Global post-marketing study (PMS)

A global post-marketing study (PMS) is required to assess the long-term safety and efficacy of treatments across therapeutic areas. Two of the most prevalent and interrelated chronic diseases worldwide include type 2 diabetes mellitus (T2DM) and hypertension. When combined, type 2 diabetes and hypertension significantly increase cardiovascular morbidity and death, requiring ongoing pharmaceutical treatment and several medication regimens.

Now, here’s the catch: scientific trials tell us how pharmaceuticals function in controlled circumstances, but they don’t always show us what happens when actual people, with various ailments, varying lives, and different genetics, start using them every day. PMS is useful in this regard. They serve as a link between carefully designed trials and inept real-world execution.

This article offers a thorough overview of post-marketing studies in T2DM and hypertension, including the disease epidemiology, the goals and significance of PMS, study designs, legal requirements, global challenges, the role of high-quality data and emerging technologies, and market and commercial outcomes.

Epidemiological trends and disease burden of T2DM and hypertension

Type 2 diabetes mellitus (T2DM) is a lifelong condition where the body struggles to use insulin properly, causing a rise in blood sugar levels. It affects daily life, overall well-being, and creates a significant strain on healthcare finances.

Hypertension, more commonly known as high blood pressure, is defined as a reading of 140/90 mmHg or above. It may seem common, but if left unchecked, it can silently damage the heart, brain, and kidneys, making it far more dangerous than it first appears.

T2DM and hypertension are more than statistics; they affect millions of people whose quality of life is impacted every day. The following statistics seem self-evident:

Diabetes affects over 10% of people worldwide, and its prevalence is projected to rise rapidly over the next 20 years. Every year, it already results in more than a million deaths.
Almost half of the 1.28 billion adults who suffer from hypertension are unaware that they have it. Most of the population resides in low- and middle-income nations, and has the lowest rates of diagnosis and treatment.

Geographical distribution of hypertension and type 2 diabetes worldwide

Type 2 diabetes mellitus (T2DM) and hypertension are common across the globe; however, they are not prevalent in all regions equally. Low- and middle-income countries such as Central Asia, South Asia, and Southern Sub-Saharan Africa report the highest incidence rates. In fact, T2DM is rising fastest in lower socio-demographic regions, especially in countries like China and India.

Hypertension follows a similar pattern. According to the WHO, over 75% of people living with high blood pressure are in low- and middle-income nations. Prevalence of hypertension in the Americas is at around 18%, while it is found to be highest in Africa (27%).

Together, these trends indicate a high caseload worldwide, underlining the urgent need for regionally specific strategies for managing these intertwined chronic diseases.

Why is a global post-marketing study (PMS) essential?

While clinical trial phases (phase I-III) evaluate safety and efficacy in strictly controlled conditions, they cannot entirely reflect the diversity of patient experiences. PMS fills this gap by systematically monitoring the acceptability, safety, and efficacy of medicines in actual populations. They allow us to:

Evaluate long-term safety: Identify side effects that emerge later (e.g., antihypertensive drug safety: electrolyte imbalance, SGLT2 inhibitor-associated infections).
Evaluate practical efficacy: Check whether effects such as blood pressure decrease or control of blood glucose result in actual advantages.
Assess cardiovascular and renal risk: Assess the impact of therapies on the prevention or attenuation of the development of CVD and CKD, the primary complications of coexisting T2DM and hypertension.
Recognize pharmacological interactions: Pharmacological interactions are important to recognize because patients take more than one drug at a time to manage comorbid conditions.
Monitor special groups of populations: Track a group of populations, like the elderly and pregnant. Recognize patients with chronic kidney disease.
Informs regulatory and clinical choices: Post-approval evidence affects guidelines and formulary status, as well as regulatory and clinical considerations.

How are these studies done: Types of PMS in T2DM and hypertension

Continuous monitoring assesses the safety, effectiveness, and real-world impact of T2DM and hypertension drugs after approval. Common approaches include:

Spontaneous Reporting Systems (SRS):
- Unusual or unforeseen adverse drug reactions (ADRs) are measured by spontaneous reporting systems (SRS).
- Example: Severe hypoglycemia reports with sulfonylureas.
Prescription Event Monitoring (PEM):
- PEM monitors patient outcomes after a drug has been licensed.
- Monitors ADRs and compliance in patients with diabetes and hypertension.
Patient registries:
- Gathers longitudinal information on a particular drug class or disease.
- Example: Diabetes registries to monitor cardiovascular outcomes.
Case-control studies:
- Identifies correlations between drug exposure and severe dangers (e.g., some antihypertensives and angioedema).
Randomized phase IV trials:
- Compare the relative effectiveness of new vs. conventional treatments.
- Example: SGLT2 inhibitors and DPP-4 inhibitors in real-world settings.

