Monday Media: Episode 1, 15th October 2018

I’ve talked before on this blog about how I do some freelance writing projects along side my full time job, and today I want to start a new series of blog posts that originate from a conversation I had with a client a while ago. One of the regular projects that I work on is a weekly recap of news; every single week (through thesis write up and everything!), I write a news recap piece for Synthego. Synthego are based in Silicon Valley, and they have a product portfolio spanning software and synthetic RNA kits that are designed to support scientists and researchers with CRISPR gene editing processes. I’ve worked with Synthego for over 2 years now, and this little recap of news has become a normal part of my week. I find these types of posts really interesting to write even though I don’t work in a lab or have anything to do with CRISPR or gene editing day-to-day, so I figured it might be good to make a little news recap of my own each week.

I’m not sure if this will be a weekly thing just yet (let’s see if anyone actually reads it first…), but I’m going to use these posts to highlight new research, interesting articles and other forms of media (blog posts, podcasts, YouTube videos etc) that are related to things I find interesting – primarily trials and trial methods, but likely a bit of public engagement/involvement and research integrity thrown in there too.

So, here goes! Let me know what you think and whether you’d like to see these types of posts become a regular thing on the blog.

Research Paper: The effect of optimised patient information materials on recruitment in a lung cancer screening trial: an embedded recruitment trial

Full disclaimer on this one – I know some of the team behind this paper; one of them was (I just had to go back and delete the word ‘is’, it’s still very strange to not be a PhD student anymore) my PhD supervisor, and I’ve been lucky enough to work with a few of them on other projects too. Even so, it’s still interesting and it’s still useful.

This study focusses on the content of participant information leaflets; these are the leaflets that people are given when they are approached to take part in a trial, it should contain all the information they need to make a decision about trial participation, and it should be presented in a format that is accessible and easy to digest. In reality, a lot of participant information leaflets are super long, very text-heavy, and often make people (myself included) groan just thinking about reading them. The team behind this study designed and conducted an embedded study (also called SWATs or studies within trials – I mentioned them in a previous blog post here), looking at participant information leaflets used within a host trial that aimed to assess the effectiveness of a new test in reducing the incidence of patients with late-stage lung cancer at diagnosis compared with standard care. Potential participants approached for participation in the host trial were randomised to receive the original participant information leaflet and accompanying letter (control group) or optimised versions of these materials which had undergone user testing and a process of re-writing, re-organisation and professional graphic design (intervention group). The primary outcome was the number of patients recruited to the host trial, and the secondary outcome was the proportion of patients expressing an interest in participating in the host trial (just a note – I’ll be doing a post all about outcomes soon as that’s what my next research project will focus on, keep an eye out for it over the coming months!).

The results of this embedded study suggest that optimised patient information materials made little difference to the proportion of patients positively responding to a trial invitation or to the proportion subsequently randomised to the host trial. I’m interested as to why this is – personally I think it’s something to do with the verbal information that potential participants get alongside these leaflets, but I guess that’s a question for a future study! Read the full paper here.

Research paper: Global public attitudes about clinical research and patient experiences with clinical trials

A new study published in JAMA from researchers at The Center for Information and Study on Clinical Research Participation in Boston, Massachusetts, caught my eye this week. The team surveyed 12,427 people in 2017 about their attitudes and understanding of clinical research, these individuals represented 68 countries and included 2,194 clinical trial participants.

The survey found that 84.5% of respondents perceived clinical research to be very important to the discovery and development of new medicines, but 59% were unable to name a place where studies were conducted. 90% believed that clinical research is generally safe, but 44.9% reported that clinical trials are rarely considered as an option when discussion treatments or medications with their physician. Perhaps unsurprisingly, clinical trial participation was perceived as inconvenient and burdensome; 49% of respondents expressed that their clinical trial participation disrupted their daily routine.

Clearly, there is a lot of work to be done in terms of normalising trial participation, and improving trial design to minimise burden and/or disruption for participants. Read the full paper here.

