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Background: Pharmacogenomics (PGx) is the use of Deoxyribonucleic Acid (DNA) to predict an individuals' response to a drug. Through the lower cost of DNA sequencing and advances in genomic medicine, PGx testing is a viable and valuable tool in improving medicines optimisation for patients. Over recent years, the role of the community pharmacist in England has evolved from dispensing medicines to delivering increasingly complex pharmacy services. In addition, community pharmacy is accessible and convenient for patients, and therefore potentially an appropriate setting for this testing service. Whilst in some parts of the world, community pharmacists have begun offering PGx testing, there is no evidence of any activity in England. There is therefore a research gap in knowledge to establish if this service could be implemented in the culture and context of the healthcare infrastructure and system in England, which differs somewhat from other countries. Method: The principles of co-design were deployed following three sequential phases using action-orientated frameworks and tools. In Phase One, three focus groups were conducted with community pharmacists (n= 10), prescribers (General Practitioners) (n= 8) and patients (n=8) to identify the barriers and enablers to implementing a community pharmacy based PGx service in England. The focus groups were recorded, transcribed and thematically analysed. In Phase Two, barriers and enablers from Phase One were mapped onto the Theoretical Domains Framework (TDF) followed by use of the Theory and Techniques Tool (TATT) to link the identified TDF domain with corresponding Behaviour Change Techniques (BCTs). A consensus questionnaire followed by a Nominal Group Technique workshop were used to facilitate community pharmacists (n=11) selecting their preferred BCTs to include in a service specification. Finally, in Phase Three, a draft service specification was developed, and a joint participant (n=12) consensus panel was convened for critical comment. The service specification was refined based on the feedback. Results: Five barrier and enabler themes were developed in Phase One: (1) In-principle receptiveness, (2) Appreciation of the benefits, (3) Lack of implementation resources (4) Ambiguity about implications for implementation and (5) Interprofessional relationship challenges. In Phase Two, the qualitative data from the pharmacist focus group were mapped onto six TDF domains: Knowledge, Skills, Social/ professional role and identity, Optimism, Beliefs about Consequences, and Environmental context and resources. Forty-six BCTs were identified using the TATT, of which nine BCTs were selected by the target audience: Review outcome goal(s) (1.7), Information about emotional consequences (5.6), Pros and Cons (9.2), Social support (Practical) (3.2), Feedback on behaviour (2.2), Instruction on how to perform behaviour (4.1), Demonstration of the behaviour (6.1), Credible source (9.1) and Adding objects to the environment (12.5). Finally, in Phase Three, the draft service specification was produced, and progressed into the final version following critical feedback from the mixed participant consensus panel. Conclusion: The co-design methodology using action-orientated frameworks and tools has resulted in the production of a novel service specification for implementation of a PGx community pharmacy testing service in England to fill a gap in research knowledge. This can now be used to implement the service and further research should be carried out to evaluate the service post implementation.

Introduction: Six phase III randomised trials established the effectiveness of chemoradiotherapy as primary treatment for squamous cell carcinoma of the anus (SCCA) and over the last 30 years survival has progressively improved. However, variations in trial outcome reporting have limited between-study comparisons and hindered evidence synthesis, and despite considerable treatment-related morbidity no trial has comprehensively quantified late toxicity or quality of life. This thesis proposed to address these issues through the development of a core outcomes set (COS) “an agreed, standardised set of outcomes to be measured and reported, as a minimum, in all trials in a particular health area”. The project involved three phases described in subsequent chapters (i) outcome long-list generation through systematic review and semi-structured patient interviews; (ii) Delphi survey and (iii) face-to-face consensus meeting. Chapter 3 & 4: Systematic review (published in Colorectal Disease) identified 1243 outcomes from 101 trials and observational studies of chemoradiotherapy for SCCA. No outcome was reported in all trials and over half of outcomes were reported in less than five percent of studies. In 54% of studies no definition was provided. Reported outcomes were predominantly in the survival and disease activity domains; life impact and toxicity outcomes were reported infrequently. No core set of outcomes could be identified from the existing literature. Semi-structured interviews with 19 patients identified 56 outcomes including eight not identified in the systematic review. Thematic analysis identified how outcomes impact the lives of patients, including a novel description of symptom clusters in SCCA. Chapter 5: The long-list of outcomes generated from chapter 3 and 4 was used to populate a Delphi questionnaire. One hundred and forty-nine participants from 11 countries (patients 55; HCPs 94) completed both rounds of the Delphi. Twenty-three HCPs and 13 patients from four countries participated in the face to face consensus meeting where after discussion and anonymous voting the final COS of 19 outcomes was agreed. These were treatment response, local failure, regional failure, distant failure, disease progression, salvage surgery, overall survival, cancer-specific survival, disease-free survival, metastasis-free survival, progression-free survival, anal incontinence, faecal urgency, pelvic fistula, stoma, skin loss, physical function, sexual function, and health-related QoL (accepted for publication in Lancet Gastroenterology and Hepatology). Chapter 6: Three secondary methodological research questions were addressed. Systematic review of outcome domains in cancer COS informed the domain framework for the CORMAC project and contributed to the development of the outcome taxonomy recommended by COMET. Comparison of outcomes included in COS for site-specific cancers to those included in COS for cancer in general identified no emergent COS for cancer in general. A novel study using a simulated Delphi and think-aloud process demonstrated patients had good understanding of histograms in this context. Discussion: The findings in Chapter 3 and 4 demonstrate the lack of existing consensus on optimal trial outcomes in SCCA and that outcomes prioritized by patients are under-represented in existing studies. A core outcome set for trials of chemoradiotherapy for SCCA has been agreed through a methodologically rigorous and transparent consensus process involving key stakeholders. The steps required for implementation including agreement of recommend definitions and measurement instruments for outcomes in the COS are described.