Is RWD needed for post-listing control of PE exempt drugs?

for drugs listed through the pharmacoeconomic evaluation exemption pathway

The lack of robustness in data criticized…has clear limitations over RCT

Can manage high-priced drugs with existing RSA pathways such as Performance-based type and Expenditure Cap type RSA

The budget is tight, but the use of high-priced drugs continues to rise.

 

The government is beginning to feel the strain of the systems it has put in place to increase access to new drugs, especially the pharmacoeconomic evaluation (PE) exemption system, which is increasingly being utilized and being subject to criticism.

 

"The purpose of the post-listing control system is to secure additional evidence for medicines that have unclear safety and efficacy for patients.

 

It will improve the quality of Korea’s healthcare by providing a medical reaffirmation process for such medicines." This was the government's stated intent.

 

The government's good intentions aside, the industry has not received it well.

 

This is due to the fear that the introduction of the system will eventually lead to "drug price cuts".

 

Add to that the idea of using real-world evidence (RWE), or real-world data (RWD), to reevaluate drugs reimbursed through the PE exemption track, the concept has raised industry eyebrows.

 

RWE lacks evidence base...encourages “Korea passing” The approval of a new drug is usually based on a randomized controlled trial (RCT).

 

The PE evaluation and cost-effectiveness of the new drugs are also conducted based on this data.

 

However, unlike RCTs, RWDs are not controlled data that are designed to accurately determine the efficacy of a drug.

 

There are many variables that can introduce bias, such as what comorbidities the patient has, what prior medications they have taken, and whether the patient was adherent to the dose and frequency of the medication.

 

The generally accepted levels of data evidence from high to low are meta-analyses, systematic reviews, RCTs, controlled clinical and observational studies, uncontrolled observational studies, case reports, and expert opinion; RWE is considered to be at the "uncontrolled observational study-case report" level.

 

The Korean Research-based Pharmaceutical Industry Association (KRPIA) said, "RWE can be used to extract any desired results, depending on the intent of the collating entity.

 

It is a risky idea to use data with a high risk of bias for the post-listing control of listed drugs.

 

Since it is not generated in a controlled environment like an RCT, there are too many other factors to consider, including numerous crossovers, comorbidities, and use of concomitant medications." "RWEs can create contradictions and can overturn the results of RCTs that are higher level evidence.

 

Rather, RWE should be used as a complementary tool to address uncertainties at the approval stage." Some argue that the introduction of such a post-listing control system could aggravate the "Korea passing" phenomenon in the pharmaceutical industry.

 

If the government requires companies to submit data such as RWE post-listing, the companies will have to spend additional costs and time to generate such data, and if the data is then used as a basis for drug price cuts, it is inevitable that more pharmaceutical companies will be skeptical about launching new drugs in Korea.

 

"Creating customized RWE data for each individual country is a huge burden for pharmaceutical companies," said a Market Access (MA) representative from a multinational pharmaceutical company.

 

Even if a post-listing control system is introduced, the necessary data should be generated by a state-led registry, and the quality be assured."

Must it be RWD?

 

Can’t the drugs be managed with existing systems? Whether RWD is necessary is quite controversial.

 

Korea's post-listing control system is already criticized by the industry for being tight.

 

The Ministry of Health and Welfare proposed a plan to strengthen reimbursement management for high-priced drugs for serious diseases in 2023.

 

In the plan, "high-priced drugs" were defined as ▲"one-shot drugs" that are expected to have long-term effects with a single treatment or drugs that require more than KRW 300 million/year of national health insurance finances per person, and were subject to reimbursement management measures.

 

As a result, currently listed innovative drugs that have uncertainties (e.g., Kymriah, Zolgensma, Luxturna) are managed through the “performance-based reimbursement” type of the Risk-Sharing Agreement (RSA) scheme as well as the cost-effectiveness-based post-marketing evaluations, etc.

 

The industry’s point is that systems already in place today are sufficient to manage the uncertainty that accompanies the effect of new drugs.

 

"High-priced drugs have been reimbursed through various types of RSA, including performance-based and expenditure cap type RSA, so it is questionable whether additional follow-up measures are really necessary in addition to these arrangements, especially when the pharmaceutical companies already filter out patients that show uncertain efficacy and safety with their drugs and refund the expenses to the government under performance-based RSA," said KRPIA.

 

"For ultra-high-priced drugs that cost over KRW 300 million per person a year and have a small number of target patients, they should be managed through a patient-level performance-based RSA or an individual contract-based drug performance evaluation system that generates individual data for each drug's situation," it added.