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Where is

Real World Evidence?Finding sources for the

outcomes that matter

SVMPharma LtdLandmark HouseStation RoadHook, HampshireRG27 9HA

Patient level data access in the

NHS: Generating positive outcomes

through Real World Evidence

Real world evidence (RWE) is data used forhealthcare decision making that are notcollected in conventional randomisedcontrolled trials (RCTs). As such, sources ofreal world data (RWD) are varied andplentiful. Classically this includes clinicaland economic data reported by patientregistries, claims databases, electronichealth records, patient-reported outcomesand literature reviews. With advances intechnology and data handling, the sourcesand storage of this data growsexponentially.

We examine the conventional sources ofRWD and also evaluate their strengths andweaknesses, and when you may considerutilising each data source for RWE.

Where is Real World Data?Real World Data can be collected from a

myriad of sources, with their selection

largely dependent on the needs for data

collection. Although these requirements will

drive the specific sources of data collection,

a study should also be designed around

understanding where this data lies and the

benefits and limitations around each.

Real world evidence sources can be broadly

classified by outcome:[1]

CLINICAL : Biological measures of morbidity

and mortality. RCTs collect clinical data, but

clinical data can also be found in many

other sources such as patient registries or

observational databases.

ECONOMIC : Estimated measure of medical

and non-medical resources used or saved.

Such data are used to project the expected

cost of an intervention in the real world.

PATIENT REPORTED : Any measure or report

coming directly from the patient. The term

encompasses any report directly from

patients about a health condition and its

treatment including symptoms, treatment

satisfaction, preference and adherence.

2

Where is Real World Evidence? Finding sources for the outcomes

that matter

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Registries Supplements to RCTs

Non-RCT studies

Claims databases HES

data

Healthsurveys

Patient notes

Prescription data

Clinical

Economic

Patientreported

Social media

Sources of Real World Data

Supplements to RCTsTo provide additional data alongside standardRCTs, researchers often gather information onvariables such as patient recorded outcomes,medical resource use and costs.[2]

Supplementing trial data with additionalobservations extends RCTs into the real worldand creates additional value on treatmentpatterns for common events. It is often morepractical to collect data alongside a trial than tofund a stand-alone study and an economicevaluation can benefit from the experimentaldesign that maximises the trial’s validity.Limitations to such data are in line with those ofRCTs; their primary aim is to measure a keyclinical efficacy endpoint in a carefully limitedpopulation and clinical setting. Being tied toRCTs, there is also a lack of focus on economicdata and hence are of limited use in measuringassociated resource utilisation and costs, whichare often driven by protocol. Furthermore, RCTsare generally conducted over a shorter timeframe than what is relevant for determining theoverall clinical and economic impact of anintervention.[2]

Non-RCT studiesSometimes called ‘large simple trials’ or‘practical or pragmatic clinical trials’, thesestudies are similar to RCTs in that they involveprospective, randomised assignment but areaimed at larger, more diverse cohorts and so areoften more generalisable to real worldpopulations.Unlike RCTs, their focus is on obtaining policyrelevant outcomes such as costs and cost-effectiveness. Patients more at risk for adverseevents are also less likely to be excluded fromthe trial. However, the large size of a practicalclinical trial increases the cost of datacollection.

Claims databases and prescription dataAdministrative data (typically retrospective orreal time, if possible) are collected primarily foreconomic data (e.g. reimbursement), but cancontain some clinical diagnosis and procedureuse with detailed information on charges.Claims or insurance databases lend themselvesto retrospective longitudinal and cross-sectionalanalyses of clinical and economic outcomes atpatient, group, or population levels. Suchanalyses can be performed at low overall costand in a short period of time.Data on drug prescribing is another source ofadministrative data that can generate RWEinsights. Observing this type of data can provideinformation on prescription rates andcharacteristics of patients for specified drugs.

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Case study: The Salford Lung StudyThe Salford Lung studies were the world’sfirst Phase III pragmatic randomised clinicaltrials of a novel drug therapy.The study GSK sponsoredstudy from Salford, UKcompared the use of once aday inhaled corticosteroidagainst normal standard ofcare for COPD and asthmapatients. The trial tested both clinicaleffectiveness of treatments and their impacton 2802 patients’ ability to adhere andrealise long term benefit.[3]

Prescription rates and patient characteristicswere

Case study: RWE on prescribing of SGLT2 inhibitors

were monitored as sodium glucosecotransporter 2 (SGLT2) inhibitorsmoved from secondary to primarycare in the UK. A study of 34,278patients revealed that prescribingrates in women were lower than in RCTs,suggested to be due to concerns regardingincreased risk of infection.[4]

Sources of Real World Data

RegistriesDisease or patient registries are collections ofdata related to patients with specific diagnoses,conditions or procedures. Registries can collectclinical, economic, and patient reportedinformation, and are increasingly relying onreal-time data capture.Registries typically include a larger and morediverse group of patients than what is generallystudied in phase III RCTs, therefore they betterreflect real world patients, managementpractices, and outcomes. Patients are oftenfollowed over an extended timeframe, allowingfor an assessment of longer-term outcomes.However registries may only collect an overviewor annual reviews of drug prescribing, diseasemarkers, hospitalisations etc. and are oftenaggregated datasets, therefore not providingthe patient level data of patient chart reviews.[1]

