Nat Wright

Non-commercial clinical trials of a medicinal product: can they survive the current process of research approvals in the UK?

Over recent years, considerable attention has been paid to the National Health Service (NHS) research governance and ethics approvals process in the UK. New regulations mean that approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) is now also needed for conducting all clinical trials. Practical experience of gaining MHRA and sponsorship approval has yet to be described and critically explored in the literature. Our experience, from start to finish, of applying for these four approvals for a multicentre randomised controlled trial of two licensed drugs for opiate detoxification in the prison setting is described here. In addition, the implications of the approvals process for research projects, particularly clinical trials, in terms of time and funding, and also indirect implications for NHS patients are discussed. Inconsistencies are discussed and suggestions that could improve and streamline the overall process are made. The current approvals process could now be hindering non-commercial clinical trials, leading to a loss of important evidence-based medical information.

Exchange, deceit, risk and harm: The consequences for women of receiving injections from other drug users

Aims: To explore the consequences for women of being injected with illicit drugs. Methods: In-depth interviews with 45 women injecting drug users who have been injected by other people. Findings: Womens reliance on others to administer injections meant they had less control over their drug use. Exchanging drugs as currency for being injected was common and women had little choice but to provide the injector with drugs. Being injected by others often caused the recipient physical harm. Previous experience of deception and harm meant women became more knowledgeable about their injectors intentions and subsequently tried to reduce future damage when being injected. Women appeared to be confused about the risks associated with being injected and the perceived risks were often complex and polarized. Understanding the context and nature of being injected is important for services when working with injection recipients. Conclusions: This work uncovered ideas about a complex area and highlights the importance for those working with drug users to pay attention to this. Increased training and awareness for drug-service staff about factors influencing being injected and the potential associated risks is recommended. Reinforcing current harm-reduction messages and providing related advice to injection recipients is also important. In improving the knowledge and awareness about being injected, women recipients may gain increased choice and agency in the injection process.

Exploring prison buprenorphine misuse in the United Kingdom: A qualitative study of former prisoners

The United Kingdom Ministry of Justice recently highlighted the extent of buprenorphine (Subutex) misuse in English andWelsh prisons, naming it the third most misused drug overall. Yet little is known regarding how illicit buprenorphine is obtained in prison and what influences prisoners to use it. Qualitative research was used to explore prison drug using practices. Thirty men who were former prisoners with a history of injecting drug use were interviewed in depth about their illicit prison drug use, including buprenorphine. Interviews were conducted over 18 months, from August 2006 to January 2008 and were analysed using Framework. The misuse of Subutex by snorting emerged as a significant theme. Accounts suggested that the diversion of prison prescribed Subutex was widespread and prisoners used various tactics to obtain the medication. Various complex and interlinked reasons were given to explain why Subutex was snorted in prison. The main motivation for snorting was to experience a prolonged euphoric opiate effect, believed to help to combat the boredom of being in prison. The price of illicit Subutex in prison was linked to its availability, but it was generally cheaper than heroin, thus contributing to its use. Participantsnarratives identified the belief that snorting Subutex in prison was not risk free, but risks were lower than continuing to use other drugs, particularly injecting illicit opiates. The implications of prison Subutex misuse for prisoners, prison medical services, commissioners, and prescribing policy and practice are discussed.

Is peer injecting a form of intimate partner abuse? A qualitative study of the experiences of women drug users

Women are over-represented as the recipients of injections of illicit drugs and are often injected by their intimate partners. This study used qualitative research to explore women drug users’ experiences of abuse from intimate partners when being injected with illicit drugs. In-depth interviews were conducted with 45 women drug users in the city of Leeds and the area of North Nottinghamshire, UK. The practice of peer injecting illicit drugs places women recipients at risk of physical, economic and emotional abuse from their male intimate partner injectors. However, this was not a universal feature. In trusting, supportive intimate partner relationships peer injecting took place through reciprocal arrangements. Moving away from peer injecting was technically and emotionally difficult for women and rarely straightforward. The implications of the work are discussed as clinicians and wider drug service staff should be aware of the possibility of abuse and enquire about peer injecting when consulting with women injecting drug users. However, clinicians should avoid working within a simplistic clinical framework that views all peer injecting as intrinsically abusive. More research is needed to provide evidence for best practice. Until then, generic principles of best practice management of intimate partner abuse could apply, including enhancing womens motivation to effect change in an abusive situation.

Needle fear among women injecting drug users: a qualitative study

Objective: To describe elements of needle phobia amongst women injecting dug users and discuss the associated health implications. Design: Qualitative research using in depth interviews. Participants: Forty‐five injecting drug‐using (IDU) women who had experience of being injected with illicit drugs by other drug users. Results/Findings: Women injecting drug users displayed elements of needle phobia as they had a strong fear of needles. Most were fearful of needles prior to their first experience of injecting drug use. For some, their fear of needles continued during their later injecting experiences. Being afraid of needles, however, was not limited to injecting drug use as many women feared medical procedures that involved needles. They responded to this by refusing or delaying medical procedures involving needles, including blood tests and immunizations. Conclusions: Some women IDUs have a strong fear of needles and are concerned about medical procedures involving needles. Clinicians, especially those working with drug users, need to be aware that fear of needles can be a problem for some injecting drug users and this has health and clinical practice implications. Needle fear may potentially affect an injecting drug users engagement with and receipt of health care. Alternative methods of administration should therefore be investigated if this reduces anxiety and ensures that injecting drug using patients receive necessary health care.

Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs

Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive for global elimination of HCV infection.

Buprenorphine dosing choices in specific populations: review of expert opinion.

