Clinical Research Overview By Lydia Harris Hilary Campbell

Clinical Research Overview By Lydia Harris, Hilary Campbell and Paula Strider

Research Background

Why do we do Research? • Clinicians • Allows us to improved quality of care now and identify new treatments for future generations • Patients • Opens up a new set of treatment options • Patients feel like they are giving something back • Patients have a positive feeling about being in a trial • Patients feel more in control of their treatment • Patients have a greater understanding of what is being done to them and why • Patients in trials have better outcomes

Why do we do Research? • A recent study indicates that research-active NHS Trusts have better patient outcomes? • The study showed that patients cared for in research- active acute NHS Trusts have better outcomes. The results of the research, published in an international, peer-reviewed journal, demonstrated a direct association between higher levels of research-activity and lower rates of patient mortality following emergency admissions http: //www. crn. nihr. ac. uk/blog/news/research-active-trustshave-better-patient-outcomes-study-shows/

National Context • National Institute of Health Research (NIHR) - aim to make the NHS a global leader in clinical research, part of the health and wealth agenda • NHS Constitution states that every patient has the right to be offered to be part of clinical research • Currently every NHS Trust in England (240) are research active • In 2015/2016 605, 596 people took part in clinical research studies in England • At York Teaching Hospital 4552 people took part in clinical research studies in 2015/2016

NIHR League Table Number of Studies Currently Recruiting Patients 15/16 Position Nationally Newcastle 514 1 st Guys & St Thomas’s 494 2 nd Leeds 477 3 rd Sheffield 371 8 th Hull 181 26 th Bradford 180 27 th York 135 39 th

NIHR League Table Number of Participants recruited into Clinical Trials 14/15 Position Nationally Guys & St Thomas’s 23187 1 st Southampton 20759 2 nd Oxford 17827 3 rd Leeds 12368 10 th Sheffield 7786 17 th Bradford 5416 25 th Harrogate 4616 32 nd Hull 3706 35 th York 3203 45 th

Local Context • Part of Clinical Research Network (CRN) for Yorkshire & Humber with 22 partner organisations • We have 10% of the national population in our region so we are excepted to get 10% of the NIHR national target for patients recruited into a clinical trial. • Yorkshire & Humber target is 65, 000 accruals (patients consented into a clinical trials) • The Trust target set by the CRN as a contribution towards the regional target for 2016/17 is 3859 accruals.

Current Performance The total for August is 229, The running total for this year is 1257 4000 3500 3000 2500 Target 2000 17/18 1500 16/17 1000 15/16 500 0 Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar 165 studies currently open of which 8% commercial studies

Income Associated with Research • 3 main ways to generate income from research • Grant funded research • Commercial research income • CRN allocation associated with our accruals • These monies currently support research nurse and Clinical Trials Assistance salaries as well as our support services. • The Trust also supports many research posts (for example the R&D Dept), many of which are permanent positions.

Types of Research

Types of Research Treatment Screening/Diagnostic Genetics Quality of life

Treatment research (also called “clinical trials”) generally involves an intervention such as medication, psychotherapy, new devices, or new approaches to surgery or radiation therapy.

Screening/Diagnostic The practice of looking for better ways to identify a particular disorder or condition. Screening research aims to find the best ways to detect certain disorders or health conditions.

Genetics Research in this area may explore ways in which a person’s genes make him or her more or less likely to develop a disorder. This may lead to development of tailor-made treatments based on a patient’s genetic make-up.

Quality of Life Also known as “supportive care, ” this research explores ways to improve comfort and the quality of life for individuals with a chronic illness.

Commercial Research The life sciences industry is • Pivotal to the UK economy • An essential source of revenue for the NHS • A primary source of innovation and change for healthcare

Other! Not all research is invasive or involves seeing a Doctor • Data- Yorkshire Health Study – meta analysis why not complete one today! • Shews for Crews – staff comparing non slip shoes to normal footwear

Questions? Head of R&D Research & Development 01904 726606 07702816606 Lydia. harris@york. nhs. uk

The Role of a Research Nurse Hilary Campbell Lead Research Nurse

THE ROLE OF THE RESEARCH NURSE

P Values? Help. . Hazard Ratios! Confidence intervals Confidence what’s? Statistics (yawn)

WHERE DO WE START?

