Development of a complex intervention improved randomization and informed consent in a randomized controlled trial

ObjectiveMulticenter randomized trials are required for pragmatic evaluations of health care interventions, but recruitment is difficult. Systematic reviews failed to identify robust strategies to improve recruitment. We developed and evaluated a complex intervention to increase levels of randomization and informed consent.Study Design and SettingThe ProtecT (Prostate testing for cancer and Treatment) trial compares radical surgery, radical conformal radiotherapy, and active monitoring for men aged 50–69 years with localized prostate cancer. The intervention was developed using qualitative research methods (content, thematic and conversation analysis). Rates of randomization and immediate acceptance of allocation were measured every 6 months to evaluate the impact of the intervention.ResultsThe complex intervention comprised reviews of centers falling below study targets, training programmes, documents and individually tailored feedback. Over 65% of eligible participants consented to randomization. Trial participants became increasingly well informed as immediate acceptance of allocation rose from 65% to 81% between 2001 and 2005.ConclusionThis complex intervention resulted in high levels of randomization and informed consent in a difficult trial. The generic aspects of the intervention could be applied to other trials to maximize randomization and informed consent, and allow the mounting of trials previously considered too difficult.     

A randomized controlled trial comparing three invitation strategies in a breast cancer screening program

BACKGROUND: The objective of this study was to compare the response received by a population-based breast cancer screening program, according to three different invitation strategies: letters sent by mail from the program (program group), letters sent by mail from the Primary Health Care Team (PHT group), and direct contact through a trained professional (direct contact group). METHODS: We used a cluster-randomized controlled trial with assignment to invitation group using home address. Nine hundred eighty-six women of Barcelona (Spain), ages 50 to 64 years, were invited to participate in the program. The main outcome used was the response rate after the first invitation. RESULTS: Five hundred sixty-four women accepted the invitation (57.2%). The highest response rate was achieved in the direct contact group (63.5%), followed by the PHT group (55.6%), the program group being the one that attained the lowest response rate (52.1%). The direct contact group had a higher probability of participating than the PHT group (RR = 1.14, P = 0.037) or the program group (RR = 1.22, P = 0.003). The response rate in the direct contact group was 72.1% when the letter was received by the subject herself. The increase in response occurred particularly among women of lower educational level. CONCLUSIONS: Inviting women to participate in a breast cancer screening program through direct contact by trained personnel increased participation rate compared with mailed-letter methods. The positive effect appeared restricted to women with lower educational levels.     

A multimedia consent tool for research participants in the Gambia: a randomized controlled trial

ObjectiveTo assess the effectiveness of a multimedia informed consent tool for adults participating in a clinical trial in the Gambia.MethodsAdults eligible for inclusion in a malaria treatment trial (n = 311) were randomized to receive information needed for informed consent using either a multimedia tool (intervention arm) or a standard procedure (control arm). A computerized, audio questionnaire was used to assess participants’ comprehension of informed consent. This was done immediately after consent had been obtained (at day 0) and at subsequent follow-up visits (days 7, 14, 21 and 28). The acceptability and ease of use of the multimedia tool were assessed in focus groups.FindingsOn day 0, the median comprehension score in the intervention arm was 64% compared with 40% in the control arm (P = 0.042). The difference remained significant at all follow-up visits. Poorer comprehension was independently associated with female sex (odds ratio, OR: 0.29; 95% confidence interval, CI: 0.12–0.70) and residing in Jahaly rather than Basse province (OR: 0.33; 95% CI: 0.13–0.82). There was no significant independent association with educational level. The risk that a participant’s comprehension score would drop to half of the initial value was lower in the intervention arm (hazard ratio 0.22, 95% CI: 0.16–0.31). Overall, 70% (42/60) of focus group participants from the intervention arm found the multimedia tool clear and easy to understand.ConclusionA multimedia informed consent tool significantly improved comprehension and retention of consent information by research participants with low levels of literacy.     

A randomized controlled trial of home telecare

We have established a randomized controlled trial of home telecare. The intervention aims to address a growing problem in the National Health Service (NHS), that is, high admission rates of patients with exacerbations of chronic obstructive pulmonary disease (COPD). Equipment procurement for the trial has been difficult, as no single supplier was able to meet the project s full requirements. The fact that the service is provided by existing clinical NHS staff has advantages when considering the generalizability of the results within the NHS. However, there are also disadvantages, since existing staff have little research experience. Considerable time has been required to help staff familiarize themselves with the equipment and become comfortable with its use. This has posed a barrier to the implementation of the service.     

