Search PubMed⌕ Search

Biomedical subjects

Marion K Campbell

Publications and source records attributed to Marion K Campbell.

At least 19 recordsLinked to original sources
PubMed2006

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

BACKGROUND: Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). METHODS: In-depth semi-structured telephone interviews were conducted in 2003-04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. RESULTS: The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. CONCLUSION: This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research.

Journal Article↗
PubMed2006

Protocol for stage 1 of the GaP study (Genetic testing acceptability for Paget's disease of bone): an interview study about genetic testing and preventive treatment: would relatives of people with Paget's disease want testing and treatment if they were available?

BACKGROUND: Paget's disease of bone (PDB) is characterised by focal increases in bone turnover, affecting one or more bones throughout the skeleton. This disrupts normal bone architecture and causes pain, deformity, deafness, osteoarthritis, and fractures. Genetic factors are recognised to play a role in PDB and it is now possible to carry out genetic tests for research. In view of this, it is timely to investigate the clinical potential for a programme of genetic testing and preventative treatment for people who have a family history of PDB, to prevent or delay the development of PDB. Evidence from non-genetic conditions, that have effective treatments, demonstrates that patients' beliefs may affect the acceptability and uptake of treatment. Two groups of beliefs (illness and treatment representations) are likely to be influential. Illness representations describe how people see their illness, as outlined in Leventhal's Self-Regulation Model. Treatment representations describe how people perceive potential treatment for their disease. People offered a programme of genetic testing and treatment will develop their own treatment representations based on what is offered, but the beliefs rather than the objective programme of treatment are likely to determine their willingness to participate. The Theory of Planned Behaviour is a theoretical model that predicts behaviours from people's beliefs about the consequences, social pressures and perceived control over the behaviour, including uptake of treatment. METHODS/DESIGN: This study aims to examine the acceptability of genetic testing, followed by preventative treatment, to relatives of people with PDB. We aim to interview people with Paget's disease, and their families, from the UK. Our research questions are:1. What do individuals with Paget's disease think would influence the involvement of their relatives in a programme of genetic testing and preventative treatment? What do relatives of Paget's disease sufferers think would influence them in accepting an offer of a programme of genetic testing and preventative treatment? DISCUSSION: Our research will be informed by relevant psychological theory: primarily the Self-Regulation Model and the Theory of Planned Behaviour. The results of these interviews will inform the development of a separate questionnaire-based study to explore these research questions in greater detail.

Adult↗
PubMed2006

What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies.

BACKGROUND: A commonly reported problem with the conduct of multicentre randomised controlled trials (RCTs) is that recruitment is often slower or more difficult than expected, with many trials failing to reach their planned sample size within the timescale and funding originally envisaged. The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies: the UK Medical Research Council (MRC) and the Health Technology Assessment (HTA) Programme. METHODS: The cohort of trials was identified from the administrative databases held by the two funding bodies. 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria. The full scientific applications and subsequent trial reports submitted by the trial teams to the funders provided the principal data sources. Associations between trial characteristics and recruitment success were tested using the Chi-squared test, or Fisher's exact test where appropriate. RESULTS: Less than a third (31%) of the trials achieved their original recruitment target and half (53%) were awarded an extension. The proportion achieving targets did not appear to improve over time. The overall start to recruitment was delayed in 47 (41%) trials and early recruitment problems were identified in 77 (63%) trials. The inter-relationship between trial features and recruitment success was complex. A variety of strategies were employed to try to increase recruitment, but their success could not be assessed. CONCLUSION: Recruitment problems are complex and challenging. Many of the trials in the cohort experienced recruitment difficulties. Trials often required extended recruitment periods (sometimes supported by additional funds). While this is of continuing concern, success in addressing the trial question may be more important than recruitment alone.

Journal Article↗
PubMed2005

[The CONSORT statement for cluster randomised trials].

With the publication of the CONSORT statement there is now increased awareness of the need to adequately report the findings of randomised controlled trials. The CONSORT statement includes a checklist of items that should be addressed in the trial report. The original CONSORT statement was developed to ensure the appropriate reporting of parallel group randomised controlled trials in which individual participants are allocated to different intervention groups. In cluster randomised trials, however, groups of participants, rather than individuals, are randomly allocated to study groups. The process of allocating groups of participants raises additional reporting considerations and led to the publication of an extension to the CONSORT statement specifically for cluster randomised trials. In this paper we review the CONSORT extension to cluster randomised trials, outlining the special features of the cluster randomised trial which must be considered.