Expressions of interest ↓ Feasibility ↓ Approvals ↓ Green light ↓ First Patient Recruited

Chemo Nurses Sponsors MDT Labs Risk & Legal Consultants Research Nurse Histo Trials Radiology DM/ FM MRI Pharmacy Governance R&D

Screening for patients ↓ Confirm Eligibility ↓ Approach Patient to Discuss Trial ↓ Consent ↓ Protocol led process

Consent Advocacy HRU Questions! Monitor Safety of trial participants MHRA Giving Drugs Qo. L Blood Samples Prescriptions Amendments Follow up Communication Side effects Appointments Referrals Data Queries

Documentation

AND AFTER ALL THAT… Close out visits Results for patients Archiving Ongoing safety reports

GETTING THE MESSAGE OUT THERE…

WHY? • Making patients & NHS better • Increased opportunities for patients to access novel treatment • Provide the best advice and treatments for people • Share knowledge and learning • Improve patient care • Generate an income for the Trust from Commercial Research

Putting the patient at the center of everything we do Respect - Safety- Quality

• The role of the research nurse is highly rewarding, with many opportunities to learn and develop new skills • It is largely autonomous and patient–centred • A long relationship is often developed with patients and relatives during the patients trial journey • Both the nurse and the study participant can take. pride in the role they play in future treatments and technologies

Trust Research Staff • • • • Oncology/Haematology at York and Scarborough Renal Rheumatology Ophthalmology Diabetes Cystic Fibrosis Cardiology Obs & Gynae Gastroenterology Stroke Paediatrics Neurology Sexual Health Dermatology Generic team at York and Scarborough

TEAM WORK

Snowflakes are one of nature’s most fragile things……

……. . but look at what they can do when they stick together… Vesta Kelly

How research makes a difference to patients: A research nurse perspective Paula Strider senior research nurse cancer research team

• Introduction • Combining clinical research & nursing • What do we do? • Why do we do it? • Safe. Her, KAMILLA & KAITLIN • None treatment trials • Bridging the Age Gap • Home grown research • Clever new drug therapies

6 c’s Care Compassion Courage Communication Commitment Competence Caring about what we do Respecting and valuing each other Listening in order to improve Always doing what we can to be helpful Research Patient/ Participant Research Nurse/Research Staff/Hospital staff NMC Code of professional conduct Good Clinical Practice & Regulations & Ethics

cannulation MDT Informed consent Challenging MHRA Consultants/PI’s Screening Phlebotomy Ward staff Meetings presentations reports embed in practice TEAM WORK radiology Drug administration SOP’ s Research Teams trial monitors consent Point of contact Doctors collaboration teleconferences Sub studies Data queries randomisation organisation Attention to detail Surgeons webinars patient follow ups Clinic staff questionnaires Site file pathology support dynamic PROTOCOLS Site file pharmacy amendments universities Pharmaceutical companies

A true privilege To change the patient journey to improve outcomes: Paul I love primary care research, it’s such a challenge! Simon Paula I love being a research nurse as it is extremely rewarding knowing that I am helping to improve treatments and care for patients in the future: Kate Today’s treatment is yesterday’s research; today’s research is tomorrow’s treatment for our patients: Tania “Research, it’s not just an For the benefit of acronym; it changes practice and future generations: improves the quality and John standards of care our patients receive” : Claire Clinical research extends patient choices and sometimes gives a choice when previously there was none: Kate ‘The cutting edge’ New treatments may prolong life: Kay • Innovation • Best research for best practice: Becky

Safe. Her A PHASE III PROSPECTIVE, TWO-COHORT NON RANDOMIZED, MULTI-CENTRE, MULTINATIONAL, OPEN LABEL STUDY TO ASSESS THE SAFETY OF ASSISTED AND SELF-ADMINISTERED SUBCUTANEOUS TRASTUZUMAB AS THERAPY IN PATIENTS WITH OPERABLE HER 2 -POSITIVE EARLY BREAST CANCER Trastuzumab in breast cancer • Standard treatment HER 2 +ve • Commenced along side chemotherapy • Usually 18 cycles (one year) • Originally given Intravenously - 60 -90 minute infusion Recombinant human hyaluronidase (r. Hu. PH 20) • 5 minute subcutaneous injection • Reduces viscosity of extracellular matrix of hypodermis • Improves delivery subcutaneous drugs • Increases volume of drug that can be given