Beyond informed consent

Although a relatively recent phenomenon, the role of informed consent in human research is central to its ethical regulation and conduct. However, guidelines often recommend procedures for obtaining informed consent (usually written consent) that are difficult to implement in developing countries. This paper reviews the guidelines for obtaining informed consent and also discusses prevailing views on current controversies, ambiguities and problems with these guidelines and suggests potential solutions. The emphasis in most externally sponsored research projects in developing countries is on laborious documentation of several mechanical aspects of the research process rather than on assuring true comprehension and voluntary participation. The onus for the oversight of this process is often left to overworked and ill-equipped local ethics review committees. Current guidelines and processes for obtaining informed consent should be reviewed with the specific aim of developing culturally appropriate methods of sharing information about the research project and obtaining and documenting consent that is truly informed. Further research is needed to examine the validity and user friendliness of innovations in information sharing procedures for obtaining consent in different cultural settings.     

A randomized controlled trial comparing three different techniques of nasojejunal feeding tube placement in critically ill children

BACKGROUND: The goal of this study was to compare 3 different techniques used to place nasojejunal (NJ) feeding tubes in the critically ill or injured pediatric patients. This was a randomized, prospective trial in a university-affiliated 12-bed pediatric intensive care unit. Patients were critically ill children requiring placement of an NJ feeding tube. Patient age, weight, medications, use of mechanical ventilation, and patient tolerance were recorded. An abdominal radiograph obtained immediately after the placement determined correct placement. The final placement was recorded, as was the number of placement attempts. METHODS: Patients were randomized to 1 of 3 groups: standard technique, standard technique facilitated with gastric insufflation, and standard technique facilitated with the use of preinsertion erythromycin. To ensure equal distribution, all patients were stratified by weight (<10 kg vs > or =10 kg) before randomization. All NJ tubes were placed by one of the investigators. If unsuccessful, a second attempt by the same investigator was allowed. Successful placement of the NJ tube was defined by confirmation of the tip of the tube in the first part of the duodenum or beyond by a pediatric radiologist blinded to the treatment groups. RESULTS: Seventy-five pediatric patients were enrolled in the study; 94.6% (71/75) of tubes were passed successfully into the small bowel on the first or second attempt. Evaluation of the data revealed no significant association with a specific technique and successful placement (p = .1999). CONCLUSIONS: When placed by a core group of experienced operators, the majority of NJ feeding tubes can be placed in critically ill or injured children on the first or second attempt, regardless of the technique used.     

The one-person randomized controlled trial

Currently, the gold standard for collection of clinical evidence is the randomized controlled trial (RCT), preferably with large, multicenter samples of subjects. Although this approach provides valuable information, many clinicians find it difficult to translate RCT results to the individual patient level. In this report, a statistical approach called Design of Experiments (DOE) is described as a method of applying the principles of RCTs one person at a time. An overview of the method, with a simple clinical example, is presented. As shown, DOE is a more efficient method than the sequential approach often taken by clinicians and their patients when evaluating various treatment choices. Further, the effect of multiple interventions can be assessed, alone or in combination with each other. In this way, DOE can be an important addition to the field of evidence-based medicine, although further studies are needed.     

Readability of informed consent

A comparative study has been made of the readability of informed consent form of the Navarra Health Service, using the Flesh and SMOG formulas. Signed editorial articles from the local newspapers Diario de Navarra and Diario de Noticias were used as a term of comparison. The results show that the readability of informed consent form is -4 (with a second paragraph of -9), while the editorial articles showed a comprehensibility of 22. The text of the second paragraph of the informed consent form is barely comprehensible, and alternative texts that are more easily comprehensible must be studied.     

An analysis of factors that predict patient consent to take part in a randomized controlled trial

BACKGROUND: Recruitment targets of patients to multi-centre primary care-based randomized controlled trials (RCT) are often not met. A critical step in the pathway is whether an eligible patient will give consent. OBJECTIVE: To assess whether patient, practice or practitioner characteristics are associated with a patient's likelihood of giving consent to participation in a large primary care-based RCT. METHODS: A cross-sectional study of patients from 260 practices in England and Wales who met the eligibility criteria for an RCT of aspirin versus warfarin for stroke prevention and attended an appointment with their GP to consider trial participation. Logistic regression analysis was used to determine which patient and practitioner factors independently predicted whether or not a patient would give consent to take part in the trial. RESULTS: Of the 1740 patients, 973 (55.9%) gave consent. On multivariable analysis, patient factors associated with increased likelihood of giving consent were younger age, current use of warfarin and year of recruitment to the trial. Patients with a history of transient ischaemic attack, angina or valve disease were less likely to give consent. Practice/practitioner factors that were associated with increased likelihood of consent were smaller practice size (practices with greater than eight GPs as compared with those with one to two GPs, odds ratio 0.40, 95% confidence interval 0.21-0.75) and older GPs. CONCLUSIONS: The strong association of consent with year of recruitment may be due to changes in trial procedures and investigator training. If so, this has important implications for the conduct of future trials.     

