stuart.mccully, Author at rwr-regs

Real World Evidence (RWE) 101 – Consent to Participate in Research vs Consent to Access and Process Sensitive Healthcare Data (GDPR)
Real World Evidence (RWE) 101 – Consent to Participate in Research vs Consent to Access and Process Sensitive Healthcare Data (GDPR)

2023, RWE 101

Real World Evidence (RWE) 101 – Consent to Participate in Research vs Consent to Access and Process Sensitive Healthcare Data (GDPR)

RWE 101 – Consent to Participate in Research vs Consent to Access and Process Sensitive Healthcare Data (GDPR)

Consent to participate in research and consent to access and process sensitive healthcare data are two different but overlapping types of consent, each governed by distinct legal and ethical principles. In the context of Real-World Evidence (RWE) studies:

[1] Consent to Participate in Research: This is the informed consent given by individuals to participate in a research study. Informed consent is a process by which researchers provide potential and enrolled participants with information about the study (purpose, procedures, risks, benefits, alternatives), and the participants voluntarily agree to participate. This consent can be withdrawn at any time, at which point the individual’s participation in the study would end.

[2] Consent to Access and Process Sensitive Healthcare Data: This relates to the consent given by individuals to have their personal and sensitive health data accessed and used for specific purposes, such as research. This type of consent is governed in Europe by the General Data Protection Regulation (GDPR). Under the GDPR, the use of health data is considered a processing of special category data and requires explicit consent, which must be freely given, specific, informed, and unambiguous.

In a RWE study, both types of consent may be (are) needed. The first ensures that participants agree to be part of the study and understand what will happen during the study. The second ensures that participants agree to their data being used in the manner specified, and it provides protections around how their data can be stored, transferred, and otherwise processed.

One key difference between these two types of consent is that withdrawal of consent to participate in the research study generally means the individual will not be part of the study going forward, but it does not necessarily mean that the data collected up to that point cannot be used. In contrast, under the GDPR, if an individual withdraws their consent to data processing, not only does the data processing have to stop, but in many cases, the data collected up to that point cannot be used further and may need to be deleted.

Another difference is that, while there are legal and ethical requirements to obtain informed consent for research participation in most cases, there are certain circumstances under which health data can be processed for research purposes under the GDPR without obtaining explicit consent, such as if the processing is necessary for reasons of public interest in the area of public health, or if the data has been anonymized.

In both cases, the principles of transparency, respect for persons, and their autonomy are paramount. Proper management of both types of consent is crucial for ethical research and for maintaining trust with study participants.

Real World Evidence (RWE) 101 – Consent to Participate in Research vs Consent to Access and Process Sensitive Healthcare Data (GDPR)stuart.mccully2023-08-07T17:41:42+00:00

Real World Evidence (RWE) 101 – Patient Retention
Real World Evidence (RWE) 101 – Patient Retention

2023, RWE 101

Real World Evidence (RWE) 101 – Patient Retention

RWE 101 – Patient Retention

Long-term Real-World Evidence (RWE) studies face significant challenges when it comes to patient retention, for several reasons:

[1] Time Commitment: Participants in RWE studies are often required to participate over extended periods, sometimes even years. This long-term commitment may lead to decreased interest and attrition over time, especially if the participants do not see immediate benefits from their participation.

[2] Life Changes: Given the long-term nature of RWE studies, life events such as changes in health status, relocation, changes in personal or financial circumstances, or simply a change in priorities can influence a participant’s ability or desire to continue in the study.

[3] Perceived Burden: Depending on the design of the study, the level of participant engagement required can vary widely. Some RWE studies may require frequent hospital visits, self-reporting of data, regular lab tests, or other potentially time-consuming activities. The perceived burden of these requirements can negatively impact retention.

[4] Lack of Engagement: If participants feel that they are just data points and do not feel personally engaged or valued, they may be more likely to drop out of the study. Personal engagement strategies, regular communication, and feedback are therefore crucial to keep participants motivated.