Webinar: Health Care Improvement Scotland’s QI Connect Global WebEx Series presents ‘Too much medicine… winding back the harms of medical excess’ with Fiona Godlee
Fiona Godlee is Editor-in-Chief of the BMJ, she’s a qualified doctor and hugely intelligent and inspirational woman. I’ve seen her speak a few times, and each time I’ve been left feeling galvanised to do something to help solve the problems

she’s highlighted. She’s spoken at length about the harms of having ‘too much medicine’, and whilst at the BMJ she’s been heavily involved in their Too Much Medicine campaign. This webinar promises to be an interesting look at the problem of medical excess, and hopefully some ideas on how we can prevent the continuation of over-medicalisation.

This webinar takes place on October 31st 4-5pm (UK time), and you can register for free here.

Opinion: How to fulfil China’s potential for carrying out clinical trials

Some researchers believe that China has the potential to become one of the world’s most favoured sites for performing clinical trials. Largely, this is because China is home to ~20% of the world’s population, as well as a pattern of morbidity and mortality that is increasingly similar to Western countries – it has been suggested that doing trials in China could solve the recruitment issues we see so often in trials conducted elsewhere. Currently, China has 32 national centres for clinical medicine research, and has formed a collaborative innovation network of more than 2100 medical institutions in 260 cities. Another attraction is that – for the time being at least – trials conducted in China cost half or less compared to those conducted in Europe and North America because it has larger numbers of medical staff and a lower cost base.

That said, moving all trials to China isn’t a viable option right now; the country’s trial experience is very much in its infancy, and it’s important that we ensure that trials are of a high quality. This article published in the BMJ provides some initial ideas of how the wider trials community can help to ensure that China is able to fulfil its potential for carrying out high quality clinical trials.

Publication Explainer: The PRioRiTy Study

Today I had a new publication come out – hoorah! Told you that all the effort I put towards my 2017 goals would pay off eventually 🙂 This is the second in my ‘Publication Explainer’ series, and there are at least another 2 that I already need to write, read the first one here. As I said in that post, these explainers are a place for me to answer 3 of the most common questions I’ve been asked by the people around me (usually my boyfriend, friends, or colleagues that haven’t been involved with the project).

This post focusses on the paper below: Identifying trial recruitment uncertainties using a James Lind Alliance Priority Setting Partnership – the PRioRiTy (Prioritising Recruitment in Randomised Trials) study. Read the full paper here.

Why prioritise research questions about recruitment to trials?

Research around recruitment strategies for randomised trials is super important – though it is the premise of my entire PhD project so I would say that. Recruitment to trials is difficult, and many trials (estimates differ but average around the 45-50% mark) fail to recruit enough participants to hit their targets. Targets are not just numbers plucked from thin air, they’re based on detailed calculations performed by trained Statisticians – target figures are designed to enable researchers and trialists to see real differences in the various arms of trials. If we don’t hit target, then results of the research could be vulnerable to something called a type 2 error – which is most simply explained by the image below; it’s a false negative, meaning that we could be telling people that an intervention is effective when it isn’t, or that it isn’t effective when it is.

Clearly, recruitment is as area that requires research, but because there is so much work to be done, we are at risk of being a bit everywhere (just to be clear, ‘being a bit everywhere’ is not the technical term for this…) when it comes to focussing and making substantial progress with improving the way we do research. Going through a formal prioritisation process for the squillions of research questions that surround the process of recruitment, will enable researchers to coordinate the research that they’re doing, plan more effectively, and work together to ensure that we are answering the questions that are most important to the various stakeholder groups involved.

How did the prioritisation process work?

The process of prioritisation that enabled this project to go ahead was a development with the James Lind Alliance – the JLA works with clinicians, patients and carers ensure that all voices are heard, and that prioritisation of research questions reflects the requirements of all of these groups. The James Lind Alliance works on the premise that:

  • addressing uncertainties about the effects of a treatment should become accepted as a routine part of clinical practice
  • patients, carers and clinicians should work together to agree which, among those uncertainties, matter most and deserve priority attention.