A brief measure of perceived understanding of informed consent in a clinical trial was validated

BACKGROUND AND OBJECTIVE: To develop and evaluate an Informed Consent Questionnaire (ICQ) for measuring self-reported perceived understanding of informed consent in a randomized clinical trial. METHODS: The study was embedded in a Department of Veterans Affairs randomized clinical trial of Gulf War veterans' illnesses (CSP#470). The trial was initiated in May 1999 at 20 hospitals and concluded in September 2001; 1,092 participants were enrolled and followed for 12 months. The reliability and validity sample included 1,086 participants evaluated at baseline, 906 at 3 months, 929 at 6 months, and 910 at 12 months. The psychometric evaluations included tests of acceptability (based on missing data, endorsement frequencies, and floor/ceiling effects), item reduction, internal consistency, and construct validity (based on Cronbach's alpha coefficients, item-total correlations, and principal components analysis). RESULTS: The ICQ had >5% missing information on some questions at baseline, indicating poor acceptability prior to the initiation of the trial; however, the scale had good acceptability at each of the follow-up visits. Psychometric evaluation following standard item reduction techniques confirmed the reliability and validity of a four-item subscale of the ICQ (ICQ-4). CONCLUSIONS: The ICQ-4 is a simple and psychometrically sound self-report measure of perceived understanding of informed consent.     

A randomized controlled trial of hypnotherapy for smoking cessation

A randomized controlled study in a family practice setting was conducted on the use of hypnosis in helping people quit smoking. In the hypnosis group 21 percent of patients quit smoking by the three month follow-up compared with 6 percent in the control group. By six months there were no significant differences between the two groups, and at one year 22 percent in the hypnosis group and 20 percent in the control group had quit. The only significant predictor of success with quitting was having a college education.     

Patient satisfaction with teledermatology: quantitative and qualitative results from a randomized controlled trial

As part of a randomized controlled trial involving 208 dermatology patients, a quantitative and qualitative study was undertaken to explore patients' satisfaction with a specialist dermatological opinion and further management obtained through either a traditional outpatient consultation (control group) or an asynchronous teleconsultation (telemedicine group). There was a response rate of 71% to the quantitative patient satisfaction survey (148 replies from 208 distributed questionnaires). The responders comprised 80 of the 111 telemedicine patients (72%) and 68 of the 97 control patients (70%). Overall levels of patient satisfaction were high in both groups, and there was no significant difference between them. Ninety per cent of patients in the control group were satisfied with their overall care, compared with 81% in the telemedicine group, and 87% of patients in the control group were satisfied with their overall management, compared with 84% in the telemedicine group. Follow-up qualitative interviews with 30 of the participants also suggested that patients were generally positive about their care and management, regardless of group, age or gender. Receiving a diagnosis, treatment and cure, receiving adequate information and explanations, the need to be taken seriously, the need for individualized personal care, and the importance of a short waiting time for an appointment and treatment were all aspects of care and management most likely to result in patient satisfaction, regardless of modality.     

Proposing modesty for informed consent

The extension of informed consent into social science research has met with considerable opposition. The history and concept of informed consent, however, is based on a substantive ethical notion of the research relationship as informed and voluntary that is appropriate for social science research relationships. Yet social science research might sometimes be different from health research in ways that justify a different approach to informed consent and research relationships. Social science research tends to have a lower magnitude of risk, usually does not need to disrupt the therapeutic assumption common in health research contexts or when researchers are health professionals, and recruitment is sometimes incremental and reflects a building of trust and development of the research participant's role. These differences may sometimes justify novel approaches to the research relationship and require case-by-case evaluation to determine their relevance to establishing the informed and voluntary nature of the relationship through the use of informed consent procedures. Ultimately, respect for research participants requires social research into practices that can support or replace informed consent. The institutional role of informed consent and the goal of informed and voluntary research participation serve modest but important roles in health and social research. Their proper role in health and social research requires flexibility and experimentation, but does not justify abdication of informed consent or the notion of informed and voluntary participation.     

Alternatives to the randomized controlled trial

Public health researchers are addressing new research questions (e.g., effects of environmental tobacco smoke, Hurricane Katrina) for which the randomized controlled trial (RCT) may not be a feasible option. Drawing on the potential outcomes framework (Rubin Causal Model) and Campbellian perspectives, we consider alternative research designs that permit relatively strong causal inferences. In randomized encouragement designs, participants are randomly invited to participate in one of the treatment conditions, but are allowed to decide whether to receive treatment. In quantitative assignment designs, treatment is assigned on the basis of a quantitative measure (e.g., need, merit, risk). In observational studies, treatment assignment is unknown and presumed to be nonrandom. Major threats to the validity of each design and statistical strategies for mitigating those threats are presented.