[5] Privacy and Data Security Concerns: In the era of digital health data, participants might worry about the potential misuse of their personal health information, which may lead to dropouts.

[6] Inadequate Understanding: If the participants do not fully understand the importance of their role, the relevance of the research, or the potential benefits to them or to society, they may be less likely to continue in the study. Education and clear communication are key to ensuring participants understand these aspects.

To address these challenges, researchers are increasingly looking to use technologies and strategies that can improve the participant experience and maintain engagement over time, such as remote monitoring technologies, digital health platforms, personalized engagement strategies, and clear, ongoing communication about the value and impact of the study.

Real World Evidence (RWE) 101 – Patient Retentionstuart.mccully2023-08-07T17:33:26+00:00

Real World Evidence (RWE) 101 – Patient Recruitment
Real World Evidence (RWE) 101 – Patient Recruitment

2023, RWE 101

Real World Evidence (RWE) 101 – Patient Recruitment

RWE 101 – Patient Recruitment

Real-world evidence (RWE) is health care information derived from real-world data (RWD). It can be generated through various study designs or analyses, including pragmatic clinical trials, observational studies, and health surveys. In the context of RWE, patient recruitment plays a significant role, as the data collected from these individuals helps in understanding the effectiveness, safety, and usage of medical products in the real world.

Traditional Patient Recruitment: In traditional methods, patient recruitment generally happens through methods like physician referrals, media advertising, patient registries, and patient advocacy groups. This method can be time-consuming, costly, and sometimes inefficient, as it often relies on manual efforts. It can also be challenging to find patients who fit specific inclusion and exclusion criteria for a particular study.

AI-Enabled Recruitment: Artificial intelligence (AI) has started transforming patient recruitment in many ways. AI can analyze vast amounts of real-world data from electronic health records (EHRs), medical claims, health surveys, and other digital health platforms to identify eligible patients rapidly. This approach reduces the recruitment timeline and the costs associated with patient enrollment.

AI algorithms can predict the likelihood of patients participating in the study, improving the precision of recruitment. They can also monitor and analyze patient behavior, enabling the refinement of recruitment strategies in real-time. AI can further enhance the diversity of recruited patients by considering a wide range of demographic and geographic factors, leading to a more inclusive and representative study.

AI-enabled recruitment can also help in mitigating potential biases in patient selection by utilizing a data-driven approach. By analyzing historical clinical trial data, AI models can identify patterns and biases in previous studies and correct them in future ones. Furthermore, AI can help in patient retention by predicting the potential drop-out risks and enabling timely intervention.

In conclusion, while traditional methods are essential and remain relevant in certain contexts, AI-enabled recruitment offers the possibility of increased speed, reduced costs, and improved diversity and representativeness of patients in studies generating real-world evidence.

Real World Evidence (RWE) 101 – Patient Recruitmentstuart.mccully2023-08-07T17:26:18+00:00

Real World Evidence (RWE) 101 – HARPER
Real World Evidence (RWE) 101 – HARPER

2023, RWE 101

Real World Evidence (RWE) 101 – HARPER

RWE 101 – HARPER

Regulatory agencies, health technology assessors, and payers are increasingly interested in studies that make use of real-world data to inform regulatory and other policy or clinical decision-making. However, concerns over the credibility of real-world evidence studies have led to calls for more transparency on the design and conduct of RWE studies.

A joint task force between ISPE and ISPOR created a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The HARPER template provides clarity, structure, and a common denominator regarding the level of operational detail, context, and rationale necessary in a protocol.

HARPER = HARmonized Protocol Template to Enhance Reproducibility of hypothesis evaluating real-world evidence studies on treatment effects

Link: https://lnkd.in/erkyU2iT

Four protocol templates were identified for RWE studies:

1. The European Medicines Agency’s (EMA) Guideline on Good Pharmacovigilance Practices (GVP) Module VIII – post-authorizations safety studies (PASS) template,
2. ISPE’s guidelines for good pharmacoepidemiology practice (ISPE GPP) section on protocol development,
3. The National Evaluation System for health Technology (NEST) protocol guidance, and
4. The Structured Template and Reporting Tool for Real World Evidence (STaRT-RWE).

