcare systems

The use of a web Health Portal can be employed not only for reducing health costs but also to view patient's latest medical information (e.g. clinical tests, pathology and radiology results, discharge summaries, prescription renewals, referrals, appointments) in real-time and carry out physician messaging to enhance the information exchanged, managed and shared in the Australian healthcare sector. The Health Portal connects all stakeholders (such as patients and their families, health professionals, care providers, and health regulators) to establish coordination, collaboration and a shared care approach between them to improve overall patient care safety. The paper outlines a Health Portal model for designing a real-time health prevention system. An application of the architecture is described in the area of web Health Portal.

Randomised controlled trials and 'unexpected' adverse events associated with newly released drugs : improvements in pharmacovigilance systems are necessary for real-time identification of patient safety risks

Adverse drug events are one of the major causes of morbidity in developed countries, yet the drugs involved in these events have been trialled and approved on the basis of randomised controlled trials (RCTs), regarded as the study design that will produce the best evidence.

Though the focus on adverse drug events has been primarily on processes and outcomes associated with the use of these approved drugs, attention needs to be directed to the way in which the RCT study design is structured. The implementation of controls to achieve internal validity in RCTs may be the very controls that reduce external validity, and contribute to the levels of adverse drug events associated with the release of a new drug to the wider patient population.

An examination of these controls, and the effects they can have on patient safety, underscore the importance of knowing about how the clinical trials of a drug are undertaken, rather than relying only on the recorded outcomes.

As the majority of new drugs are likely to be prescribed to older patients who have one or more comorbidities in addition to that targeted by a new drug, and as the RCTs of those drugs typically under-represent the elderly and exclude patients with multiple comorbidities, timely assessment of drug safety signals is essential.

It is unlikely that regulatory jurisdictions will undertake a reassessment of safety issues for drugs that are already approved. Instead, reliance has been placed on adverse drug event reporting systems. Such systems have a very low reporting rate, and most adverse drug events remain unreported, to the eventual cost to patients and healthcare systems.

This makes it essential for near real-time systems that can pick up safety signals as they occur, so that modifications to the product information (or removal of the drug) can be implemented.

Patient-reported outcomes in trials of incretin-based therapies in patients with type 2 diabetes mellitus

Incretin-based therapies have a glucose-dependent mode of action that results in excellent glucose-lowering efficacy with very low risk of hypoglycaemia, and weight neutrality [dipeptidyl peptidase-4 (DPP-4) inhibitors] or weight loss [glucagon-like peptide-1 (GLP-1) receptor agonists], in people with type 2 diabetes mellitus (T2DM). Patient-reported outcomes (PROs) complement physician evaluations of efficacy and tolerability and offer insights into the subjective experience of using modern diabetes treatments. We conducted a systematic search of clinical trials of the GLP-1 receptor agonists liraglutide, exenatide and long-acting exenatide, one of which included the oral DPP-4 inhibitor sitagliptin as a comparator. No other PRO data for DPP-4 inhibitors were identified. This review summarizes PRO data from eight clinical trials, the majority of which used the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and/or Impact of Weight on Quality of Life-Lite (IWQOL-Lite) to evaluate patient experience. People with T2DM were highly satisfied with modern incretin-based therapies compared with traditional therapies. Treatment satisfaction (including perceptions of convenience and flexibility) was high and generally higher with GLP-1 agonists in association with their greater glucose-lowering efficacy and tendency to facilitate weight loss. Weight-related quality of life (QoL) also improved in people using incretin therapies. The glycaemic improvements achieved with GLP-1 receptor agonists, coupled with the low incidence of hypoglycaemia and ability to cause weight loss, seemed to offset potential concern about injections. It is plausible that superior patient-reported benefits found in clinical trials may translate into improved, clinically meaningful, long-term outcomes through increased treatment acceptability. Long-term, prospective data are needed to ascertain whether this is the case in practice.

Patient and practitioner compliance with silicone hydrogel and daily disposable lens replacement in the United States

Objective: The objectives of this study were to assess current recommendations for replacement frequency (RF) of silicone hydrogel (SH) and daily disposable (DD) lenses, to determine compliance with these recommendations, and to investigate the reasons given for noncompliance.

Methods: A package containing 20 patient surveys was sent to 309 eye care practitioners (ECPs) in the United States who had agreed to participate in the study. One thousand eight hundred fifty-nine completed surveys were received from 158 ECPs and 1,654 surveys were eligible for analysis. Questions related to patient demographics, lens type, lens wearing patterns, the ECP instructions for RF, and the actual patient reported RF. ECPs were asked to provide lens information and their recommendation for RF after the surveys had been completed and sealed in envelopes. All responses were anonymous.

Results: Sixty-six percent of patients were women and their mean age was 34 ± 12 years. Eighty-eight percent of lenses were worn for daily wear, 12.8 ± 3.2 hours a day, 6.2 ± 1.5 days a week. Lens type distribution was 16% DD, 45% 2 week (2W) SH, and 39% 1 month (1M) SH. ECP recommendations for RF varied according to the lens type; 1% of 1M (95% CI 0.2-1.7), 4% of DD (95% CI 2.1-7.2), and 18% of 2W (95% CI 15.1-20.7) patients were given instructions that did not conform to the manufacturers' recommended RF (MRRF). When considering only those patients who were given the correct instructions for RF, 38% were not compliant with the MRRF; noncompliance rates varied according to the lens type and were 12% for DD (95% CI 8.6-17.2), 28% for 1M (95% CI 24.9-32.1), and 52% for 2W (95% CI 47.8-55.8). The most frequent reasons for over wearing lenses were forgetting which day to replace lenses (51%) and to save money (26%). Fifty-three percent believed that a reminder system would aid compliance; the most popular methods being a cell phone reminder or text message (29%) and a nominated day each week or month (26%). Discussions between the ECPs and the patients were more extensive for patients who were compliant with the MRRF.

Conclusions: ECPs recommended RFs more frequently with DD and 1M SH lenses than with 2W SH lenses, consistent with manufacturers' recommendations. Patients were less compliant with RF than ECPs for all lens types investigated. Patients were most compliant with RF when wearing DD lenses and least compliant when wearing 2W SH lenses. Better communication facilitated greater compliance with RF. More than half of those not replacing lenses, when recommended, reported that this was because they forgot which day to replace their lenses.

Patient use of smartphones to communicate subjective data in clinical trials

Purpose. Various methods have been used in clinical trials to collect time-sensitive subjective responses, including study diaries, telephone interviews, and use of text messaging. However, all of these methods are limited by the uncertainty of when the participants enrolled in the study actually record their responses. This technical note reports on the utility of the BlackBerry smartphone to collect such data and why such a system provides advantages over other methods to report subjective ratings in clinical studies.

Methods. The Centre for Contact Lens Research developed an on-line web-enabled system that permits participants to record and immediately transmit subjective rating scores in numerical form directly into a web-enabled database. This, combined with the utility of BlackBerrys, enabled time-specific e-mail requests to be sent to the study participants and then for that data to be simultaneously transmitted to the web-enabled database. This system has been used in several clinical trials conducted at the Centre for Contact Lens Research, in which data were collected at various times and in several specific locations or environments.

Results. In the clinical trials conducted using this system, participants provided responses on 97.5% of occasions to the requests for data generated by the automated system. When the request was for data on a set date, this method resulted in responses of 84.1% of the time.

Conclusions. The series of clinical trials reported here show the benefits of the utilization of the BlackBerry to collect time- or environment-sensitive data via a web-enabled system.