Authorship↗
PubMed2005

Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, randomised, double blind, placebo controlled trial.

OBJECTIVE: To examine whether supplementation with multivitamins and multiminerals influences self reported days of infection, use of health services, and quality of life in people aged 65 or over. DESIGN: Randomised, placebo controlled trial, with blinding of participants, outcome assessors, and investigators. SETTING: Communities associated with six general practices in Grampian, Scotland. PARTICIPANTS: 910 men and women aged 65 or over who did not take vitamins or minerals. INTERVENTIONS: Daily multivitamin and multimineral supplementation or placebo for one year. MAIN OUTCOME MEASURES: Primary outcomes were contacts with primary care for infections, self reported days of infection, and quality of life. Secondary outcomes included antibiotic prescriptions, hospital admissions, adverse events, and compliance. RESULTS: Supplementation did not significantly affect contacts with primary care and days of infection per person (incidence rate ratio 0.96, 95% confidence interval 0.78 to 1.19 and 1.07, 0.90 to 1.27). Quality of life was not affected by supplementation. No statistically significant findings were found for secondary outcomes or subgroups. CONCLUSION: Routine multivitamin and multimineral supplementation of older people living at home does not affect self reported infection related morbidity. TRIAL REGISTRATION: ISRCTN: 66376460.

Aged↗
PubMed2005

A centralised public information resource for randomised trials: a scoping study to explore desirability and feasibility.

BACKGROUND: There are currently several concerns about the ways in which people are recruited to participate in randomised controlled trials, the low acceptance rates among people invited to participate, and the experiences of trial participants. An information resource about on-going clinical trials designed for potential and current participants could help overcome some of these problems. METHODS: We carried out a scoping exercise to explore the desirability and feasibility of establishing such a resource. We sought the views of a range of people including people who were considering taking part in a trial, current trial participants, people who had been asked but refused to participate in a trial, consumer group representatives and researchers who design and conduct trials. RESULTS: There was broad-based support for the concept of a centralised information resource for members of the public about on-going and recently completed clinical trials. Such an information resource could be based on a database containing standardised information for each trial relating to the purpose of the trial; the interventions being compared; the implications of participation for participants; and features indicative of scientific quality and ethical probity. The usefulness of the database could be enhanced if its search facility could allow people to enter criteria such as a disease and geographic area and be presented with all the trials relevant to them, and if optional display formats could allow them to view information in varying levels of detail. Access via the Internet was considered desirable, with complementary supported access via health information services. The development of such a resource is technically feasible, but the collation of the required information would take a significant investment of resources. CONCLUSION: A centralised participant oriented information resource about clinical trials could serve several purposes. A more detailed investigation of its feasibility and exploration of its potential impacts are required.

Databases as Topic↗
PubMed2005

Low dietary potassium intakes and high dietary estimates of net endogenous acid production are associated with low bone mineral density in premenopausal women and increased markers of bone resorption in postmenopausal women.

BACKGROUND: The Western diet may be a risk factor for osteoporosis. Excess acid generated from high protein intakes increases calcium excretion and bone resorption. Fruit and vegetable intake could balance this excess acidity by providing alkaline salts of potassium. Algorithms based on dietary intakes of key nutrients can be used to approximate net endogenous acid production (NEAP) and to explore the association between dietary acidity and bone health. OBJECTIVE: We investigated the relation between dietary potassium and protein, NEAP (with an algorithm including the ratio of protein to potassium intake), and potential renal acid load (with an algorithm including dietary protein, phosphorous, potassium, magnesium, and calcium) and markers of bone health. DESIGN: Measurements of bone mineral density (BMD) (n = 3226) and urinary bone resorption markers (n = 2929) at the lumbar spine and femoral neck were performed in perimenopausal and early postmenopausal women aged 54.9 +/- 2.2 y (x +/- SD) in 1997-1999. BMD (g/cm(2)), free pyridinoline (fPYD), and free deoxypyridinoline (fDPD) were expressed relative to creatinine. Dietary intake was assessed with a food-frequency questionnaire. RESULTS: Comparison of the highest with the lowest quartile of potassium intake or the lowest with the highest NEAP showed a 6-8% increase in fPYD/creatinine and fDPD/creatinine. A difference of 8% in BMD was observed between the highest and lowest quartiles of potassium intake in the premenopausal group (n = 337). CONCLUSIONS: Dietary potassium, an indicator of NEAP and fruit and vegetable intake, may exert a modest influence on markers of bone health, which over a lifetime may contribute to a decreased risk of osteoporosis.