Together, these post-marketing study approaches help bridge the gap between controlled clinical trials and the realities of everyday medical practice.

Regulatory requirements for PMS in T2DM and hypertension

Regulators mandate post-marketing studies. Worldwide, agencies implement robust frameworks to ensure continuous monitoring of T2DM and hypertension drugs for safety and efficacy after approval.
Key regulatory requirements include:

U.S. FDA
- The US FDA requires Risk Evaluation and Mitigation Strategies (REMS) for high-risk drugs.
- New antidiabetic drugs must pass through cardiovascular outcomes trials (CVOTs).
European Medicines Agency (EMA)
- The European Medicines Agency (EMA) requires Risk Management Plans (RMPs) and Periodic Safety Update Reports (PSURs).
- Monitors fixed-dose combinations and new antihypertensives.
India & Asia-Pacific regulators:
- Increasingly mandate PMS in high-prevalence diseases like T2DM and hypertension.
- Researchers must obtain local registry data before broad approval.
Frameworks for WHO/ICH:
- Promote the standardization of post-marketing and pharmacovigilance regulation globally.

Challenges in a global post-marketing study for T2DM and hypertension

There are several obstacles to the successful implementation of PMS across various geographies and demographics:

Regulatory fragmentation: Reporting requirements vary by nation.
Disease prevalence variability: Genetics, environment, or comorbidities may cause ADRs to vary by region.
Underreporting of ADRs: ADR underreporting is particularly problematic in LMICs due to their weaker health systems.
Polypharmacy: ADR attribution is challenged by the fact that many patients take several medications.
Data integration issues: Registry data from different health systems is hard to standardize.
Limited doctor participation: Physicians may fail to report adverse drug effects regularly.

Technology for PMS in T2DM and hypertension

PMS is increasingly using digital tools and advanced analytics that improve monitoring and reporting to get past these obstacles:

Electronic Health Records (EHRs): Real-world tracking of glucose, blood pressure, and ADRs.
Big data & Artificial Intelligence (AI): Predicts safety signals (e.g., risk of heart failure with specific antidiabetics).
Wearables and digital health tools: such as smart blood pressure monitors and continuous glucose monitors, provide real-time pharmacovigilance data.
Blockchain for pharmacovigilance: Offers secure, transparent global data exchange.
Mobile apps: Instruct patients to report adverse drug reactions (ADRs) themselves, since this is especially useful in the management of chronic diseases.

These advancements enable researchers, clinicians, and regulators to combine global datasets, detect safety issues early, and involve patients actively in the pharmacovigilance process.

Market and commercial implications of PMS in T2DM and hypertension

In addition to patient safety, PMS data is strategically significant for payers, pharmaceutical companies, and healthcare providers. This is how:

Increases trust between patients and doctors: Shows long-term tolerability and safety.
Influences on prescribing behavior: Medications with established cardiovascular safety are more widely used.
Guides payer and insurance decisions: PMS information is essential for approving reimbursements.
Expands therapeutic indications: Additional benefits include SGLT2 inhibitors for heart failure in non-diabetics.
Mitigates commercial risks: Early detection of safety issues helps avoid widespread withdrawals.

PMS has a wider function as a preventative public health tool that safeguards populations. It does so by guaranteeing therapies are safe and effective in the real world.

Conclusion

Post-marketing studies, or PMS, are now a must for trial operations in order to ensure that therapies actually provide long-term advantages in real-world situations. In contrast to pre-approval trials that concentrate on controlled conditions, PMS provides insight into what actually occurs after medications are in patients’ possession, including their long-term safety, adherence, the effects of multiple medications (polypharmacy), and how results differ among populations and geographical areas.

The success of PMS for sponsors and regulators depends on three main pillars: powerful systems that can integrate data internationally, clear and uniform regulatory frameworks, and active participation from all stakeholders, including patients, clinicians, and others.

Are you facing challenges in designing or executing a global post-marketing study (PMS) to evaluate the long-term safety and effectiveness of your therapies?

Our team of experts can help you overcome country-specific regulatory barriers, streamline patient recruitment, and leverage digital tools to generate valuable real-world evidence. Get in touch with us to share your challenges and discuss them with our expert team.