Thread by @das_seed

Phase 3 trial results for COVAXIN (a double-blind, randomised, placebo-controlled trial). Thread.

medrxiv.org/content/10.110… 2 July 2021.

1. Vaccine efficacy against

● Symptomatic COVID19+ve: 77.8% (95% CI: 65.2–86.4) w/ 130 cases (24 COVAXIN, 106 placebo)

● Severe symptomatic COVID-19+ve: 93·4% (57·1–99·8) w/ 16 cases (1 COVAXIN, 15 placebo)

● Symptomatic COVID19+ve in age 18–59 yrs: 79·4% (66–88·2) w/ 109 cases (19 COVAXIN, 90 placebo)

● Asymptomatic COVID19+ve: 63·6% (29🤔–82·4) w/ 47(?) cases (13 COVAXIN+33 placebo=46🤦)

2. Vaccine efficacy against symptomatic COVID19+ve

● B.1.617.2 (Delta): 65·2% (33·1–83·0) w/ 50 cases (13 COVAXIN, 37 placebo)

● B.1.617.1 (Kappa): 90·1% (30·4–99·8) w/ 11 cases (1 COVAXIN, 10 placebo)

3. Total 79 variants (VOIs or VOCs) detected in 130 cases analyzed for

vaccine efficacy. Among these 79 cases (18 COVAXIN, 61 placebo), 4 cases of severe COVID19+ve, all 4 of them in placebo.

4. Population enrolled in trial

● Placebo: 4254 ♀️, 8620 ♂️
COVAXIN: 4214 ♀️, 8665 ♂️

● At baseline (day 0): 213 COVID+ve, 7818 anti-SARS-CoV-2 IgG+ve.

● 15 deaths (5 COVAXIN, 10 placebo) in trial, none deemed related to COVAXIN or placebo:

5 deaths in COVAXIN: 1 cerebellar haemorrhage, 1 haemorrhagic stroke, 1 ovarian cancer w/ metasases, 1 sudden cardiac, 1 COVID19

10 deaths in placebo: 1 alcohol overdose, 1 myocardial

infarction, 1 cardiac arrest w/ hunderlying hypertension, 5 COVID19, 2 yet to be determined.

● Summary of AEs (Left pic)
● Incidences of solicited AEs after each dose (Right pic)

🤔In Safety, mentions

"2 related serious adverse events were reported among COVAXIN recipients"

but later in Discussion mentions

"one possibly related serious adverse event in COVAXIN group was a case of immune thrombocytic purpura that occurred 39 days after the 2nd dose in a participant who was SARS-CoV-2 seropositive at baseline, which resolved in four days."
🤦‍♀️🤦.

Total people (🧑‍🤝‍🧑): 12879🧑‍🤝‍🧑 (12879 COVAXIN, 12874 placebo)

All AEs: 3194🧑‍🤝‍🧑 (1597 COVAXIN, 1597 placebo)🤨

Unsolicited AEs: 1098🧑‍🤝‍🧑 (489 COVAXIN, 609 placebo)🤨🤨

SAEs: 99🧑‍🤝‍🧑 (39 COVAXIN, 60 placebo)🤨🤨

Any immediate AE (w/in 30 mins of jab): 35🧑‍🤝‍🧑 (12 COVAXIN, 23 placebo)🤨🤨

All Medically Attended AEs: 620🧑‍🤝‍🧑 (301 COVAXIN, 319 placebo)🤨🤨

AESIs: 46🧑‍🤝‍🧑 (23 COVAXIN, 23 placebo) 🤨🤨

[Looks like COVAXIN is safer than placebo🐒. Someone should calculate p-values.]

5. Puzzles on last jab timeline.

●On 7 Jan 2021, @BharatBiotech announced completion of

enrollment for Phase 3.

Paper on Phase 3 trial states that b/w 16 Nov 2020 & 7 Jan 2021, 25798 participants recruited & randomized.

First dose of IP was given to participant on day of randomization itself (day 0). COVAXIN needs 2 doses to be given, dosing interval of 28 days.

Therefore, if the last person was enrolled & randomized on 7 Jan 2021 then person would have got 1st dose on 7 Jan & next dose in 1st week of Feb itself.

However, on 9 June 2021, @RachesElla claimed that the last participant received the 2nd dose around mid-March. Why & how?🤔

6. Puzzles on conductance of trial in compliance w/ all ICH GCP guidelines.

For instances:

● Paper states regd at clinicaltrials.gov/ct2/show/NCT04… and "Volunteers were screened for eligibility based on their health status, includ. medical history, vital signs, &

physical examination results. Eligible participants provided signed & dated informed consent forms at enrolment"

In late Dec 2020 & early Jan 2021, huge misconduct in trial at Bhopal's site, People’s Hospital, came to light, see fmesinstitute.org/wp-content/upl…

Many illiterate people who were unaware of trials were recruited in name of "vaccine" against COVID19. As per protocol, these people shouldn't have been recruited as they couldn't give signed & dated consent form (we can forget about informed consent). Even medical conditions

were not considered.

An individual w/ ovarian cancer got enrolled in trial, who unfortunately died.

People's Univ, Bhopal is one of 14 sites out of 25 trial sites in Phase 3 whose PI is coauthor w/ team from BBIL, ICMR, ICMR-NIV, & a stat consultancy.😱

● Unsettling efficacy/safety analysis

a) 2nd interim analysis cut-off was 87 cases but due to COVID19 surge 127 cases were accrued & analyzed by 21 April 2021, efficacy estimate 78% (CI: 61–88) a/c to @BharatBiotech & @ICMRDELHI.

Target of 130 cases for final analysis. Twist

is that cut-off date for safety analysis is 17 May 2021.

Cases surging more rapidly during late April & early May (enormously), more cases must have been accrued in Phase 3 trial participants during this period than mere 3 added to already analyzed 127 cases.

What was actual

count of COVID19 disease among participants till 17 May is unknown. Paper gives no description of what actually "lost follow-ups" mean when contact/residence addresses are recorded during enrollment.

b) There's no info of how many deaths took place post 2-doses of IP. Did

efficacy analysis against severe COVID19+ve constituted deaths, required ICU, or standard of care hospitalization (w/ or w/o oxygen supply) in COVAXIN/placebo aren't clarified.

Though efficacy analysis against COVID19 mortality is secondary endpoint. This leaves a critical

question unanswered: were there no deaths after 2 weeks of 2nd dose of IP (COVAXIN or placebo)?

c) There's no explanation or discussion on as to why Unsolicited AEs, SAEs*, immediate AEs*, MMAEs were (*considerably) higher in placebo group than COVAXIN. What makes COVAXIN

have a better safety profile than placebo (Phosphate buffered saline w/ Algel). There's no mentioning of what adverse events of concern were seen. When there was no anaphylaxis recorded, what kind of immediate AEs were seen, assuming that healthy participants w/ consent enroll.