The prioritisation process begins with getting partners involved with the PRioRiTy project – this isn’t a project that can be done by one person!The stakeholders involved with this priority setting partnership were:

  • Members of the public who had been invited to participate in a randomised trial or participated in Trial Steering Committees (TSCs). They could be an individual or representing a patient organisation;
  • Front line clinical and research staff who were or had been involved in recruitment to randomised trials (e.g. postdoctoral researchers, clinicians, nurses, midwives, allied health professionals);
  • People who had established expertise in designing, conducting, analysing and reporting randomised trials (e.g. Principal Investigators/Chief Investigators);
  • People who are familiar with the trial methodology research landscape (e.g. funders, programme managers, network coordinators).

Once relevant stakeholders were identified, an initial survey with just 5 questions (below in Table 1 which is taken from the original paper) was developed and distributed to the stakeholders involved.

Responses were collated, organised, coded and analysed in order to generate a full list of research questions. This was a massive part of the work; 1,880 questions came from the 790 respondents to the initial survey. The figure below shows the process of whittling down this huge pile of questions to a manageable – and useful – top 20.

As you can see, this was an iterative process involving lots of people, views, questions – and work! I’ll just make it clear here – I was involved in a small part of this process, and the team working on the project was large; as I said before, with projects like this it’s important to involve people from lots of different backgrounds and with various levels/areas of expertise. The team was led by Prof Declan Devane and Dr Patricia Healy, both from NUI Galway, they kept the rest of us on track!

What next?

In terms of next steps for the team involved in the PRioRiTy project, it’s really important that we work to disseminate our results; after all, if no ones knows what the final list of prioritised questions is, then there was really no point in doing the project. So – with that in mind, here’s the final top 10!

To give these questions some context I wanted to talk through a few of them to go through my thoughts on what types of research may be required to answer them, and why they’re important.I’ll stick to the top 3 for this part:

Understanding how randomised trials can become part of routine care is, unsurprisingly, the top question from this entire project. Knowing how we can use clinical care pathways to ensure that patients are given the opportunity to take part in trials is a hugely important part of normalising trial recruitment, and spreading awareness of trials more generally. There is a tonne of research to be done in this area, and in my opinion, this question will need a diverse range of research angles and methods in order to answer it in a variety of ways.

This question is interesting – what information should trialists be giving to members of the public that are being invited to take part in trials? That seems like something we should have evidence for, but in actual fact we are working from hunches, experiences, and anecdote. I think this question will rightfully fuel a lot of research projects over the coming years, we need to be looking at what information potential participants want, as well as what they need form an ethical/regulatory stand point – at the moment I get the impression that we’re being driven by ethics committees and regulators, and we’re often putting in a lot of information that participants don’t want/need/find useful, because we feel it’s better to give them everything, rather than risk missing something out. I suspect that if we reduce the amount of information we provide, the understanding of that information would increase because participants are able to focus on specific pieces of information more effectively. I say that because I know that if I get a huge leaflet, I’m much more likely to avoid the entire thing because it looks overwhelming, or I don’t think I have time to get through all the information in front of me.

This question is one that I’ve been asked, and I myself have asked, numerous times over the course of my PhD. Public engagement and patient involvement are both areas of academic life that are getting increased focus; we know that involving patients and members of the public in our research can strengthen it, make the work we’re doing more relevant to the people that we’re doing it for, but could this involvement impact on recruitment rates too? I’m not sure, but I’m really interested to see the results of a few projects that are linked to this question that are currently ongoing – the PIRRIST study led by Dr Joanna Crocker is one I’ll be keeping an eye out for. The PIRRIST protocol was presented as a poster at a conference I went to in 2015, that information is published here if you’re interested in learning more.

Something to note

The appendix of the paper contains a full version of the table below, this provides details on the evidence that we already have available to us to help answer each of the top 10 questions. The top 3, which I’ve discussed above, have no evidence available – which really drives home the importance of a formal prioritisation process in highlighting where the gaps are in research evidence.

There is certainly a lot more work to be done on how we recruit participants into randomised trials – which is good for me as I want to stay in this field of research after my PhD, and hopefully get some of these questions answered over the course of my career!

