Regulators are considering introducing the post-de-factor management system of drugs, in which they reevaluate the efficacy of reimbursed drugs by using Real World Data and weed out those that do meet certain standards.

Korea Cancer Study Group (KCCG) proposed so at a public hearing under the title of “Ways to evaluate and manage medicines after registration on reimbursement list,” held at the Korea Press Center in downtown Seoul, on Wednesday. The group jointly organized the event with the Korea Health Insurance Service (KHIS).

To work out a reasonable follow-up management method of drugs already registered for reimbursement, by using clinical data, KHIS asked the group to conduct the research. And they released primary results of the study at the public hearing.

Proposal for reevaluation based on Real World Data
After registering drugs for reimbursement, the basis of evaluation is Real World Data, which are patients’ health information data, such as electronic health records and insurance claims, regularly sent from various sources. Officials analyze Real World Data and use Real World Evidence – results of using medicines and clinical basis for potential advantages and risks – for evaluating them.

France, Sweden and Netherlands have already introduced the post-de-facto management system of reimbursed drugs, using Real World Evidence.

Taiwan in particular revised related regulations in September to mandate the reevaluation of reimbursed drugs within five years of registration, by using Real World Evidence. If the medications’ duration of life is lower than the results of clinical trials, the regulators obliged drugmakers to refund part of the reimbursement. Also subject to the mandatory reevaluation are the drugs which record reimbursement payment worth 500 million New Taiwan Dollars or more even in one of those five years.

Professor Ahn Jeong-hun of the Fusion Healthcare Department at Ewha Womans University, who took part in the research, proposed that KHIS conducts “prospective model” research concerning medicines to be registered for reimbursement after 2020, by making contracts with pharmaceutical companies.

In making contracts about follow-up management, KHIS should specify study design, standards for excluding from selection, indications, collectible variables, management indexes and win the agreement of pharmaceuticals, Professor Ahn said. To enhance transparency, it should de-identify collected information to protect individuals’ privacy, and make it public for use by everyone, including the drugmakers, he pointed out.

Also, Ahn said, KHIS will be able to carry out a “retrospective model” study on drugs to be registered after 2020 but have little needs for additional clinical tests, adding that the retrospective model study can be applied to Rish Sharing Agreement and the renewal of contracts.

Another researcher suggested the KHIS sets up a tentatively titled “Committee for post-de-facto management of drugs” and allows it to play the role of selecting and management medicines subject for follow-up management and provide advice for examination. The proposed committee will be composed of two or three officials each from KHIS, and the Ministry of Health and Welfare, three or four clinical experts, one or two members from the patient and civic groups, one or two statistical experts and one or two specialists analyzing the economic feasibility, he suggested.

Professor Lee Dae-ho of the Medical Oncology Department at Asan Medical Center in Seoul enumerated the types of drugs to be subject for follow-up management, such as medicines with relatively uncertain clinical efficacy, those with relatively uncertain cost-benefit effects (economic feasibility), those with relative bigger fiscal impacts, and those with high degrees of suspicious disease.

“No drugs can be used without restriction by expiration date. The nation should have a system that affirms whether and how wide differences there are between clinical trial data and actual use in medical fields,” Professor Lee said. “We should give two to five years of expiry rate and weed out those that cannot prove their values within the period from the reimbursement list.”

Professor Kim Heung-tae at National Cancer Center, who led the research, said, “Phase 3 clinical trials led by pharmaceuticals exclude inactive patients, aged patients and those with brain metastases. Once in the market, however, all patients used the drug. There are big gaps between real patients and clinical trial patients.”

He went on to say, “There is neither a system that can evaluate drug efficacy after their registration for reimbursement nor objective standards that evaluate such efficacy. And we don’t have a system that can weed out drugs after their registration, in a fair manner.”

Because the clinical trial data used for winning approvals and situations in medical fields are not always identical, regulators need to reevaluate them and readjust their policies ceaselessly based on Real World Evidence, Professor Kim pointed out.

‘Despite the need for the system, the real purpose seems to be lowering drug prices’ – drugmakers

The pharmaceutical industry, while agreeing on the need for the post-de-facto management of registered drugs, voiced concerns that the system itself could be used as a mechanism to lower medicine prices.

“We agree to introduce the post management system provided it is accompanied by the fast registration of new drugs, expanding the indications of new drugs and evaluating their values for improving patients’ access to medications,” said Kim So-eun, managing director of MSD Korea who also is a member of the Market Access Committee of Korea Research-based Pharma Industry Association. “However, we doubt whether and how the proposed system can be implemented without overlapping with the existing follow-up management system of drug prices. Besides, we would like the regulators to let us know in advance any concrete things additionally required because of the new system.”

If the proposed scheme becomes post-de-facto assessment for proving cost efficiency, it will end up as price evaluation. And the system becomes a follow-up assessment for the fiscal health of KHIS, it may deviate from its initial purpose, Kim noted.

Choi Jeong-in, an executive at Korea Pharmaceutical and Bio-pharma Manufacturers Association, also said, “The documents at KHIS point to the prince increasing trend of new drugs. The idea of the post management of registered medicines seems to have come against such a backdrop. I am worried the regulators are pushing ahead with it with the purpose.”

The health authorities are advised not to limit the use of reevaluation results in lowering drug prices or limiting payment but use them as guidelines for clinical treatments and reflect them on changing approved matters, Choi added.

‘Eliminate overlapping elements and work out acceptable model,’ ministry says
The Ministry of Health and Welfare showed a position it would work out a post-de-facto management system applicable to medical fields and acceptable by medical workers.

“Insurers are witnessing the rapid increase of uncertainty. So far, most drugs have been registered on the reimbursement list because of their proved safety and efficacy. Since the rapid approval system has been introduced, medical insurance has had to shoulder the burdens resulting from the registration of medicines with uncertain contents,” said Kwang Myeong-seop, director of the ministry’s Division of Pharmaceutical Benefits. “There are no other ways but the post management system that can evaluate the efficacy proved at entry stage can be applied to actual clinical fields.”

Park Young-mi, manager of the Drug Management Department at Health Insurance Review and Assessment Service, agreed, saying, “Researchers said there are no bases to weed out drugs once registered on the reimbursement list. However, possible exits should have more evident grounds than registration.”

She went on to say, “They talked about research results that showed the efficacy of drugs is less than those of clinical trials. If so, this is not a matter limited to health insurance. The Ministry of Food and Drug Safety needs to share part of the concerns.”