Acid-Base Equilibrium↗
PubMed2005

An integrated approach to consumer representation and involvement in a multicentre randomized controlled trial.

Although, consumer involvement in individual studies is often limited, their involvement in guiding health research is generally considered to be beneficial. This paper outlines our experiences of an integrated relationship between the organisers of a clinical trial and a consumer organisation. The PRISM trial is a UK multicentre, randomized controlled trial comparing treatment strategies for Paget's disease of the bone. The National Association for the Relief of Paget's Disease (NARPD) is the only UK support group for sufferers of Paget's disease and has worked closely with the PRISM team from the outset. NARPD involvement is integral to the conduct of the trial and specific roles have included: peer-review; trial steering committee membership; provision of advice to participants, and promotion of the trial amongst Paget's disease patients. The integrated relationship has yielded benefits to both the trial and the consumer organisation. The benefits for the trial have included: recruitment of participants via NARPD contacts; well-informed participants; unsolicited patient advocacy of the trial; and interested and pro-active collaborators. For the NARPD and Paget's disease sufferers, benefits have included: increased awareness of Paget's disease; increased access to relevant health research; increased awareness of the NARPD services; and wider transfer of diagnosis and management knowledge to/from health care professionals. Our experience has shown that an integrated approach between a trial team and a consumer organisation is worthwhile. Adoption of such an approach in other trials may yield significant improvements in recruitment and quality of participant information flow. There are, however, resource implications for both parties.

Consumer Organizations↗
PubMed2005

Determinants of the intracluster correlation coefficient in cluster randomized trials: the case of implementation research.

The objective of this research was to identify determinants of the magnitude of intracluster correlation coefficients (ICCs) in cluster randomized trials from the field of implementation research. A survey of experts was conducted to generate a priori hypotheses of factors that might affect ICC size. Hypotheses were tested on empirical estimates of ICCs calculated from 21 implementation research datasets, mainly from the UK. Effects of setting (primary or secondary care), type of variable (process or outcome), type of measurement (objective or subjective), prevalence of outcome and size of cluster were tested. In total, 220 ICCs were available (range 0 to 0.415). Significant differences in ICC magnitude were found. The ICCs were significantly higher for process than for outcome variables, and for secondary care outcomes compared with primary care outcomes. The effects of prevalence and size were less clear cut. There was no evidence to suggest that type of measurement affected ICC size. In conclusion, accurate estimates of ICCs are essential for sample size calculations for cluster randomized trials of professional behaviour change interventions. This study demonstrates that ICCs are sensitive to a number of trial factors, particularly setting and outcome type. These factors must be considered when planning such cluster randomized trials.

Biomedical Research↗
PubMed2004

Influence of weight and weight change on bone loss in perimenopausal and early postmenopausal Scottish women.

Weight is recognized as an important factor in determining an individual's risk of osteoporosis. However, little is known about whether weight or weight change influences bone loss around the time of the menopause, and the relationship with energy intake and physical activity level remains largely undefined. Healthy premenopausal women (1,064 selected from a random population of 5,119 women aged 45-54 years at baseline) each had bone mineral density (BMD), weight and height measurements, and completed a food frequency and physical activity questionnaire. Of the original participants, 907 women (85.2%) returned 6.3 +/- 0.6 years later for repeat BMD measurements, and 896 women completed the questionnaires. Bone loss at the hip (FN) and spine (LS) occurred before the menopause. Weight change rather than weight was associated with FN BMD loss (r=0.102, p=0.002), but weight at follow-up was associated with LS BMD change (r=0.105, p=0.002). Although an increase in physical activity level (PAL) appeared to be beneficial for FN BMD in women who were heavy weight gainers, PAL was associated with increased LS BMD loss in women who lost weight. For current HRT users, neither weight nor weight change was associated with change in BMD. Postmenopausal women not taking HRT should be made aware that low body weight or losing weight during this particularly vulnerable period may worsen bone loss.