KAMILLA A MULTICENTER, SINGLE ARM STUDY OF TRASTUZUMAB EMTANSINE (T-DM 1) IN HER 2 POSITIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER PATIENTS WHO HAVE RECEIVED PRIOR ANTI-HER 2 AND CHEMOTHERAPY-BASED TREATMENT KAITLIN A RANDOMIZED, MULTICENTER, OPEN-LABEL, PHASE III TRIAL COMPARING TRASTUZUMAB PLUS PERTUZUMAB PLUS A TAXANE FOLLOWING ANTHRACYCLINES VERSUS TRASTUZUMAB EMTANSINE PLUS PERTUZUMAB FOLLOWING ANTHRACYCLINES AS ADJUVANT THERAPY IN PATIENTS WITH OPERABLE HER 2 -POSITIVE PRIMARY BREAST CANCER

Trastuzumab. Emtansine T-DM 1

Not all trials involve drugs • Observational • Quality of Life • None interventional • Data collection • Sample collection • Genetic

Bridging the Age Gap in Breast Cancer: Improving outcomes for older women. An observational study to help ensure older women get the best treatment when they have breast cancer EMPRESS Cancer diagnosis via Emergency Presentation: a case-control study Lung and colorectal cancers: comparison of outcomes from E. P vs. 2 week wait HORIZONS: a cohort study to explore recovery of health and well-being in adults diagnosed with cancer. HORIZONS: understanding the impact of cancer diagnosis and treatment on everyday life: Breast, Gynaecological and Lymphoma cancers.

Bridging the Age Gap in Breast Cancer: Improving outcomes for older women. An observational study to help ensure older women get the best treatment when they have breast cancer • UK population is ageing • average life expectancy increasing • fitness of older people increasing • Health technologies rapidly advancing • improvements in the survivability of interventions such as surgery • People over 70 still considered ‘elderly’ • Age related practice varies

BTAG Decision making aid for clinician and patient

Home Grown Research Fast track faecal calprotectin Can a stool test (calprotectin or blood) help predict for bowel disease? • Chief investigator: Dr James Turvill Consultant Gastroenterologist York Hospital • 2 stool samples tested for biomarkers • Can indicate Inflammatory bowel disease (IBD), cancer or infection • 96% effective • Test costs £ 35 • Save money as will reduce number of hospital referrals

Clever new drugs RIBOCICLIB Ribociclib inhibits CDK 4/6 ER/Pg. R/AR MAPKs STATs • Inhibitor of cyclin-dependent kinase (CDK) 4 and 6. • These CDK 4 and 6 kinases play a crucial role in signalling pathways which lead to cell cycle progression and cellular proliferation. • Stops cell cycle from progressing into S-phase • Halts proliferation Wnt/b-catenin Pl 3 K/AKT/m. TOR NF-k. B p 21 Cyclin D p 53 CDK 4/6 p 16 P Rb Rb E 2 F M Gene transcription E 2 F G 0 G 2 G 1/S checkpoint S

New Trials: Comp. LEEment -1, Ear. LEE-2 : RIBOCICLIB An open-label, multicenter, Phase IIIb study to assess the safety and efficacy of ribociclib (LEE 011) in combination with letrozole for the treatment of men and pre/postmenopausal women with hormone receptor-positive (HR+), HER 2 -negative (HER 2–) advanced breast cancer (ABC) with no prior hormonal therapy for advanced disease Ear. LEE-1: A phase III, multicentre, randomized, double-blind, placebo controlled study to evaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER 2 negative, high risk early breast cancer Ear. LEE-2: A phase III, multicentre, randomized, double-blind, placebo controlled study to evaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER 2 negative, intermediate risk early breast cancer

IImmunotherapy • Checkpoint inhibitor • Immunotherapy • Targets PD-L 1 protein on cancer cells • Inhibits cancer cells from tricking the immune system • Immune system recognises and ATEZOLIZUMAB destroys cancer cells

Urothelial Imvigor 130: A PHASE III, MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB (ANTI−PD-L 1 ANTIBODY) AS MONOTHERAPY AND IN COMBINATION WITH PLATINUM-BASED CHEMOTHERAPY IN PATIENTS WITH UNTREATED LOCALLY ADVANCED OR METASTATIC UROTHELIAL CARCINOMA Lung PS 2: A PHASE III, OPEN-LABEL, MULTICENTER, RANDOMIZED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF ATEZOLIZUMAB COMPARED WITH CHEMOTHERAPY IN PATIENTS WITH TREATMENTNAÏVE ADVANCED OR RECURRENT (STAGE IIIB NOT AMENABLE FOR MULTIMODALITY TREATMENT) OR METASTATIC (STAGE IV) NON-SMALL CELL LUNG CANCER WHO ARE DEEMED UNSUITABLE FOR PLATINUM-CONTAINING THERAPY

• Challenging • Exciting • Demanding • Varied • Rewarding • A great privilege • Any Questions?