There has been a lot of discussion about the Progressive Disease (PD) number reported in an erroneous slide deck that was inadvertently uploaded on Monday, 25 May 2015, to the website of the Market Observation Post System (MOPS) at the Taipei Exchange (GreTai Securities Market). OBI Pharma (OBI) directly and thoroughly addressed this matter at its Annual General Meeting on Wednesday, 3 June 2015. Beginning 4 June, the news media in Taiwan began to publish incorrect and speculative articles that have even implied that clinical data was falsified. Integrity is an uncompromising commitment for all scientific researchers, and OBI emphasizes that its clinical trial operations have always met the most stringent global standards and have fully complied with the regulations.
For the record, OBI wishes to clarify the following:
According to the original OPT-822-001 Clinical Trial Protocol, when the number of subjects with progressive disease (PD number) reaches 142 people (as tabulated by the Central Review laboratory, or “Central Read”), then Interim Analysis may be conducted. The OPT-822-001 trial reached its target enrollment of 342 subjects in July 2014. In October 2014, OBI consulted with the Center for Drug Evaluation (CDE), who subsequently agreed to waive the Interim Analysis based on all the meeting reports of the OPT-822-001 trial’s Data Safety Monitoring Board (DSMB), which had already met 7 times up until then and had not reported any safety concerns. Consequently, on 4 Nov 2014, OBI submitted the 7th DSMB report to the Taiwan Food and Drug Administration (FDA) and received final approval for Protocol Version 9, which removed the Interim Analysis.
Last month, beginning 26 May 2015, OBI senior management participated in a series of overseas meetings to introduce the company to institutional investors given the recent and successful uplisting last March 2015. At 17:43 on 25 May 2015, the day before the overseas meetings, the company profile slide deck was uploaded to the MOPS website in compliance with regulations. It was later discovered that there were typographical errors on Slide 22 which concerned the results of the 8th DSMB meeting that happened on 10 Jan 2015. Before the trip, the slide indicated a total of 187 PD (as reported by the 40 clinical trial sites, or “Local Read”) reported at the 8th DSMB meeting. This number was updated to 229 PD (Local Read), which is the reported Local Read figure as of May 2015, in order to provide the latest information during the investor discussions. However, the date on the slide was not updated accordingly. This is the root of the confusion in the public and the media: that there seemed to be 229 PD as of 10 Jan 2015. On 26 May 2015 at 13:25, OBI uploaded a revised slide deck to the MOPS website, which did not have the incorrect Slide 22.
According to the OPT-822-001 Clinical Trial Protocol, when the PD number reaches 289 (Central Read), the unblinding of data may begin. The Economic Daily News newspaper in Taiwan reported that this investigational product has been tested on subjects for only around 10 months. In fact, the first patient of the trial was enrolled 4.5 years ago in January 2011. As of May 2015, the total PD number reported by the clinical trial sites (Local Read) was 229. OBI plans to convene an Expert Meeting in August 2015 to determine an appropriate time to unblind the data of the trial. The Economic Daily News article also stated, “若延長至一年，復發人數約120人即可 ”. OBI does not estimate or predict future PD numbers. The PD number is based on what is reported by the sites and the Central laboratory. This newspaper report is incorrect and not based on any evidence.
The above matters concern clinical trial expertise and have raised questions and discussions among shareholders, so OBI decided to take the opportunity to explain the necessary difference between PD reported by Local Read and PD reported by Central Read at the shareholder meeting; the difference is due to differences in physician judgement and timing.
There are two ways the PD number is reported in a clinical trial: one is the Local Read which is determined by each patient’s treating physicians, and the other is by medical imaging read by radiologist at the Central Review laboratory (Central Read). At the end of the trial, when all of the data is finalized, a discrepancy in PD number between Local Read and Central Read is generally seen.
The efficacy of the investigational product in a clinical trial should only be assessed by the results after the unblinding of the data. OBI Pharma’s research, planning, and operations continue to progress as usual. OBI will continue to comply with international clinical trial ethics and meet the regulatory standards, and disclose information in a fair and open way. The company remains confident that the OPT-822-001 meets the most stringent global standards for clinical trial conduct.