Hospital Episode Statistics (HES) dataHES data is a data warehouse containing detailsof all admissions, outpatient appointments andA&E attendances at NHS hospitals in England.HES benefits include the monitoring of trendsand patterns in NHS hospital activity,assessment of effective delivery of care andprovision of national indicators of clinicalquality.[6]

Electronic medical health records and patient case notes review

Electronic health records and othertechnologies capturing real-time, patient levelclinical treatment and outcomes are importantsources for RWE. However not all healthcaresystems yet support EHRs. With the appropriateapprovals, it is also possible to collect patientlevel clinical data from written (non-electronic)patient chart notes. These RWD sources allowfor collection of a patients’ complete treatmenthistory, and so allows for generation of a richdata set and means standard of care and realworld clinical practices can be easily evaluated.

Social mediaResearchers WEB-RADR, in collaboration withthe Innovative Medicines Initiative work todetect new drug side effects by mining publiclyavailable web and social media content. WEB-RADR is also developing a mobile app forpatients and HCPs to report adverse events,similar to the already available Yellow Card appreleased by the UK’s MHRA.[5,7]

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EU initiatives to increase use of RWEThe European Commission has outlined several initiatives to increase the utility of RWE,including patient registries and electronic health records.

A number of EU initiatives promote the use and accessibility ofelectronic health records to support RWE across member states.PARENT Joint Action supports development of new, and use ofexisting, disease registries for widespread, unified use andmethodology to ensure wider downstream applicability.[5]

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1. ISPOR Real World Data Taskforce Using Real World Data for Coverage and Payment Decisions: The ISPOR Real World Data Task Force Report. 2016. Available from http://www.ispor.org/workpaper/rwd_tf/rwtfmanuscript.pdfAccessed September 2016.

2. O’Sullivan., A. K. et al. Collection of Health-Economic Data Alongside Clinical Trials: Is There a Future for Piggyback Evaluations? 2005. Value in Health. 8;1, 67-79.

3. GSK. Salford Lung Study results show COPD patients treated with Relvar Ellipta achieve superior reduction in exacerbations compared with ‘usual care’. 2016. Available from http://www.gsk.com/en-gb/media/press-releases/2016/salford-lung-study-results-show-copd-patients-treated-with-relvar-ellipta-achieve-superior-reduction-in-exacerbations-compared-with-usual-care/ Accessed September 2016.

4. Mcgovern, A. P. et al. Real-world evidence on prescribing trends in sodium glucose cotransporter 2 inhibitors in UK primary care. 2016. Diabetic Medicine. 33(S1):165.

5. European Medicines Agency. Update on Real World Evidence Data Collection. 2016. Available from http://ec.europa.eu/health/files/committee/stamp/2016-03_stamp4/4_real_world_evidence_background_paper.pdf Accessed September 2016.

6. National Health Service digital Hospital Episode Statistics. 2016. Available from http://digital.nhs.uk/hes Accessed September 2016.

7. Medicines and Healthcare products Regulatory Agency. Digital evolution for ground-breaking Yellow Card scheme. 2015. Available from https://www.gov.uk/government/news/digital-evolution-for-ground-breaking-yellow-card-scheme Accessed September 2016.

SVMPharma is an innovative strategic consultancy, specialising in Real World Evidence (RWE) for thepharmaceutical industry. SVMPharma generates RWE within UK and Europe through bespoke online RealWorld Treatment Evaluators, leading to successful health technology appraisal (HTA) submissions. Clinicaltrial programmes do not reflect real-world clinical practice and outcomes, RWE supplements and enhancesclinical datasets. SVMPharma’s specialist teams focus on delivering the outcomes that matter to your brand.SVMPharma also provides Global RWE, Patient Real World Outcomes, and Big Data Analytics.

To find out more call +44 (0) 1256 962 220

Establishing what is ‘must have’ vs. ‘nice to know’ data is essential when planning RWE and canhelp choose a relevant source for your RWE data that best meets your needs. Combiningdifferent data sources can provide a more diverse set of observations and show benefit for yourbrand.

SVMPharma is a RWE agency with experience of working on successful HTA resubmissions for NICE and SMC that can help gather the right RWE data and ease the RWE process to ensure

your best chance of gaining positive HTA submissions.

Health surveysHealth surveys are designed to collectdescriptions of health status and well being,health care utilisation, treatment patterns, andhealth care expenditures from patients,providers, or individuals in the generalpopulation.Health surveys typically collect information onrepresentative individuals in the targetpopulation, whether patients, physicians orgeneral population; surveys can thereforeprovide information about more members of

the target population, not just those who areparticipating in a given RCT, or members of aparticular health plan. As a result, health surveydata can make unique contributions aboutgeneralisability of treatments and their impacts,and about use of and expenditures for healthservices.The major limitation of health survey data forinitial coverage and reimbursement decisions isthe lack on relevant data on specific products.Survey data are also subject to issues ofsubjectivity and recall bias.[1]