The HARPER protocol contains nine sections, including a title page, abstract, and a table for amendments and updates. Each section includes structured free text, a structured table, or a figure, and a free-text section to lay out context and rationale for scientific choices.

The study design diagram shows the context and rationale for the study setting, time 0 (index date), inclusion criteria, exclusion criteria, variables, exposure, outcome, follow up, covariates, sensitivity analyses, data sources, metadata, and software used in the study.

The data sources section includes a free text component followed by a structured table for specifying data sources. The data sources section can also include a detailed evaluation of the fitness-for-purpose of data source options.

Overall, the HARPER framework is a valuable resource for researchers and clinicians who are planning or conducting RWE studies. The framework can help to ensure that protocols are well-designed and will produce high-quality evidence.

Real World Evidence (RWE) 101 – HARPERstuart.mccully2023-08-07T17:19:12+00:00

Real World Evidence (RWE) 101 – STaRT-RWE
Real World Evidence (RWE) 101 – STaRT-RWE

2023, RWE 101

Real World Evidence (RWE) 101 – STaRT-RWE

RWE 101 – STaRT-RWE

START-RWE (Structured Template for Planning and Reporting on the Implementation of Real World Evidence Studies) was developed to address the need for improved transparency and reproducibility in real-world evidence (RWE) studies.

Link: https://lnkd.in/dGp3auQ

The template includes sections on study design, data collection, data analysis, and reporting. The study design section includes questions about the study’s objectives, population, intervention, comparator, outcomes, and study period. The data collection section includes questions about the data sources, data collection methods, and data quality assurance procedures. The data analysis section includes questions about the statistical methods that will be used to analyze the data. The reporting section includes questions about the study’s findings, limitations, and implications.

The template is intended to be used by researchers and clinicians to develop and implement RWE studies in a rigorous and transparent manner. The template can also be used by funders, regulators, and other stakeholders to assess the quality of RWE studies. The publication includes a number of case studies that illustrate how the STaRT-RWE template has been used to develop and implement RWE studies.

In the context of RWE transparency and reproducibility, START-RWE is important for the following reasons:

1. Transparency: The comprehensive reporting facilitated by START-RWE allows for complete transparency in the methods and findings of RWE studies. It ensures that all important details regarding the study design, data sources, analysis methods, results, and interpretations are fully disclosed and clearly communicated. This openness supports better interpretation and use of study findings.
2. Reproducibility: Transparency leads to reproducibility. By providing a comprehensive and detailed account of the study methods, START-RWE enables other researchers to replicate the study, which is a cornerstone of scientific validation. Reproducibility also allows for the results of RWE studies to be confirmed and refined in different populations and settings, enhancing their generalizability and impact.

The STaRT-RWE template is a valuable resource for researchers and clinicians who are planning or conducting RWE studies. The template can help to ensure that RWE studies are conducted in a rigorous and transparent manner, which can improve the quality of the evidence and ultimately lead to better healthcare decision-making.

Real World Evidence (RWE) 101 – STaRT-RWEstuart.mccully2023-08-07T17:12:23+00:00

Real World Evidence (RWE) 101 – Protocol Design and ISPE GPP
Real World Evidence (RWE) 101 – Protocol Design and ISPE GPP

2023, RWE 101

Real World Evidence (RWE) 101 – Protocol Design and ISPE GPP

RWE 101 – Protocol Design and ISPE GPP

The International Society for Pharmacoepidemiology (ISPE) Guidelines for Good Pharmacoepidemiology Practices (GPP) are a set of best practices for the conduct of pharmacoepidemiologic research, which includes the creation and analysis of real-world evidence (RWE).