Analysis of Variance↗
PubMed2004

Intracluster correlation coefficients in cluster randomized trials: empirical insights into how should they be reported.

BACKGROUND: Increasingly, researchers are recognizing that there are many situations where the use of a cluster randomized trial may be more appropriate than an individually randomized trial. Similarly, the need for appropriate standards of reporting of cluster trials is more widely acknowledged. METHODS: In this paper, we describe the results of a survey to inform the appropriate reporting of the intracluster correlation coefficient (ICC)--the statistical measure of the clustering effect associated with a cluster randomized trial. RESULTS: We identified three dimensions that should be considered when reporting an ICC--a description of the dataset (including characteristics of the outcome and the intervention), information on how the ICC was calculated, and information on the precision of the ICC. CONCLUSIONS: This paper demonstrates the development of a framework for the reporting of ICCs. If adopted into routine practice, it has the potential to facilitate the interpretation of the cluster trial being reported and should help the development of new trials in the area.

Cluster Analysis↗
PubMed2004

Low back pain: influence of early MR imaging or CT on treatment and outcome--multicenter randomized trial.

PURPOSE: To establish whether early use of magnetic resonance (MR) imaging or computed tomography (CT) influences treatment and outcome of patients with low back pain (LBP) and whether it is cost-effective. MATERIALS AND METHODS: In a multicenter randomized study, two imaging policies for LBP were compared in 782 participants with symptomatic lumbar spine disorders who were referred to orthopedists or neurosurgeons. Participants were randomly allocated to early (393 participants; mean age, 43.9 years; range, 16-82 years) or delayed selective (389 participants; mean age, 42.8 years; range, 14-82 years) imaging groups. Delayed selective imaging referred to imaging restricted to patients in whom a clear clinical need subsequently developed. Main outcome measures were Aberdeen Low Back Pain (ALBP) score, Short Form 36 (SF-36) score (for multidimensional health status), EuroQol (EQ-5D) score (for quality-adjusted life-year [QALY] estimates), and healthcare resource use at 8 and 24 months after randomization. Data were evaluated with analysis of covariance, ordinal logistic regression analysis, and chi(2) and Mann-Whitney tests. RESULTS: Both groups showed improvement in ALBP score, but this was greater in the early group (adjusted mean difference between groups, -3.05 points [95% CI: -5.16, -0.95; P =.005] and -3.62 points [95% CI: -5.92, -1.32; P =.002] at 8 and 24 months, respectively). Scores for SF-36 (bodily pain domain) and EQ-5D were also significantly better at 24 months. Clinical treatment was similar in both groups. Differences in total costs reflected cost of imaging. Imaging provided an adjusted mean additional QALY of 0.041 during 24 months at a mean incremental cost per QALY of $2,124. CONCLUSION: Early use of imaging does not appear to affect treatment overall. Decisions about the use of imaging depend on judgments concerning whether the small observed improvement in outcome justifies additional cost.

Adolescent↗
PubMed2004

Sample size calculator for cluster randomized trials.

Cluster randomized trials, where individuals are randomized in groups are increasingly being used in healthcare evaluation. The adoption of a clustered design has implications for design, conduct and analysis of studies. In particular, standard sample sizes have to be inflated for cluster designs, as outcomes for individuals within clusters may be correlated; inflation can be achieved either by increasing the cluster size or by increasing the number of clusters in the study. A sample size calculator is presented for calculating appropriate sample sizes for cluster trials, whilst allowing the implications of both methods of inflation to be considered.

Algorithms↗
PubMed2004

Lower estimates of net endogenous non-carbonic acid production are positively associated with indexes of bone health in premenopausal and perimenopausal women.

