EvidenceSystematic ReviewPharmaHTA

Multi-partner teams are critical in the journey of a new drug from bench to bedside

Multi-partner teams are critical in the journey of a new drug from bench to bedside cover

In the field of systematic reviews and evidence synthesis, strong, multi-partner teams are critical for moving new drugs from early development and testing in the lab to treating people in the clinic.

Patients, healthcare providers, government agencies, systematic review companies and pharmaceutical organisations all represent key partners that form these important, impactful infrastructures.

Pharmaceutical companies incubate the ideas – and bring the budgets

Pharmaceutical companies provide big budgets to spark and nurture new ideas in the lab that can be developed to provide new ways to treat patients experiencing diseases with important unmet needs. At later points in the drug development pipeline, the most promising drugs or treatment approaches are further supported by pharmaceutical companies when they initiate large, multi-million pound, often multinational clinical trials. These trials represent a crucial part of transitioning new therapies from the lab to the clinic, and provide critical information on how safe and effective a new therapy may be.

Patients drive the data

Patients, often through the recommendation of their healthcare providers, form a key partner with pharmaceutical companies when they agree to participate in clinical trials. Often, they are not paid for their participation, and have to place not only their trust, but their very lives, in the idea that a new drug may provide them with a similar or improved therapeutic experience than the current best standard-of-care, i.e. their existing treatment option(s).

The evidence that these patients ultimately generate throughout the course of their participation in a clinical trial not only has the potential to provide a benefit for them as an individual, but also has the potential to help future patients who will come after them. Without patient buy-in, clinical trials can flounder and be terminated early due to poor recruitment.

Healthy volunteers also represent an incredibly important trial partner, as they often participate in the earliest stage clinical trials and often assume more risk than a patient volunteer as they are involved in determining the dose at which a new drug may develop unwanted side effects.

Patients can also contribute valuable guidance on the design of a clinical trial before it begins, providing input on which health outcomes are most important to them. Often, it becomes clear that what a researcher considers to be the most important clinical or safety outcome on paper (for example, how often a patient experiences a stroke as a side effect) may not be what a patient feels is most important to them (for example, they may prioritise their overall quality of life rather than the occurrence of a specific event, like a stroke).

Putting the evidence together

Once a clinical trial has ended, systematic review (SR) companies partner with big Pharma to take a deep dive into the evidence and compare the data from a company’s new drug with other drugs that are used for the same disease. These are usually drugs that are either recommended as the current standard-of-care, currently on the market for that disease or are getting close to being approved.

At Mtech Access, we follow guidelines from the Cochrane Collaboration, Canadian Agency for Drugs and Technologies in Health (CADTH), the Centre for Reviews and Dissemination, PRISMA and PRESS, among others, to create the highest quality systematic reviews for submission to Health Technology Assessment (HTA) agencies.

We start by running in-depth searches across multiple formal databases and additional grey literature sources, like conferences, to identify the broadest range of available evidence. We then screen the records we find to identify the evidence that is relevant to our research question. We extract all the data from the records we find, and put this together either in a qualitative report or a quantitative report (such as a meta-analysis or network meta-analysis). This ultimately allows us to identify where the overall balance of evidence falls, form conclusions based on these trends, and identify important evidence gaps where further research is needed.

We also problem-solve for Pharma so as to deliver the best available evidence to illustrate their work in a transparent, reproducible way. The same approach can be taken for the patient journey, providing qualitative evidence to highlight patient experiences with a particular drug. This is often based on real-world evidence, which can provide a wider snapshot of the evidence pool, although important biases and limitations must be acknowledged.

Assessing the evidence

HTA agencies, such as the National Institute for Health and Care Excellence (NICE) in the UK or the Federal Drug Administration (FDA) in the USA, represent the last stop in the partnership that provides access to promising new drugs for patients who need them.

These agencies act as gatekeepers who make sure that any newly approved drugs provide both a clinical benefit and a purchase price that either matches or improves on existing drugs for the same disease – known as the cost-effectiveness threshold.

For each new drug submission, HTA agencies typically employ an evidence review group to provide a critical appraisal of the data submitted by a pharmaceutical company. These assessments form part of a series of formal committee meetings, often made up of researchers, NICE staff, patients, special interest groups and others, where decisions are made about future patient care.

Ultimately, the appraisal of new drugs or treatment approaches by HTA agencies can be a lengthy process, with several rounds of conversations between multiple partners. These are often centred around any uncertainty in the evidence, pricing agreements, access arrangements and the plan for long-term monitoring of safety and efficacy in the real world if a drug does receive approval.

Partnerships for purpose

Overall, patients, healthcare providers, government agencies, systematic review companies and pharmaceutical organisations all form a key partnership that enables the most promising new drugs to transition from bench to bedside. Strengthening these partnerships, enhancing collaboration and accelerating innovation remain critically important ongoing goals to deliver the most cutting-edge new therapies to the patients who need them.