Link: https://lnkd.in/eHSZVunX

ISPE GPP provides a benchmark for quality in pharmacoepidemiology studies, covering all aspects of the research process from study design and conduct to communication of study results. They provide guidance on maintaining ethical standards, ensuring data quality and integrity, managing study data and documents, managing and reporting adverse events, and many other facets of study conduct. Regulatory bodies in the USA, Canada, EU and Germany recommend that ISPE should be considered by marketing authorisation holders and investigators for the development of study protocols, the conduct of studies and the writing of study reports.

In the context of RWE and RWE study protocols, ISPE GPP is particularly important for the following reasons:

1. Enhanced Credibility and Quality of Studies: Adhering to ISPE GPP can help to ensure that RWE studies are designed and conducted to a high standard, which enhances their credibility and the reliability of their results.

2. Consistency and Comparability: ISPE GPP provide a consistent framework for RWE studies, which can facilitate comparison between studies and encourage uniformity in research practices. For example:
– Section II of ISPE GPP provides detailed guidance on protocol design and context
– Section IV covers study conduct and study reporting

3. Ethical Conduct: The guidelines provide recommendations for maintaining ethical standards throughout the research process, including the protection of study participants and the use of their data.

4. Regulatory Compliance: RWE is being increasingly used by regulatory agencies to inform decisions about the safety and effectiveness of treatments. Adhering to ISPE GPP can help to ensure that studies meet the standards expected by these agencies.

5. Transparency: The guidelines promote transparency in the reporting of study methods and results, which is crucial for the interpretation and validation of RWE.

6. Archiving: In the absence of national requirements or guidance, ISPE GPP recommends that study-related materials be maintained for at least five years after final report or first publication of study results.

In essence, following ISPE GPP can ensure that RWE studies are conducted to a high scientific and ethical standard, increasing their value to healthcare providers, regulators, and patients.

Real World Evidence (RWE) 101 – Protocol Design and ISPE GPPstuart.mccully2023-08-07T17:03:05+00:00

Real World Evidence (RWE) 101 – Protocol Design and Scientific Best Practices
Real World Evidence (RWE) 101 – Protocol Design and Scientific Best Practices

2023, RWE 101

Real World Evidence (RWE) 101 – Protocol Design and Scientific Best Practices

RWE 101 – Protocol Design and Scientific Best Practices

Designing a robust Real-World Evidence (RWE) study is crucial for generating reliable and valid insights that are acceptable to regulators. Here are some scientific best practices to consider according to regional drug regulatory authorities:

EUROPEAN UNION – According to the European Medicines Agency (EMA), relevant scientific guidance should be considered by marketing authorisation holders and investigators for the development of study protocols, the conduct of studies and the writing of study reports…These scientific guidelines include the:
1. ENCePP Guide on Methodological Standards in Pharmacoepidemiology
2. ENCePP Checklist for Study Protocols, and
3. Guidelines for Good Pharmacoepidemiology Practices of the International Society of Pharmacoepidemiology (ISPE GPP)
Ref: Section VIII.B.1. of GVP Module VIII

GERMANY – The observation plan is to be drawn up according to recognized recommendations of scientific or regulatory guidelines…for example:
1. Guidelines for Good Pharmacoepidemiology Practices of the International Society for Pharmacoepidemiology (ISPE GPP),
2. Recommendations of the ” ENCePP Guide on Methodological Standards in Pharmacoepidemiology”, and
3. Guidelines for Good Epidemiological Practice (GEP) of the German Society for
Epidemiology (DGEpi)
Ref: Section 2.7.1 of the BfArM/PEI Recommendations – December 2022

CANADA – All research protocols should be well-designed and include a comprehensive assessment of good research principles. There are fifteen key elements that should be considered for each protocol, and are reflective of the:
1. European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) Protocol Checklist, and
2. The Guidelines for Good Pharmacoepidemiology Practices (GPP).
Both prospective and retrospective designs should attempt to address each element, or provide justification why it may not be applicable to the specific study.
Ref: Health Canada – Elements of Real World Data/Evidence Quality throughout the Prescription Drug Product Life Cycle, March 2019

USA – According to the FDA’s “Best Practices for Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data” of May 2013, the following provide general guidance applicable to all pharmacoepidemiologic safety studies:
1. ISPE guidelines (ISPE GPP),
2. STROBE reporting framework, and
3. The ENCePP methods checklist
Ref: FDA Guidance – Best Practices for Conducting and Reporting Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data

These scientific best practices will help ensure that the RWE study is robust, credible, and provides meaningful information to patients, healthcare providers, and policy makers.