My PhD Project in Detail

Last week I got a comment on one of my blog posts asking what my PhD project is about – I scrolled back through my blog and couldn’t find a post dedicated to explaining it (I’ve clearly been too busy banging on about women in STEM, public engagement, and clinical trials in general terms…), so here’s a blog post focussing on my PhD project to remedy the situation.

Project title

Making clinical trials more efficient: consolidating, communicating and improving knowledge of participant recruitment interventions

Where and when?

The University of Aberdeen’s Health Services Research Unit (HSRU), based with Trial Forge.

Study phases and objectives:

Phase 1: To consolidate existing information on participant recruitment into clinical trials.
This will involve completion of a systematic review of non-randomised evaluations of strategies to improve participant recruitment to RCTs (protocol is published here), involvement in updating the existing Cochrane review on randomised evaluations of strategies to improve participant recruitment to RCTs (the 2010 version is published here, and the update is coming!), and involvement with a new Cochrane review led by NUI Galway which will look at the factors that impact participants’ decisions regarding trial participation using a qualitative evidence synthesis (protocol is published here).

Phase 2: To investigate how best to present and distribute this information for the consumption of clinical trial teams. This phase will comprise of a semi-structured interview study with trial ‘recruiters’ (i.e. people who are actively involved in the process of identifying, approaching and recruiting participants to trials), and ‘designers’ (i.e. the people who are in a position to make decisions regarding the methods that a trial uses to recruit – e.g. the person who decides that using a Twitter post, newspaper article, or radio advert would be a good idea to attract participants to the trial), generation of multiple methods of presenting recruitment evidence, and user-testing of these methods using a think-aloud protocol.

Phase 3: To improve the current knowledge base through facilitation of work designed to fill gaps in evidence. To do this I will be producing protocols for a number of SWATs (studies within trials) specifically designed to fill gaps in knowledge found in the reviews that make up Phase 1 of the project. These protocols will be published on the SWAT repository, encouraging trial teams around the world to fill these gaps in our recruitment knowledge.

Clinical trials are at the core of evidence-based healthcare; because they randomise participants to each arm of the trial, they guard against selection bias and therefore offer the fairest way of evaluating healthcare interventions. In more basic terms, randomising participants to Group A and Group B, then you can make sure that you don’t end up with all of one type of participant (e.g. older people, younger people, more ill people, only one gender etc) in Group A, and none in Group B.

The recruitment of participants into clinical trials is difficult – lots of trials have problems with recruitment, and many require extensions to both time and budget as a result of these recruitment issues. In the worst cases, trials can be abandoned entirely because they can’t recruit enough participants; this causes huge waste. What is surprising then, is that the process of recruitment has very little evidence behind it. Largely, we’re relying on gut instinct, experience, and hope.. none of which seem to be working all that well.

My project aims to begin to tackle the problem of trial inefficiency by getting to grips with how participants are recruited into trials, ultimately aiming to improve recruitment methods in order to alleviate recruitment problems in trials on a global scale.

Why this project?

As part of my undergraduate degree, I did an industrial placement year – I swapped student life for a year working in recruitment. I worked for a recruitment agency that supported clinical research companies in industry to recruit staff (Principal Investigators, Research Nurses, Project Managers etc). Essentially, I spent a lot of time on LinkedIn, a lot of time on the ‘phone, and a lot of time annoying people by calling them after seeing their CV on job sites.. Anyway, as part of that role I set up a bank of Research Nurses for an international clinical research organisation. I hired 15 nurses who would do ad hoc shifts when the trial sites needed some extra pairs of hands. I really enjoyed that part of the job, it was nice to get someone from application through to being hired, and to go on that person’s journey alongside them. What wasn’t so nice though, was when those Research Nurses that I had hired started to get turned away from work. This was because the trials that they were working on didn’t have enough participants – no participants, means no data collection, and therefore no need for my Research Nurses.

When I went back to Uni to finish my degree, I was still searching for ways to recruit participants effectively – I didn’t find much, other than an advertisement for a PhD. I applied, interviewed, and was offered the post the same day. I started a month after graduating from my Undergrad, and I’m still working out how on Earth to recruit participants to trials.. it looks like it might be a career-length question, which is totally fine by me 🙂