BACKGROUND: The link between acid-base homeostasis and skeletal integrity has gained increasing prominence in the literature. Estimation of the net rate of endogenous non-carbonic acid production (NEAP) from dietary protein and potassium content enables exploration of the effects of dietary acidity or alkalinity on bone. OBJECTIVE: The study aimed to ascertain whether lower dietary acidity (lower dietary protein intake but higher potassium intake-ie, low estimate of NEAP) was associated with greater axial and peripheral bone mass and less bone turnover, independent of key confounding factors. DESIGN: Baseline (cross-sectional) results of a population-based study were examined further. The database includes spine and hip bone mineral density (BMD) in 1056 premenopausal or perimenopausal women aged 45-54 y and forearm bone mass and the urinary markers of bone resorption in 62 women. A validated food-frequency questionnaire was used to measure dietary intakes. RESULTS: Lower estimates of energy-adjusted NEAP were correlated with greater spine and hip BMD and greater forearm bone mass (P < 0.02 to P < 0.05). Hip and forearm bone mass decreased significantly across increasing quartiles of energy-adjusted NEAP (P < 0.02 to P < 0.03), and trends at the spine were similar (P < 0.09). Differences remained significant after adjustment for age, weight, height, and menstrual status. Lower estimates of energy-adjusted NEAP were also correlated with lower excretion of deoxypyridinoline and were significant predictors of spine and forearm bone mass. CONCLUSIONS: These novel findings provide evidence of a positive link between a ratio of lower protein to higher potassium dietary intake (ie, less dietary acid) and skeletal integrity.

Bone Density↗
PubMed2004

Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids.

BACKGROUND: The menopausal transition is characterized by rapid bone loss. Few data exist on the role of nutrition. OBJECTIVE: The objective of the study was to ascertain which dietary factors influence perimenopausal skeletal loss. DESIGN: A longitudinal study was conducted of 891 women aged 45-55 y at baseline and 50-59 y at follow-up 5-7 y later. Bone mineral density (BMD) was measured by using dual-energy X-ray absorptiometry at the lumbar spine and femoral neck (FN). Nutrient intakes were assessed after the baseline visit and 5 y later, by using the same food-frequency questionnaire. RESULTS: After adjustment for energy intake and other confounders, higher intakes of calcium were correlated with change in FN BMD (ie, reduced loss) (r = 0.073, P < 0.05), and the intake of modest amounts of alcohol was associated with less lumbar spine bone loss (P < 0.01 for quartile of alcohol intake). Greater FN BMD loss was associated with increased intake of polyunsaturated fatty acids (r = -0.110, P < 0.01), monounsaturated fatty acids (r = -0.069, P < 0.05), retinol (r = -0.067; P < 0.05), and vitamin E (r = -0.110; P < 0.01). The latter 2 nutrients were highly correlated with polyunsaturated fatty acids. For premenopausal women, calcium and nutrients found in fruit and vegetables (vitamin C, magnesium, and potassium) were associated with FN BMD, and calcium, vitamin C, and magnesium were associated with change in FN BMD. CONCLUSIONS: Although menopausal status and hormone replacement therapy use dominate women's bone health, diet may influence early postmenopausal bone loss. Fruit and vegetable intake may protect against premenopausal bone loss.

Bone Density↗
PubMed2004

The effects of an open design on trial participant recruitment, compliance and retention--a randomized controlled trial comparison with a blinded, placebo-controlled design.

BACKGROUND: In randomized trials there may be no overriding reason whether or not to have a placebo control. PURPOSE: We assessed the effects of an open trial design (no placebo and people know what tablets they are given) compared with a blinded, placebo-controlled design on recruitment, compliance and retention within a randomized trial of secondary osteoporotic fracture prevention. METHODS: We undertook a randomized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture, recruited in a UK teaching hospital. Randomization was 2:1 in favour of the blinded, placebo-controlled trial design. RESULTS: From 180 eligible participants randomized to receive information based on the open trial design, 134 (74.4%) consented to take part, compared with 233 (65.1%) of 358 people randomized to the blinded, placebo-controlled design (difference 9.4%, 95% confidence interval 1.3-17.4%). Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded, placebo-controlled design. There was no significant difference in tablet compliance. Open trial participants were more likely to remain in the trial for one year (difference 13.9%, 95% confidence interval 3.1-24.6%), mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group (difference 23.6%, 95% confidence interval 11.9-35.2%). The odds ratio for reporting an adverse event in the open trial compared to the blinded, placebo-controlled design was 0.64 (95% confidence interval 0.28-1.49), and for reporting a fracture was 0.81 (0.36-1.85). CONCLUSIONS: We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power, but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial.

Aged↗