Real World Evidence (RWE) 101 – Protocol Design and Scientific Best Practicesstuart.mccully2023-08-07T16:51:55+00:00

Real World Evidence (RWE) 101 – Study Designs
Real World Evidence (RWE) 101 – Study Designs

2023, RWE 101

Real World Evidence (RWE) 101 – Study Designs

RWE 101 – Study Designs

Real-world evidence (RWE) studies are becoming increasingly important in healthcare decision-making. There are various study designs used to generate RWE, each with their unique benefits:

[1] Cohort Studies: Cohort studies are observational in nature, where two or more groups (cohorts) distinguished by their exposure to a certain factor (like a medical treatment or lifestyle choice) are followed and assessed to determine the effect of that exposure. These studies are advantageous in studying rare outcomes, multiple outcomes, or outcomes that take a long time to develop.

[2] Case-Control Studies: These studies start with the outcome and then look backward to find the exposure. They’re efficient for studying rare diseases or diseases with a long latency period, as well as multiple exposures. However, they may not be as reliable as cohort studies due to potential recall bias.

[3] Cross-Sectional Studies (Prevalence Studies): These studies observe a defined population at a single point in time or time interval. They’re useful in understanding the burden of a disease in a population, assessing public health needs, and planning healthcare services.

[4] Registry-Based Studies: These are observational studies where data are collected prospectively or retrospectively for patients with a particular condition or who are undergoing a specific procedure. Registry-based studies provide long-term, real-life data about prognosis, adverse events, quality of life, and cost-effectiveness.

[5] Pragmatic Clinical Trials (PCTs): Unlike traditional randomized clinical trials, PCTs are designed to determine the effectiveness of interventions in real-world routine practice conditions. They often include a more diverse patient population, multiple care settings, and less rigid protocols.

[6] Retrospective Studies: This involves analyzing existing datasets (like EHRs or insurance claims databases) to find associations or trends. This is also known as secondary use of existing data. While these are generally quicker and less expensive, they are subject to the limitations of the existing data, which may not have been collected for research purposes.

[7] Prospective Observational Studies: In these studies, subjects are followed over time with data collected about various factors that might influence the outcome of interest. These studies are useful in understanding the natural history of disease and the effectiveness of different treatments in the real world. These studies usually include both secondary data (data collected for a different purpose) and primary data (data collected specifically for the purposes of the study).

Real World Evidence (RWE) 101 – Study Designsstuart.mccully2023-08-07T16:44:52+00:00

Real World Evidence (RWE) 101 – Protocol Considerations
Real World Evidence (RWE) 101 – Protocol Considerations

2023, RWE 101

Real World Evidence (RWE) 101 – Protocol Considerations

RWE 101 – Protocol Considerations

Real-world evidence (RWE) study protocols and clinical trial protocols both outline the design and conduct of a study. However, they are distinctly different in several ways given the differences in objectives, methodologies, settings, and populations involved in clinical trials versus RWE studies.

[1] Objectives: The main objective of a clinical trial is to evaluate the efficacy and safety of a medical intervention in a controlled environment, usually by comparing it to a placebo or standard treatment. On the other hand, RWE studies typically aim to understand how an intervention works in routine clinical practice, often focusing on outcomes such as long-term effectiveness, side-effects, quality of life, and cost-effectiveness.

[2] Study Design and Methodology: Clinical trials, especially phase III, are predominantly randomized controlled trials (RCTs) where subjects are randomly assigned to the intervention or control group to minimize bias. They follow a pre-specified protocol and are conducted under tightly controlled conditions. RWE studies, on the other hand, are typically observational in nature and analyze data from sources like electronic health records (EHRs), claims databases, or patient registries.