ABSTRACT Introduction: Treatment of opioid dependence with buprenorphine improves outcomes. Typical dosing ranges for all patients from clinical evidence and as defined in the product information are wide. For specific groups with complex clinical scenarios, there is no clear consensus on dosing choices to achieve best possible outcomes. Areas covered: The doses of buprenorphine used in 6 European countries was reviewed. A review of published evidence supported rapid induction with buprenorphine and the benefits of higher doses but did not identify clearly useful guidance on dosing choices for groups with complex clinical scenarios. An expert group of physicians with experience in addiction care participated in a discussion meeting to share clinical practice experience and develop a consensus on dosing choices. Expert opinion: There was general agreement that treatment outcomes can be improved by optimising buprenorphine doses in specific subgroups. Specific groups in whom buprenorphine doses may be too low and who could have better outcomes with optimised dosing were identified on the basis of clinical practice experience. These groups include people with severe addiction, high tolerance to opioids, and psychiatric comorbidities. In these groups it is recommended to review dosing choices to ensure buprenorphine dosing is sufficient.

The Impact of Misuse and Diversion of Opioid Substitution Treatment Medicines: Evidence Review and Expert Consensus.

Background/Aims: Opioid substitution treatment (OST) improves outcomes in opioid dependence. However, controlled drugs used in treatment may be misused or diverted, resulting in negative treatment outcomes. This review defines a framework to assess the impact of misuse and diversion. Methods: A systematic review of published studies of misuse and diversion of OST medicines was completed; this evidence was paired with expert real-world experience to better understand the impact of misuse and diversion on the individual and on society. Results: Direct impact to the individual includes failure to progress in recovery and negative effects on health (overdose, health risks associated with injecting behaviour). Diversion of OST has impacts on a community that is beyond the intended OST recipient. The direct impact includes risk to others (unsupervised use; unintended exposure of children to diverted medication) and drug-related criminal behavior. The indirect impact includes the economic costs of untreated opioid dependence, crime and loss of productivity. Conclusion: While treatment for opioid dependence is essential and must be supported, it is vital to reduce misuse and diversion while ensuring the best possible care. Understanding the impact of OST misuse and diversion is key to defining strategies to address these issues.

Preventing radicalisation and terrorism: is there a GP response?

Radicalisation is a process by which an individual or group comes to adopt increasingly extreme political, social, or religious ideals and aspirations that reject or undermine the status quo.1 Terrorism is seen as a consequence of such extreme ideals and is defined as, ‘any action … that is intended to cause death or serious bodily harm to civilians or non-combatants, when the purpose of such an act, by its nature and context, is to intimidate a population, or to compel a government or an international organisation to do or to abstain from doing any act.’ 2 Internationally, in the last year there has been an escalation in terrorist acts.3nnCommentators have explored whether there is a psychological profile of a terrorist, with early commentators proposing mental illness, sociopathy, and psychopathy as risk factors for terrorist activity.4 However, emotionally unstable individuals tend not to be recruited by terrorist organisations as they are usually deemed too much of a security risk.5 However, there is a link between ill-health and terrorism; individuals living in war zones commonly experience post-traumatic stress disorder, ‘survivor’s guilt’, and bereavement of close friends or families. For some, such traumatic life-events are factors leading to committing terrorist acts.6 Symptoms of guilt, anxiety, grief, and a need for vengeance, combined with a strong religious belief of a better afterlife in which they will rejoin lost loved ones, explains some terrorist acts.7nnHowever, while individual illness may be a contributory factor in an individual becoming radicalised, terrorist activity cannot be explained by a simplistic model of individual illness. Rather …

Assessing the predictability of self-harm in a high-risk adult prisoner population: a prospective cohort study

BackgroundPrisoners are at increased risk of self-harm and when either intent is expressed, or an act of self-harm carried out, prisoners in the UK are subject to self-harm/suicide monitoring (referred to as “open ACCT” monitoring). However, there is a paucity of validated instruments to identify risk of self-harm in prisoner populations. In response to the need to support prison staff to determine who is at increased risk of self-harm or repeat self-harm, the aim of this study was to determine whether any pre-existing, standardised instruments could usefully identify future self-harm events in prisoners undergoing ACCT monitoring.MethodsA multi-stage prospective cohort study was conducted, where the Prison Screening Questionnaire (PriSnQuest), a modified Borderline Symptom List-23 (BSL-23), Self-Harm Inventory (SHI), Patient Health Questionnaire-9 (PHQ-9) and Clinical Outcomes in Routine Evaluation – Outcome Measure (CORE-OM) instruments were administered to prisoners aged 18 and above, who were judged to be at an increased risk of self-harm (on open ACCT monitoring) during the recruitment phase. A 6-month follow-up determined self-harm occurrence since baseline, and Area-Under-the-Curve (AUC) analysis examined the ability of the instruments to predict future self-harm.ResultsPrison records established that 29.1% self-harmed during the follow up period, involving a total of 423 self-harm events reported from 126 individuals, followed up for 66,789 prisoner days (median 167xa0days; IQR 71–207.5xa0days). This translated to an ‘event incidence’ of 6.33 per 1000 prisoner days of those who had been placed upon an ACCT, or ‘prisoner incidence’ of 1.89 per 1000xa0days, with considerable variation for both gender and participating prisons. None of the summary scores derived from the selected instruments showed a meaningful ability to predict self-harm, however, exploratory logistic regression analysis of individual background and instrument items revealed gender-specific item sets which were statistically significant in predicting future self-harm.ConclusionsProspective self-harm was not predicted by any of the pre-existing instruments that were under consideration. Exploratory logistic regression analysis did reveal gender-specific item sets, producing predictive algorithms which were statistically significant in predicting future self-harm; however, the operational functionality of these item sets may be limited.