Really important to keep patients at the centre of patient - PDF document

Really important to keep patients at the centre of patient recruitment Not necessarily always the case Word cloud created from 2000 word article on Patient Recruitment and Retention Quick overview of our trials: We have a drug called nitisinone It reduces the acid which causes joint damage in Alkaptonuria (AKU) Don't currently have enough proof that this translates to reduced joint damage/other symptoms or improved Quality of Life Conducting 3 studies

First study: SONIA 1 or Suitability of Nitsinone in Alkaptonuria 1 4 week study involving 40 patients. Split into 5 groups of 8, each receiving different dose of nitisinone Determine best dose to use for SONIA 2 Suitability of Nitisinone in Alkaptonuria 2 4 year study involving 140 patients 2 groups of 70 patients. Show whether nitisinone is effective in treating AKU

Sub clinical ochronosis features in alkaptonuria Observational study – 32 patients from 8 different age groups. Hoping to show how AKU changes with age which will give indication of when to begin treatment. Patient Recruitment takes up to 30% of the clinical development timeline Source: Bairu, M., and Weiner, M., 2013. Global Clinical Trials for Alzheimer’s Disease: Design, Implementation and Standardization , San Diego: Academic Press. p207 Patient Recruitment problems cause delays in 90% of clinical trials Source: “Online recruitment is streamlining clinical trials” Datamonitor, July 2008. http://www.datamonitor.com/store/News/onlin e_recruitment_is_streamlining_clinical_trials?pr oductid=62E17CB0-F4C4-4774-A3A2- 598600B85247 And these figures are from all trials – not rare disease trials

We know of around 1000 patients worldwide although the actual number is probably higher We need around 150 patients to take part in our studies This becomes more challenging when our recruitment area is limited almost entirely to the EU because of restrictions from our funder (EC), cost, insurance and visa requirements. Also can't recruit those already taking the drug off-label: this rules out all English and Scottish patients. Pool of patients reduced further by inclusion/exclusion criteria Don't just want challenges – we also have solutions Existing relationships were a good place to start: The AKU Society began in 2003 and has a lot of contacts. The DevelopAKUre consortium consists of 13 organisations with their own contacts

Went through global database and contacted patients who might be interested. Patients who knew about the trial also came to us Spread the word to known clinicians and scientists: asked them to tell colleagues etc. Sister Societies have been extremely helpful. When we began had societies in France, Germany, Italy and the Netherlands. Now also have societies in Belgium and Slovakia. Help to organise local patient meetings – always better to meet face to face with interested patients. Also help with considerable language barrier Existing relationships have most buy in. They know the history and they often stand to benefit if the trial is successful. Really want us to succeed.

AKU Society already had a very active online presence – built on this for patient recruitment 2013 Survey found 46% of clinical research participants found information about their study online. Increased from 25% in 2004. Source: CISCRP, Report on Clinical Trial Information Seekers, 2013 Perceptions & Insights Study: p2, 2013 Built a separate microsite for the DevelopAKUre project separate from the main AKU Society website Launched in June 2013: 120 visits in the first month. Increased by 486% in next 5 months. Every page has a 'Register your interest' box. Details come straight to me and I can reply with more information. Have had 40+ entries so far – a lot for a disease as rare as AKU.

In addition to website, have also used Facebook, Twitter, PatientsLikeMe and Rare Connect. Open discussions with patients. Often find patients who cannot take part cheering on patients who are taking part 14/15 patients who took part in SONIA 1 at the Liverpool test centre were from existing relationships or online presence. Not enough for our second trial – still needed many more patients Emailed hundreds of healthcare specialists and national groups Fax campaign to thousands of hospitals and medical centres Set up Google alerts so we are notified when alkaptonuria is mentioned on the internet. Contact all authors of new research papers or case studies of AKU patients.

Finding patients is just the beginning. Have to keep patients on board from initial contact to enrolment and then for four years of the trial. Important to balance recruitment and retention. Can be tempting to just focus on the numbers of recruitment and to forget you really need patients who are going to stick it out for the whole trial. E.g. don't want patients who are highly likely to drop out if they find themselves in the non- treatment group Need to get patient input on trial design. For example many patients were worried about having an ear biopsy which is the most invasive assessment in SONIA 2. Ear biopsy was made optional so patients weren't put off taking part. Also need to explain things to patients and treat them like adults. Even though the ear biopsy has been made optional – most patients have agreed to have it once we've explained why it's important. Put a lot of effort into explaining the need for a non-treatment/control group.

Part of providing a constant stream of information for patients. Includes fortnightly blogs on the microsite, newsletters, patient meetings and direct contact. Also organised 2 webinars led by the lead investigator on the trial so patients could ask him questions directly. Encourage patients to ask any questions they have. 68% participants say regular updates influenced their decision to participate in a trial. Source: CISCRP, Report on Study Participant Experiences, 2013 Perceptions & Insights Study: p2, 2013 Taking part in a trial is stressful enough without additional problems. Streamlined expenses reimbursement. Raised additional money to fund carers. 38% of trial dropouts say they found the experience stressful compared with 16% of those who remained in the study until the end Source: CISCRP, Report on Ineligible Participants and Those Who Terminate Participating Early: p3, 2013

Very important to form relationships with patients. Happy if a patient understands everything about the trial. Even happier if I know they enjoyed their recent holiday or if they've been practicing their English with a visiting friend. Relationships with other patients also very important. 61% said feeling part of a community was an important part of deciding to take part in a trial. Source: CISCRP, Report on Study Participant Experiences, 2013 Perceptions & Insights Study: p2, 2013 Some of our patients who took part in SONIA 1. Forming relationships and having a sense of community can help with recruitment – patient recently found out we still need to recruit another 10 patients and volunteered to contact the patients he knew who weren't taking part to tell them about his experience. AKU patients are so scattered, a trial may be the first time they get to meet another AKU patient. Quote from a patient who took part in a previous trial about how she felt when she met another patient.

Cannot repeat enough the need to focus on patients Take home: Be relentless about finding patients. Don't worry if a doctor gets annoyed because 3 different people have asked him whether he knows any AKU patients. Keep getting information out to patients and clinicians. Keep it personal.