[3] Setting: Clinical trials are conducted in specific, controlled environments and follow a strict protocol. RWE studies are conducted in routine clinical practice settings, making them more representative of ‘real-world’ conditions.

[4] Population: Clinical trials often have strict inclusion and exclusion criteria, resulting in a relatively homogeneous group of participants. This can limit the generalizability of the results. RWE studies, in contrast, involve broader, more diverse populations (including those often excluded from trials like the elderly, people with multiple co-morbidities, etc.), making the findings more generalizable to everyday practice.

[5] Data Collection: In clinical trials, data collection is rigorous, detailed, and specific to the trial endpoints. Adverse events are actively sought and documented. RWE studies primarily rely on existing data sources such as EHRs, patient registries, or insurance claims data. This can potentially lead to incomplete or inaccurate data.

[6] Intervention: In clinical trials, the intervention (dosage, frequency, duration, etc.) is pre-specified and strictly monitored. In RWE studies, interventions reflect routine clinical practice and may vary widely.

[7] Follow-up: Clinical trials have a defined follow-up period while RWE studies can often provide information on long-term outcomes, given they use data from routine clinical practice over longer periods.

While clinical trials provide the highest level of evidence for determining a treatment’s efficacy, RWE studies complement this by providing evidence on real-world effectiveness and long-term safety.

Real World Evidence (RWE) 101 – Protocol Considerationsstuart.mccully2023-08-07T16:38:31+00:00

Real World Evidence (RWE) 101 – PASS Approval Requirements
Real World Evidence (RWE) 101 – PASS Approval Requirements

2023, RWE 101

Real World Evidence (RWE) 101 – PASS Approval Requirements

RWE 101 – PASS Approval Requirements

Post-authorisation safety studies (PASS) are studies conducted after a medicine has been authorized (licensed) with the goal of acquiring more data about the medicine’s safety, or to measure the effectiveness of risk-management measures. These studies play a vital role in understanding the safety and effectiveness of a drug in a real-world context.

While specific requirements can vary by country, they often include:

[1] Ethics Committee Approval: Any study involving human subjects generally needs to be approved by an Ethics Committee (EC) or Institutional Review Board (IRB). This body ensures that the study is designed and implemented in a manner that respects the rights, safety, and well-being of the participants (i.e., compliance with the Declaration of Helsinki).

[2] Regulatory Approval: Depending on the country and type of PASS (e.g., Category 1, 2, 3, or voluntary PASS) additional regulatory approval may be needed. For instance, in the European Union, any category 1 or 2 PASS protocol of a medicine authorised through the Centralised Procedure has to be approved by the European Medicines Agency (EMA).

[3] Data Protection Laws Compliance: Studies must comply with all relevant data protection laws (e.g., GDPR). This includes regulations on the use and sharing of personal data, as well as provisions for protecting the privacy of participants.

[4] Study Registration: Most categories of PASS must be registered in a public database (i.e., EU PAS Register). This increases transparency and allows for the tracking and sharing of results.

[5] Adherence to Good Pharmacovigilance Practices (GVP): This is especially pertinent in the EU, where PASS must adhere to Module VIII of the GVP.

[6] Provision of Adequate Information to Participants: There’s usually a requirement that all participants must be given adequate information about the study, and that informed consent must be obtained.

[7] Reporting Requirements: There will be requirements to report adverse events, progress, and the final results to the respective regulatory bodies (i.e., ethics committees and national competent authorities).

However, these requirements can be subject to change over time and may vary in specifics from one country to another. Therefore, it’s crucial to consult with the appropriate regulatory body or a regulatory affairs professional familiar with these regulations when planning a post-authorisation safety study.

Real World Evidence (RWE) 101 – PASS Approval Requirementsstuart.mccully2023-08-07T16:30:41+00:00

About stuart.mccully

Real World Evidence (RWE) 101 – Consent to Participate in Research vs Consent to Access and Process Sensitive Healthcare Data (GDPR)